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0 | 95369245 | [
{
"id": "1",
"type": "title",
"text": [
"IL-2 gene expression and NF-kappa B activation through CD28 requires reactive oxygen production by 5-lipoxygenase."
],
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0,
114
]
]
},
{
"id": "2",
"type": "abstract",
"text": [
"Activation of the CD28 surface receptor provides a major costimulatory signal for T cell activation resulting in enhanced production of interleukin-2 (IL-2) and cell proliferation. In primary T lymphocytes we show that CD28 ligation leads to the rapid intracellular formation of reactive oxygen intermediates (ROIs) which are required for CD28-mediated activation of the NF-kappa B/CD28-responsive complex and IL-2 expression. Delineation of the CD28 signaling cascade was found to involve protein tyrosine kinase activity, followed by the activation of phospholipase A2 and 5-lipoxygenase. Our data suggest that lipoxygenase metabolites activate ROI formation which then induce IL-2 expression via NF-kappa B activation. These findings should be useful for therapeutic strategies and the development of immunosuppressants targeting the CD28 costimulatory pathway."
],
"offsets": [
[
115,
979
]
]
}
] | [
{
"id": "3",
"type": "other_name",
"text": [
"IL-2 gene expression"
],
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[
0,
20
]
],
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},
{
"id": "4",
"type": "DNA_domain_or_region",
"text": [
"IL-2 gene"
],
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[
0,
9
]
],
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},
{
"id": "5",
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"NF-kappa B activation"
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25,
46
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{
"id": "6",
"type": "protein_molecule",
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"NF-kappa B"
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25,
35
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{
"id": "7",
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"CD28"
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{
"id": "8",
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"5-lipoxygenase"
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99,
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{
"id": "9",
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"CD28 surface receptor"
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133,
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],
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{
"id": "10",
"type": "protein_molecule",
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"CD28"
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{
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"T cell activation"
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197,
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{
"id": "12",
"type": "protein_molecule",
"text": [
"interleukin-2"
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{
"id": "13",
"type": "protein_molecule",
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"IL-2"
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{
"id": "14",
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"text": [
"cell proliferation"
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],
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},
{
"id": "15",
"type": "cell_type",
"text": [
"primary T lymphocytes"
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{
"id": "16",
"type": "protein_molecule",
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"CD28"
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{
"id": "17",
"type": "inorganic",
"text": [
"reactive oxygen intermediates"
],
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394,
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]
],
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},
{
"id": "18",
"type": "inorganic",
"text": [
"ROIs"
],
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425,
429
]
],
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},
{
"id": "19",
"type": "other_name",
"text": [
"CD28-mediated activation"
],
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],
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},
{
"id": "20",
"type": "protein_molecule",
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"CD28"
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{
"id": "21",
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"NF-kappa B"
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{
"id": "22",
"type": "protein_complex",
"text": [
"CD28-responsive complex"
],
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{
"id": "23",
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"CD28"
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{
"id": "24",
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"text": [
"IL-2 expression"
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{
"id": "25",
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{
"id": "26",
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"text": [
"CD28 signaling cascade"
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{
"id": "27",
"type": "protein_molecule",
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"CD28"
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{
"id": "28",
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"protein tyrosine kinase activity"
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605,
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{
"id": "29",
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"protein tyrosine kinase"
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},
{
"id": "30",
"type": "protein_molecule",
"text": [
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{
"id": "31",
"type": "protein_molecule",
"text": [
"5-lipoxygenase"
],
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690,
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{
"id": "32",
"type": "protein_family_or_group",
"text": [
"lipoxygenase metabolites"
],
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],
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},
{
"id": "33",
"type": "protein_molecule",
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"lipoxygenase"
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},
{
"id": "34",
"type": "other_name",
"text": [
"ROI formation"
],
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762,
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]
],
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},
{
"id": "35",
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"ROI"
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762,
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]
],
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},
{
"id": "36",
"type": "protein_molecule",
"text": [
"IL-2"
],
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794,
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]
],
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},
{
"id": "37",
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"text": [
"NF-kappa B activation"
],
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814,
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]
],
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},
{
"id": "38",
"type": "protein_molecule",
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"NF-kappa B"
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],
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},
{
"id": "39",
"type": "other_name",
"text": [
"therapeutic strategies"
],
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873,
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]
],
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},
{
"id": "40",
"type": "other_name",
"text": [
"immunosuppressants"
],
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919,
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]
],
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},
{
"id": "41",
"type": "other_name",
"text": [
"CD28 costimulatory pathway"
],
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[
952,
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]
],
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},
{
"id": "42",
"type": "protein_molecule",
"text": [
"CD28"
],
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[
952,
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]
],
"normalized": []
}
] | [] | [] | [] |
43 | 95333264 | [
{
"id": "44",
"type": "title",
"text": [
"The peri-kappa B site mediates human immunodeficiency virus type 2 enhancer activation in monocytes but not in T cells."
],
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[
0,
119
]
]
},
{
"id": "45",
"type": "abstract",
"text": [
"Human immunodeficiency virus type 2 (HIV-2), like HIV-1, causes AIDS and is associated with AIDS cases primarily in West Africa. HIV-1 and HIV-2 display significant differences in nucleic acid sequence and in the natural history of clinical disease. Consistent with these differences, we have previously demonstrated that the enhancer/promoter region of HIV-2 functions quite differently from that of HIV-1. Whereas activation of the HIV-1 enhancer following T-cell stimulation is mediated largely through binding of the transcription factor NF-kappa B to two adjacent kappa B sites in the HIV-1 long terminal repeat, activation of the HIV-2 enhancer in monocytes and T cells is dependent on four cis-acting elements: a single kappa B site, two purine-rich binding sites, PuB1 and PuB2, and a pets site. We have now identified a novel cis-acting element within the HIV-2 enhancer, immediately upstream of the kappa B site, designated peri-kappa B. This site is conserved among isolates of HIV-2 and the closely related simian immunodeficiency virus, and transfection assays show this site to mediate HIV-2 enhancer activation following stimulation of monocytic but not T-cell lines. This is the first description of an HIV-2 enhancer element which displays such monocyte specificity, and no comparable enhancer element has been clearly defined for HIV-1. While a nuclear factor(s) from both peripheral blood monocytes and T cells binds the peri-kappa B site, electrophoretic mobility shift assays suggest that either a different protein binds to this site in monocytes versus T cells or that the protein recognizing this enhancer element undergoes differential modification in monocytes and T cells, thus supporting the transfection data. Further, while specific constitutive binding to the peri-kappa B site is seen in monocytes, stimulation with phorbol esters induces additional, specific binding. Understanding the monocyte-specific function of the peri-kappa B factor may ultimately provide insight into the different role monocytes and T cells play in HIV pathogenesis."
],
"offsets": [
[
120,
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]
]
}
] | [
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4,
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"human immunodeficiency virus type 2 enhancer activation"
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"T cells"
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},
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{
"id": "106",
"type": "DNA_domain_or_region",
"text": [
"enhancer element"
],
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[
1741,
1757
]
],
"normalized": []
},
{
"id": "107",
"type": "other_name",
"text": [
"differential modification"
],
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[
1768,
1793
]
],
"normalized": []
},
{
"id": "108",
"type": "cell_type",
"text": [
"monocytes"
],
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]
],
"normalized": []
},
{
"id": "109",
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"text": [
"T cells"
],
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1811,
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]
],
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},
{
"id": "110",
"type": "DNA_domain_or_region",
"text": [
"peri-kappa B site"
],
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]
],
"normalized": []
},
{
"id": "111",
"type": "cell_type",
"text": [
"monocytes"
],
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[
1940,
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]
],
"normalized": []
},
{
"id": "112",
"type": "other_organic_compound",
"text": [
"phorbol esters"
],
"offsets": [
[
1968,
1982
]
],
"normalized": []
},
{
"id": "113",
"type": "other_name",
"text": [
"monocyte-specific function"
],
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[
2039,
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]
],
"normalized": []
},
{
"id": "114",
"type": "protein_molecule",
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],
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]
],
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},
{
"id": "115",
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"monocytes"
],
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]
],
"normalized": []
},
{
"id": "116",
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"T cells"
],
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2162,
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]
],
"normalized": []
},
{
"id": "117",
"type": "other_name",
"text": [
"HIV pathogenesis"
],
"offsets": [
[
2178,
2194
]
],
"normalized": []
}
] | [] | [] | [] |
118 | 95343554 | [
{
"id": "119",
"type": "title",
"text": [
"E1A gene expression induces susceptibility to killing by NK cells following immortalization but not adenovirus infection of human cells."
],
"offsets": [
[
0,
136
]
]
},
{
"id": "120",
"type": "abstract",
"text": [
"Adenovirus (Ad) infection and E1A transfection were used to model changes in susceptibility to NK cell killing caused by transient vs stable E1A expression in human cells. Only stably transfected target cells exhibited cytolytic susceptibility, despite expression of equivalent levels of E1A proteins in Ad-infected targets. The inability of E1A gene products to induce cytolytic susceptibility during infection was not explained by an inhibitory effect of viral infection on otherwise susceptible target cells or by viral gene effects on class I MHC antigen expression on target cells. This differential effect of E1A expression on the cytolytic phenotypes of infected and stably transfected human cells suggests that human NK cells provide an effective immunologic barrier against the in vivo survival and neoplastic progression of E1A-immortalized cells that may emerge from the reservoir of persistently infected cells in the human host."
],
"offsets": [
[
137,
1078
]
]
}
] | [
{
"id": "121",
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"E1A gene expression"
],
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[
0,
19
]
],
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},
{
"id": "122",
"type": "DNA_domain_or_region",
"text": [
"E1A gene"
],
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[
0,
8
]
],
"normalized": []
},
{
"id": "123",
"type": "cell_type",
"text": [
"NK cells"
],
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[
57,
65
]
],
"normalized": []
},
{
"id": "124",
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"adenovirus infection"
],
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100,
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]
],
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},
{
"id": "125",
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"adenovirus"
],
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100,
110
]
],
"normalized": []
},
{
"id": "126",
"type": "cell_type",
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"human cells"
],
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124,
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]
],
"normalized": []
},
{
"id": "127",
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"text": [
"Adenovirus (Ad) infection"
],
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137,
162
]
],
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},
{
"id": "128",
"type": "virus",
"text": [
"Adenovirus"
],
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137,
147
]
],
"normalized": []
},
{
"id": "129",
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"E1A transfection"
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167,
183
]
],
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},
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"id": "130",
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"E1A"
],
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167,
170
]
],
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},
{
"id": "131",
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"text": [
"NK cell killing"
],
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232,
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]
],
"normalized": []
},
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"id": "132",
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278,
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],
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},
{
"id": "133",
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"E1A"
],
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]
],
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},
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"id": "134",
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"text": [
"human cells"
],
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[
296,
307
]
],
"normalized": []
},
{
"id": "135",
"type": "cell_line",
"text": [
"transfected target cells"
],
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321,
345
]
],
"normalized": []
},
{
"id": "136",
"type": "protein_family_or_group",
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"E1A proteins"
],
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425,
437
]
],
"normalized": []
},
{
"id": "137",
"type": "cell_line",
"text": [
"Ad-infected targets"
],
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441,
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],
"normalized": []
},
{
"id": "138",
"type": "DNA_domain_or_region",
"text": [
"E1A gene"
],
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[
479,
487
]
],
"normalized": []
},
{
"id": "139",
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"cytolytic susceptibility"
],
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507,
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]
],
"normalized": []
},
{
"id": "140",
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"target cells"
],
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[
635,
647
]
],
"normalized": []
},
{
"id": "141",
"type": "DNA_domain_or_region",
"text": [
"viral gene"
],
"offsets": [
[
654,
664
]
],
"normalized": []
},
{
"id": "142",
"type": "other_name",
"text": [
"class I MHC antigen expression"
],
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[
676,
706
]
],
"normalized": []
},
{
"id": "143",
"type": "protein_family_or_group",
"text": [
"class I MHC antigen"
],
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676,
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]
],
"normalized": []
},
{
"id": "144",
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"text": [
"target cells"
],
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]
],
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},
{
"id": "145",
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],
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752,
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],
"normalized": []
},
{
"id": "146",
"type": "protein_molecule",
"text": [
"E1A"
],
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752,
755
]
],
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},
{
"id": "147",
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"text": [
"human cells"
],
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[
830,
841
]
],
"normalized": []
},
{
"id": "148",
"type": "cell_type",
"text": [
"human NK cells"
],
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[
856,
870
]
],
"normalized": []
},
{
"id": "149",
"type": "cell_type",
"text": [
"NK cells"
],
"offsets": [
[
862,
870
]
],
"normalized": []
},
{
"id": "150",
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"text": [
"neoplastic progression"
],
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[
945,
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]
],
"normalized": []
},
{
"id": "151",
"type": "cell_line",
"text": [
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],
"offsets": [
[
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]
],
"normalized": []
},
{
"id": "152",
"type": "cell_type",
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"persistently infected cells"
],
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[
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]
],
"normalized": []
},
{
"id": "153",
"type": "multi_cell",
"text": [
"human host"
],
"offsets": [
[
1067,
1077
]
],
"normalized": []
}
] | [] | [] | [] |
154 | 95347379 | [
{
"id": "155",
"type": "title",
"text": [
"Distinct signaling properties identify functionally different CD4 epitopes."
],
"offsets": [
[
0,
75
]
]
},
{
"id": "156",
"type": "abstract",
"text": [
"The CD4 coreceptor interacts with non-polymorphic regions of major histocompatibility complex class II molecules on antigen-presenting cells and contributes to T cell activation. We have investigated the effect of CD4 triggering on T cell activating signals in a lymphoma model using monoclonal antibodies (mAb) which recognize different CD4 epitopes. We demonstrate that CD4 triggering delivers signals capable of activating the NF-AT transcription factor which is required for interleukin-2 gene expression. Whereas different anti-CD4 mAb or HIV-1 gp120 could all trigger activation of the protein tyrosine kinases p56lck and p59fyn and phosphorylation of the Shc adaptor protein, which mediates signals to Ras, they differed significantly in their ability to activate NF-AT. Lack of full activation of NF-AT could be correlated to a dramatically reduced capacity to induce calcium flux and could be complemented with a calcium ionophore. The results identify functionally distinct epitopes on the CD4 coreceptor involved in activation of the Ras/protein kinase C and calcium pathways."
],
"offsets": [
[
76,
1163
]
]
}
] | [
{
"id": "157",
"type": "protein_family_or_group",
"text": [
"CD4 epitopes"
],
"offsets": [
[
62,
74
]
],
"normalized": []
},
{
"id": "158",
"type": "protein_molecule",
"text": [
"CD4 coreceptor"
],
"offsets": [
[
80,
94
]
],
"normalized": []
},
{
"id": "159",
"type": "protein_domain_or_region",
"text": [
"non-polymorphic regions"
],
"offsets": [
[
110,
133
]
],
"normalized": []
},
{
"id": "160",
"type": "protein_family_or_group",
"text": [
"major histocompatibility complex class II molecules"
],
"offsets": [
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137,
188
]
],
"normalized": []
},
{
"id": "161",
"type": "cell_type",
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"antigen-presenting cells"
],
"offsets": [
[
192,
216
]
],
"normalized": []
},
{
"id": "162",
"type": "other_name",
"text": [
"T cell activation"
],
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236,
253
]
],
"normalized": []
},
{
"id": "163",
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"text": [
"CD4 triggering"
],
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290,
304
]
],
"normalized": []
},
{
"id": "164",
"type": "protein_molecule",
"text": [
"CD4"
],
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[
290,
293
]
],
"normalized": []
},
{
"id": "165",
"type": "other_name",
"text": [
"T cell activating signals"
],
"offsets": [
[
308,
333
]
],
"normalized": []
},
{
"id": "166",
"type": "other_name",
"text": [
"lymphoma model"
],
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[
339,
353
]
],
"normalized": []
},
{
"id": "167",
"type": "protein_family_or_group",
"text": [
"monoclonal antibodies"
],
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360,
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]
],
"normalized": []
},
{
"id": "168",
"type": "protein_domain_or_region",
"text": [
"mAb"
],
"offsets": [
[
383,
386
]
],
"normalized": []
},
{
"id": "169",
"type": "protein_family_or_group",
"text": [
"CD4 epitopes"
],
"offsets": [
[
414,
426
]
],
"normalized": []
},
{
"id": "170",
"type": "other_name",
"text": [
"CD4 triggering"
],
"offsets": [
[
448,
462
]
],
"normalized": []
},
{
"id": "171",
"type": "protein_molecule",
"text": [
"CD4"
],
"offsets": [
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448,
451
]
],
"normalized": []
},
{
"id": "172",
"type": "protein_molecule",
"text": [
"NF-AT transcription factor"
],
"offsets": [
[
506,
532
]
],
"normalized": []
},
{
"id": "173",
"type": "other_name",
"text": [
"interleukin-2 gene expression"
],
"offsets": [
[
555,
584
]
],
"normalized": []
},
{
"id": "174",
"type": "protein_molecule",
"text": [
"interleukin-2"
],
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555,
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]
],
"normalized": []
},
{
"id": "175",
"type": "protein_family_or_group",
"text": [
"anti-CD4 mAb"
],
"offsets": [
[
604,
616
]
],
"normalized": []
},
{
"id": "176",
"type": "protein_molecule",
"text": [
"HIV-1 gp120"
],
"offsets": [
[
620,
631
]
],
"normalized": []
},
{
"id": "177",
"type": "virus",
"text": [
"HIV-1"
],
"offsets": [
[
620,
625
]
],
"normalized": []
},
{
"id": "178",
"type": "protein_family_or_group",
"text": [
"protein tyrosine kinases"
],
"offsets": [
[
668,
692
]
],
"normalized": []
},
{
"id": "179",
"type": "protein_molecule",
"text": [
"p56lck"
],
"offsets": [
[
693,
699
]
],
"normalized": []
},
{
"id": "180",
"type": "protein_molecule",
"text": [
"p59fyn"
],
"offsets": [
[
704,
710
]
],
"normalized": []
},
{
"id": "181",
"type": "protein_molecule",
"text": [
"Shc adaptor protein"
],
"offsets": [
[
738,
757
]
],
"normalized": []
},
{
"id": "182",
"type": "protein_family_or_group",
"text": [
"Ras"
],
"offsets": [
[
785,
788
]
],
"normalized": []
},
{
"id": "183",
"type": "protein_molecule",
"text": [
"NF-AT"
],
"offsets": [
[
847,
852
]
],
"normalized": []
},
{
"id": "184",
"type": "protein_molecule",
"text": [
"NF-AT"
],
"offsets": [
[
881,
886
]
],
"normalized": []
},
{
"id": "185",
"type": "other_name",
"text": [
"calcium flux"
],
"offsets": [
[
952,
964
]
],
"normalized": []
},
{
"id": "186",
"type": "atom",
"text": [
"calcium"
],
"offsets": [
[
952,
959
]
],
"normalized": []
},
{
"id": "187",
"type": "other_organic_compound",
"text": [
"calcium ionophore"
],
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[
998,
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]
],
"normalized": []
},
{
"id": "188",
"type": "protein_family_or_group",
"text": [
"epitopes"
],
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]
],
"normalized": []
},
{
"id": "189",
"type": "protein_molecule",
"text": [
"CD4 coreceptor"
],
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[
1076,
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]
],
"normalized": []
},
{
"id": "190",
"type": "other_name",
"text": [
"Ras/protein kinase C and calcium pathways"
],
"offsets": [
[
1121,
1162
]
],
"normalized": []
},
{
"id": "191",
"type": "protein_molecule",
"text": [
"Ras/protein kinase C"
],
"offsets": [
[
1121,
1141
]
],
"normalized": []
},
{
"id": "192",
"type": "other_name",
"text": [
"Ras/protein kinase C"
],
"offsets": [
[
1121,
1141
]
],
"normalized": []
},
{
"id": "193",
"type": "protein_molecule",
"text": [
"Ras"
],
"offsets": [
[
1121,
1124
]
],
"normalized": []
},
{
"id": "194",
"type": "protein_molecule",
"text": [
"/protein kinase C"
],
"offsets": [
[
1124,
1141
]
],
"normalized": []
},
{
"id": "195",
"type": "other_name",
"text": [
"calcium pathways"
],
"offsets": [
[
1146,
1162
]
],
"normalized": []
}
] | [] | [] | [] |
196 | 95280913 | [
{
"id": "197",
"type": "title",
"text": [
"Ligand-dependent repression of the erythroid transcription factor GATA-1 by the estrogen receptor."
],
"offsets": [
[
0,
98
]
]
},
{
"id": "198",
"type": "abstract",
"text": [
"High-dose estrogen administration induces anemia in mammals. In chickens, estrogens stimulate outgrowth of bone marrow-derived erythroid progenitor cells and delay their maturation. This delay is associated with down-regulation of many erythroid cell-specific genes, including alpha- and beta-globin, band 3, band 4.1, and the erythroid cell-specific histone H5. We show here that estrogens also reduce the number of erythroid progenitor cells in primary human bone marrow cultures. To address potential mechanisms by which estrogens suppress erythropoiesis, we have examined their effects on GATA-1, an erythroid transcription factor that participates in the regulation of the majority of erythroid cell-specific genes and is necessary for full maturation of erythrocytes. We demonstrate that the transcriptional activity of GATA-1 is strongly repressed by the estrogen receptor (ER) in a ligand-dependent manner and that this repression is reversible in the presence of 4-hydroxytamoxifen. ER-mediated repression of GATA-1 activity occurs on an artificial promoter containing a single GATA-binding site, as well as in the context of an intact promoter which is normally regulated by GATA-1. GATA-1 and ER bind to each other in vitro in the absence of DNA. In coimmunoprecipitation experiments using transfected COS cells, GATA-1 and ER associate in a ligand-dependent manner. Mapping experiments indicate that GATA-1 and the ER form at least two contacts, which involve the finger region and the N-terminal activation domain of GATA-1. We speculate that estrogens exert effects on erythropoiesis by modulating GATA-1 activity through protein-protein interaction with the ER. (ABSTRACT TRUNCATED AT 250 WORDS)"
],
"offsets": [
[
99,
1809
]
]
}
] | [
{
"id": "199",
"type": "other_name",
"text": [
"Ligand-dependent repression"
],
"offsets": [
[
0,
27
]
],
"normalized": []
},
{
"id": "200",
"type": "protein_family_or_group",
"text": [
"erythroid transcription factor"
],
"offsets": [
[
35,
65
]
],
"normalized": []
},
{
"id": "201",
"type": "protein_molecule",
"text": [
"GATA-1"
],
"offsets": [
[
66,
72
]
],
"normalized": []
},
{
"id": "202",
"type": "protein_family_or_group",
"text": [
"estrogen receptor"
],
"offsets": [
[
80,
97
]
],
"normalized": []
},
{
"id": "203",
"type": "other_name",
"text": [
"High-dose estrogen administration"
],
"offsets": [
[
99,
132
]
],
"normalized": []
},
{
"id": "204",
"type": "other_name",
"text": [
"anemia"
],
"offsets": [
[
141,
147
]
],
"normalized": []
},
{
"id": "205",
"type": "multi_cell",
"text": [
"mammals"
],
"offsets": [
[
151,
158
]
],
"normalized": []
},
{
"id": "206",
"type": "cell_type",
"text": [
"bone marrow-derived erythroid progenitor cells"
],
"offsets": [
[
206,
252
]
],
"normalized": []
},
{
"id": "207",
"type": "other_name",
"text": [
"maturation"
],
"offsets": [
[
269,
279
]
],
"normalized": []
},
{
"id": "208",
"type": "other_name",
"text": [
"down-regulation"
],
"offsets": [
[
311,
326
]
],
"normalized": []
},
{
"id": "209",
"type": "DNA_family_or_group",
"text": [
"erythroid cell-specific genes"
],
"offsets": [
[
335,
364
]
],
"normalized": []
},
{
"id": "210",
"type": "(AND DNA_domain_or_region DNA_domain_or_region)",
"text": [
"alpha- and beta-globin"
],
"offsets": [
[
376,
398
]
],
"normalized": []
},
{
"id": "211",
"type": "",
"text": [
"alpha-"
],
"offsets": [
[
376,
382
]
],
"normalized": []
},
{
"id": "212",
"type": "",
"text": [
"beta-"
],
"offsets": [
[
387,
392
]
],
"normalized": []
},
{
"id": "213",
"type": "",
"text": [
"globin"
],
"offsets": [
[
392,
398
]
],
"normalized": []
},
{
"id": "214",
"type": "DNA_N/A",
"text": [
"band 3"
],
"offsets": [
[
400,
406
]
],
"normalized": []
},
{
"id": "215",
"type": "DNA_N/A",
"text": [
"band 4.1"
],
"offsets": [
[
408,
416
]
],
"normalized": []
},
{
"id": "216",
"type": "protein_molecule",
"text": [
"erythroid cell-specific histone"
],
"offsets": [
[
426,
457
]
],
"normalized": []
},
{
"id": "217",
"type": "protein_molecule",
"text": [
"H5"
],
"offsets": [
[
458,
460
]
],
"normalized": []
},
{
"id": "218",
"type": "cell_type",
"text": [
"erythroid progenitor cells"
],
"offsets": [
[
516,
542
]
],
"normalized": []
},
{
"id": "219",
"type": "cell_line",
"text": [
"primary human bone marrow cultures"
],
"offsets": [
[
546,
580
]
],
"normalized": []
},
{
"id": "220",
"type": "lipid",
"text": [
"estrogens"
],
"offsets": [
[
623,
632
]
],
"normalized": []
},
{
"id": "221",
"type": "other_name",
"text": [
"erythropoiesis"
],
"offsets": [
[
642,
656
]
],
"normalized": []
},
{
"id": "222",
"type": "protein_molecule",
"text": [
"GATA-1"
],
"offsets": [
[
692,
698
]
],
"normalized": []
},
{
"id": "223",
"type": "protein_family_or_group",
"text": [
"erythroid transcription factor"
],
"offsets": [
[
703,
733
]
],
"normalized": []
},
{
"id": "224",
"type": "DNA_domain_or_region",
"text": [
"erythroid cell-specific genes"
],
"offsets": [
[
789,
818
]
],
"normalized": []
},
{
"id": "225",
"type": "cell_type",
"text": [
"erythrocytes"
],
"offsets": [
[
859,
871
]
],
"normalized": []
},
{
"id": "226",
"type": "other_name",
"text": [
"transcriptional activity"
],
"offsets": [
[
897,
921
]
],
"normalized": []
},
{
"id": "227",
"type": "protein_molecule",
"text": [
"GATA-1"
],
"offsets": [
[
925,
931
]
],
"normalized": []
},
{
"id": "228",
"type": "protein_family_or_group",
"text": [
"estrogen receptor"
],
"offsets": [
[
961,
978
]
],
"normalized": []
},
{
"id": "229",
"type": "protein_family_or_group",
"text": [
"ER"
],
"offsets": [
[
980,
982
]
],
"normalized": []
},
{
"id": "230",
"type": "other_name",
"text": [
"repression"
],
"offsets": [
[
1027,
1037
]
],
"normalized": []
},
{
"id": "231",
"type": "other_organic_compound",
"text": [
"4-hydroxytamoxifen"
],
"offsets": [
[
1071,
1089
]
],
"normalized": []
},
{
"id": "232",
"type": "other_name",
"text": [
"ER-mediated repression"
],
"offsets": [
[
1091,
1113
]
],
"normalized": []
},
{
"id": "233",
"type": "protein_family_or_group",
"text": [
"ER"
],
"offsets": [
[
1091,
1093
]
],
"normalized": []
},
{
"id": "234",
"type": "other_name",
"text": [
"GATA-1 activity"
],
"offsets": [
[
1117,
1132
]
],
"normalized": []
},
{
"id": "235",
"type": "protein_molecule",
"text": [
"GATA-1"
],
"offsets": [
[
1117,
1123
]
],
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},
{
"id": "236",
"type": "DNA_molecule",
"text": [
"artificial promoter"
],
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[
1146,
1165
]
],
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},
{
"id": "237",
"type": "DNA_domain_or_region",
"text": [
"GATA-binding site"
],
"offsets": [
[
1186,
1203
]
],
"normalized": []
},
{
"id": "238",
"type": "DNA_domain_or_region",
"text": [
"intact promoter"
],
"offsets": [
[
1237,
1252
]
],
"normalized": []
},
{
"id": "239",
"type": "protein_molecule",
"text": [
"GATA-1"
],
"offsets": [
[
1284,
1290
]
],
"normalized": []
},
{
"id": "240",
"type": "protein_molecule",
"text": [
"GATA-1"
],
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[
1292,
1298
]
],
"normalized": []
},
{
"id": "241",
"type": "protein_family_or_group",
"text": [
"ER"
],
"offsets": [
[
1303,
1305
]
],
"normalized": []
},
{
"id": "242",
"type": "other_name",
"text": [
"coimmunoprecipitation experiments"
],
"offsets": [
[
1360,
1393
]
],
"normalized": []
},
{
"id": "243",
"type": "cell_line",
"text": [
"COS cells"
],
"offsets": [
[
1412,
1421
]
],
"normalized": []
},
{
"id": "244",
"type": "protein_molecule",
"text": [
"GATA-1"
],
"offsets": [
[
1423,
1429
]
],
"normalized": []
},
{
"id": "245",
"type": "protein_family_or_group",
"text": [
"ER"
],
"offsets": [
[
1434,
1436
]
],
"normalized": []
},
{
"id": "246",
"type": "other_name",
"text": [
"ligand-dependent manner"
],
"offsets": [
[
1452,
1475
]
],
"normalized": []
},
{
"id": "247",
"type": "protein_molecule",
"text": [
"GATA-1"
],
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[
1511,
1517
]
],
"normalized": []
},
{
"id": "248",
"type": "protein_family_or_group",
"text": [
"ER"
],
"offsets": [
[
1526,
1528
]
],
"normalized": []
},
{
"id": "249",
"type": "protein_domain_or_region",
"text": [
"N-terminal activation domain"
],
"offsets": [
[
1597,
1625
]
],
"normalized": []
},
{
"id": "250",
"type": "protein_molecule",
"text": [
"GATA-1"
],
"offsets": [
[
1629,
1635
]
],
"normalized": []
},
{
"id": "251",
"type": "lipid",
"text": [
"estrogens"
],
"offsets": [
[
1655,
1664
]
],
"normalized": []
},
{
"id": "252",
"type": "other_name",
"text": [
"erythropoiesis"
],
"offsets": [
[
1682,
1696
]
],
"normalized": []
},
{
"id": "253",
"type": "other_name",
"text": [
"GATA-1 activity"
],
"offsets": [
[
1711,
1726
]
],
"normalized": []
},
{
"id": "254",
"type": "protein_molecule",
"text": [
"GATA-1"
],
"offsets": [
[
1711,
1717
]
],
"normalized": []
},
{
"id": "255",
"type": "other_name",
"text": [
"protein-protein interaction"
],
"offsets": [
[
1735,
1762
]
],
"normalized": []
},
{
"id": "256",
"type": "protein_family_or_group",
"text": [
"ER"
],
"offsets": [
[
1772,
1774
]
],
"normalized": []
}
] | [] | [] | [] |
257 | 95256242 | [
{
"id": "258",
"type": "title",
"text": [
"Mouse interleukin-2 receptor alpha gene expression. Interleukin-1 and interleukin-2 control transcription via distinct cis-acting elements."
],
"offsets": [
[
0,
139
]
]
},
{
"id": "259",
"type": "abstract",
"text": [
"We have shown that interleukin-1 (IL-1) and IL-2 control IL-2 receptor alpha (IL-2R alpha) gene transcription in CD4-CD8- murine T lymphocyte precursors. Here we map the cis-acting elements that mediate interleukin responsiveness of the mouse IL-2R alpha gene using a thymic lymphoma-derived hybridoma (PC60). The transcriptional response of the IL-2R alpha gene to stimulation by IL-1 + IL-2 is biphasic. IL-1 induces a rapid, protein synthesis-independent appearance of IL-2R alpha mRNA that is blocked by inhibitors of NF-kappa B activation. It also primes cells to become IL-2 responsive and thereby prepares the second phase, in which IL-2 induces a 100-fold further increase in IL-2R alpha transcripts. Transient transfection experiments show that several elements in the promoter-proximal region of the IL-2R alpha gene contribute to IL-1 responsiveness, most importantly an NF-kappa B site conserved in the human and mouse gene. IL-2 responsiveness, on the other hand, depends on a 78-nucleotide segment 1.3 kilobases upstream of the major transcription start site. This segment functions as an IL-2-inducible enhancer and lies within a region that becomes DNase I hypersensitive in normal T cells in which IL-2R alpha expression has been induced. IL-2 responsiveness requires three distinct elements within the enhancer. Two of these are potential binding sites for STAT proteins."
],
"offsets": [
[
140,
1529
]
]
}
] | [
{
"id": "260",
"type": "other_name",
"text": [
"Mouse interleukin-2 receptor alpha gene expression"
],
"offsets": [
[
0,
50
]
],
"normalized": []
},
{
"id": "261",
"type": "DNA_domain_or_region",
"text": [
"Mouse interleukin-2 receptor alpha gene"
],
"offsets": [
[
0,
39
]
],
"normalized": []
},
{
"id": "262",
"type": "protein_molecule",
"text": [
"interleukin-2"
],
"offsets": [
[
6,
19
]
],
"normalized": []
},
{
"id": "263",
"type": "protein_molecule",
"text": [
"Interleukin-1"
],
"offsets": [
[
52,
65
]
],
"normalized": []
},
{
"id": "264",
"type": "protein_molecule",
"text": [
"interleukin-2"
],
"offsets": [
[
70,
83
]
],
"normalized": []
},
{
"id": "265",
"type": "DNA_family_or_group",
"text": [
"cis-acting elements"
],
"offsets": [
[
119,
138
]
],
"normalized": []
},
{
"id": "266",
"type": "protein_molecule",
"text": [
"interleukin-1"
],
"offsets": [
[
159,
172
]
],
"normalized": []
},
{
"id": "267",
"type": "protein_molecule",
"text": [
"IL-1"
],
"offsets": [
[
174,
178
]
],
"normalized": []
},
{
"id": "268",
"type": "protein_molecule",
"text": [
"IL-2"
],
"offsets": [
[
184,
188
]
],
"normalized": []
},
{
"id": "269",
"type": "other_name",
"text": [
"IL-2 receptor alpha (IL-2R alpha) gene transcription"
],
"offsets": [
[
197,
249
]
],
"normalized": []
},
{
"id": "270",
"type": "DNA_domain_or_region",
"text": [
"IL-2 receptor alpha (IL-2R alpha) gene"
],
"offsets": [
[
197,
235
]
],
"normalized": []
},
{
"id": "271",
"type": "protein_molecule",
"text": [
"IL-2 receptor alpha"
],
"offsets": [
[
197,
216
]
],
"normalized": []
},
{
"id": "272",
"type": "protein_molecule",
"text": [
"IL-2R alpha"
],
"offsets": [
[
218,
229
]
],
"normalized": []
},
{
"id": "273",
"type": "cell_line",
"text": [
"CD4-CD8- murine T lymphocyte precursors"
],
"offsets": [
[
253,
292
]
],
"normalized": []
},
{
"id": "274",
"type": "DNA_family_or_group",
"text": [
"cis-acting elements"
],
"offsets": [
[
310,
329
]
],
"normalized": []
},
{
"id": "275",
"type": "DNA_domain_or_region",
"text": [
"mouse IL-2R alpha gene"
],
"offsets": [
[
377,
399
]
],
"normalized": []
},
{
"id": "276",
"type": "protein_molecule",
"text": [
"mouse IL-2R alpha"
],
"offsets": [
[
377,
394
]
],
"normalized": []
},
{
"id": "277",
"type": "cell_line",
"text": [
"thymic lymphoma-derived hybridoma"
],
"offsets": [
[
408,
441
]
],
"normalized": []
},
{
"id": "278",
"type": "cell_line",
"text": [
"PC60"
],
"offsets": [
[
443,
447
]
],
"normalized": []
},
{
"id": "279",
"type": "DNA_domain_or_region",
"text": [
"IL-2R alpha gene"
],
"offsets": [
[
486,
502
]
],
"normalized": []
},
{
"id": "280",
"type": "protein_molecule",
"text": [
"IL-1"
],
"offsets": [
[
521,
525
]
],
"normalized": []
},
{
"id": "281",
"type": "protein_molecule",
"text": [
"IL-2"
],
"offsets": [
[
486,
490
]
],
"normalized": []
},
{
"id": "282",
"type": "protein_molecule",
"text": [
"IL-1"
],
"offsets": [
[
546,
550
]
],
"normalized": []
},
{
"id": "283",
"type": "other_name",
"text": [
"protein synthesis-independent appearance"
],
"offsets": [
[
568,
608
]
],
"normalized": []
},
{
"id": "284",
"type": "RNA_molecule",
"text": [
"IL-2R alpha mRNA"
],
"offsets": [
[
612,
628
]
],
"normalized": []
},
{
"id": "285",
"type": "protein_molecule",
"text": [
"IL-2R alpha"
],
"offsets": [
[
612,
623
]
],
"normalized": []
},
{
"id": "286",
"type": "other_name",
"text": [
"NF-kappa B activation"
],
"offsets": [
[
662,
683
]
],
"normalized": []
},
{
"id": "287",
"type": "protein_molecule",
"text": [
"NF-kappa B"
],
"offsets": [
[
662,
672
]
],
"normalized": []
},
{
"id": "288",
"type": "protein_molecule",
"text": [
"IL-2"
],
"offsets": [
[
716,
720
]
],
"normalized": []
},
{
"id": "289",
"type": "protein_molecule",
"text": [
"IL-2"
],
"offsets": [
[
780,
784
]
],
"normalized": []
},
{
"id": "290",
"type": "RNA_family_or_group",
"text": [
"IL-2R alpha transcripts"
],
"offsets": [
[
824,
847
]
],
"normalized": []
},
{
"id": "291",
"type": "protein_molecule",
"text": [
"IL-2R alpha"
],
"offsets": [
[
824,
835
]
],
"normalized": []
},
{
"id": "292",
"type": "other_name",
"text": [
"Transient transfection experiments"
],
"offsets": [
[
849,
883
]
],
"normalized": []
},
{
"id": "293",
"type": "DNA_domain_or_region",
"text": [
"promoter-proximal region"
],
"offsets": [
[
918,
942
]
],
"normalized": []
},
{
"id": "294",
"type": "DNA_domain_or_region",
"text": [
"IL-2R alpha gene"
],
"offsets": [
[
950,
966
]
],
"normalized": []
},
{
"id": "295",
"type": "protein_molecule",
"text": [
"IL-2R alpha"
],
"offsets": [
[
950,
961
]
],
"normalized": []
},
{
"id": "296",
"type": "protein_molecule",
"text": [
"IL-1"
],
"offsets": [
[
981,
985
]
],
"normalized": []
},
{
"id": "297",
"type": "DNA_domain_or_region",
"text": [
"NF-kappa B site"
],
"offsets": [
[
1022,
1037
]
],
"normalized": []
},
{
"id": "298",
"type": "protein_molecule",
"text": [
"NF-kappa B"
],
"offsets": [
[
1022,
1032
]
],
"normalized": []
},
{
"id": "299",
"type": "(AND DNA_family_or_group DNA_family_or_group)",
"text": [
"human and mouse gene"
],
"offsets": [
[
1055,
1075
]
],
"normalized": []
},
{
"id": "300",
"type": "",
"text": [
"human"
],
"offsets": [
[
1055,
1060
]
],
"normalized": []
},
{
"id": "301",
"type": "",
"text": [
"mouse"
],
"offsets": [
[
1065,
1070
]
],
"normalized": []
},
{
"id": "302",
"type": "",
"text": [
"gene"
],
"offsets": [
[
962,
966
]
],
"normalized": []
},
{
"id": "303",
"type": "other_name",
"text": [
"IL-2 responsiveness"
],
"offsets": [
[
1077,
1096
]
],
"normalized": []
},
{
"id": "304",
"type": "protein_molecule",
"text": [
"IL-2"
],
"offsets": [
[
1077,
1081
]
],
"normalized": []
},
{
"id": "305",
"type": "DNA_domain_or_region",
"text": [
"78-nucleotide segment"
],
"offsets": [
[
1130,
1151
]
],
"normalized": []
},
{
"id": "306",
"type": "DNA_domain_or_region",
"text": [
"major transcription start site"
],
"offsets": [
[
1182,
1212
]
],
"normalized": []
},
{
"id": "307",
"type": "DNA_domain_or_region",
"text": [
"IL-2-inducible enhancer"
],
"offsets": [
[
1243,
1266
]
],
"normalized": []
},
{
"id": "308",
"type": "other_name",
"text": [
"DNase I hypersensitive"
],
"offsets": [
[
1305,
1327
]
],
"normalized": []
},
{
"id": "309",
"type": "protein_molecule",
"text": [
"DNase I"
],
"offsets": [
[
1305,
1312
]
],
"normalized": []
},
{
"id": "310",
"type": "cell_type",
"text": [
"T cells"
],
"offsets": [
[
1338,
1345
]
],
"normalized": []
},
{
"id": "311",
"type": "other_name",
"text": [
"IL-2R alpha expression"
],
"offsets": [
[
1355,
1377
]
],
"normalized": []
},
{
"id": "312",
"type": "protein_molecule",
"text": [
"IL-2R alpha"
],
"offsets": [
[
1355,
1366
]
],
"normalized": []
},
{
"id": "313",
"type": "other_name",
"text": [
"IL-2 responsiveness"
],
"offsets": [
[
1396,
1415
]
],
"normalized": []
},
{
"id": "314",
"type": "protein_molecule",
"text": [
"IL-2"
],
"offsets": [
[
1396,
1400
]
],
"normalized": []
},
{
"id": "315",
"type": "DNA_domain_or_region",
"text": [
"elements"
],
"offsets": [
[
1440,
1448
]
],
"normalized": []
},
{
"id": "316",
"type": "DNA_domain_or_region",
"text": [
"enhancer"
],
"offsets": [
[
1460,
1468
]
],
"normalized": []
},
{
"id": "317",
"type": "protein_family_or_group",
"text": [
"STAT proteins"
],
"offsets": [
[
1515,
1528
]
],
"normalized": []
}
] | [] | [] | [] |
318 | 95338146 | [
{
"id": "319",
"type": "title",
"text": [
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0,
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"id": "320",
"type": "abstract",
"text": [
"This review focuses on the roles of transcription factors in hematopoietic lineage commitment. A brief introduction to lineage commitment and asymmetric cell division is followed by a discussion of several methods used to identify transcription factors important in specifying hematopoietic cell types. Next is presented a discussion of the use of embryonic stem cells in the analysis of hematopoietic gene expression and the use of targeted gene disruption to analyze the role of transcription factors in hematopoiesis. Finally, the status of our current knowledge concerning the roles of transcription factors in the commitment to erythroid, myeloid and lymphoid cell types is summarized."
],
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65,
755
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0,
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0,
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655,
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"id": "337",
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"erythroid, myeloid and lymphoid cell types"
],
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],
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{
"id": "338",
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"erythroid"
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{
"id": "339",
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{
"id": "341",
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"cell types"
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730,
740
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],
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}
] | [] | [] | [] |
342 | 95266275 | [
{
"id": "343",
"type": "title",
"text": [
"Epstein-Barr virus replicative gene transcription during de novo infection of human thymocytes: simultaneous early expression of BZLF-1 and its repressor RAZ."
],
"offsets": [
[
0,
158
]
]
},
{
"id": "344",
"type": "abstract",
"text": [
"Epstein-Barr virus (EBV) is known to infect B cells and epithelial cells. We and others have shown that EBV can also infect a subset of thymocytes. Infection of thymocytes was accompanied by the appearance of linear EBV genome within 8 hr of infection. Circularization of the EBV genome was not detected. This is in contrast to the infection in B cells where the genome can circularize within 24 hr of infection. The appearance of the BamHI ZLF-1 gene product, ZEBRA, by RT-PCR, was observed within 8 hr of infection. The appearance of a novel fusion transcript (RAZ), which comprised regions of the BZLF-1 locus and the adjacent BRLF-1 locus, was detected by RT-PCR. ZEBRA protein was also identified in infected thymocytes by immunoprecipitation. In addition, we demonstrated that the EBNA-1 gene in infected thymocytes was transcribed from the Fp promoter, rather than from the Cp/Wp promoter which is used in latently infected B cells. Transcripts encoding gp350/220, the major coat protein of EBV, were identified, but we did not find any evidence of transcription from the LMP-2A or EBER-1 loci in infected thymocytes. These observations suggest that de novo EBV infection of thymocytes differs from infection of B cells. The main difference is that with thymocytes, no evidence could be found that the virus ever circularizes. Rather, EBV remains in a linear configuration from which replicative genes are transcribed."
],
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[
159,
1584
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0,
49
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0,
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179,
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"B cells"
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203,
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"id": "355",
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215,
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"id": "356",
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263,
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],
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},
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"id": "357",
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295,
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"id": "358",
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320,
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"id": "359",
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368,
385
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375,
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435,
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504,
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630,
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789,
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819,
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887,
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"thymocytes"
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970,
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],
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{
"id": "380",
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1006,
1017
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},
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"id": "381",
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],
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[
1040,
1054
]
],
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},
{
"id": "382",
"type": "cell_type",
"text": [
"latently infected B cells"
],
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1072,
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],
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},
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"id": "383",
"type": "cell_type",
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"B cells"
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1090,
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],
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},
{
"id": "384",
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1120,
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],
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},
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"id": "385",
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"major coat protein"
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1135,
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],
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},
{
"id": "386",
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"EBV"
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1157,
1160
]
],
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},
{
"id": "387",
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1238,
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],
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{
"id": "388",
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1248,
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],
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},
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"id": "389",
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"thymocytes"
],
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1272,
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1324,
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"EBV"
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1324,
1327
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],
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},
{
"id": "392",
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"thymocytes"
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1341,
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],
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},
{
"id": "393",
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"B cells"
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1378,
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],
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},
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"id": "394",
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],
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1420,
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],
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"id": "395",
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"virus"
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},
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"id": "396",
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1501,
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},
{
"id": "397",
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{
"id": "398",
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"text": [
"replicative genes"
],
"offsets": [
[
1550,
1567
]
],
"normalized": []
}
] | [] | [] | [] |
399 | 95236292 | [
{
"id": "400",
"type": "title",
"text": [
"Identification and purification of human Stat proteins activated in response to interleukin-2."
],
"offsets": [
[
0,
94
]
]
},
{
"id": "401",
"type": "abstract",
"text": [
"A key cytokine induced during the immune response is IL-2. Following T cell activation, the genes encoding IL-2 and the various chains of its receptor are transcriptionally induced. In turn, secreted IL-2 serves to stimulate the proliferation and differentiation of T lymphocytes. Several recent studies have implicated Jak kinases in the signaling pathway induced by IL-2. Following this lead, we set out to identify transcription factors induced in response to IL-2. Human peripheral blood lymphocytes were observed to contain several IL-2-inducible DNA binding activities. Similar activities were also observed in a transformed human lymphocyte line, termed YT. We have purified these activities and found that the principal IL-2-inducible component bears significant relatedness to a prolactin-induced transcription factor first identified in sheep mammary gland tissue. We hypothesize that activation of this protein, designated hStat5, helps govern the biological effects of IL-2 during the immune response."
],
"offsets": [
[
95,
1108
]
]
}
] | [
{
"id": "402",
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"human Stat proteins"
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35,
54
]
],
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},
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"id": "403",
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80,
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101,
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],
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129,
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148,
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164,
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564,
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"id": "423",
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"id": "424",
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"id": "426",
"type": "other_name",
"text": [
"immune response"
],
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}
] | [] | [] | [] |
427 | 95197524 | [
{
"id": "428",
"type": "title",
"text": [
"E2F-1 and a cyclin-like DNA repair enzyme, uracil-DNA glycosylase, provide evidence for an autoregulatory mechanism for transcription."
],
"offsets": [
[
0,
134
]
]
},
{
"id": "429",
"type": "abstract",
"text": [
"The cell cycle-dependent transcription factor, E2F-1, regulates the cyclin-like species of the DNA repair enzyme uracil-DNA glycosylase (UDG) gene in human osteosarcoma (Saos-2) cells. We demonstrate, through the deletion of the human UDG promoter sequences, that expression of E2F-1 activates the UDG promoter through several E2F sites. The major putative downstream site for E2F, located in the first exon, serves as a target for E2F-1/DP1 complex binding in vitro. We also provide evidence for the functional relationship between the cyclin-like UDG gene product and E2F. High levels of UDG expression in a transient transfection assay result in the down-regulation of transcriptional activity through elements specific for E2F-mediated transcription. Overexpression of UDG in Saos 2 cells was observed to delay growth late in G1 phase and transiently arrest these cells from progressing into the S phase. This hypothetical model integrates one mechanism of DNA repair with the cell cycle control of gene transcription, likely through E2F. This implicates E2F as a multifunctional target for proteins and enzymes, possibly, responsive to DNA damage through the negative effect of UDG on E2F-mediated transcriptional activity."
],
"offsets": [
[
135,
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]
}
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"E2F-1"
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0,
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12,
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139,
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230,
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248,
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"UDG"
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],
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]
],
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305,
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413,
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"id": "450",
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512,
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{
"id": "452",
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532,
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705,
708
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"id": "460",
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},
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807,
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},
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"id": "462",
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"elements"
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840,
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862,
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},
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"id": "464",
"type": "protein_family_or_group",
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"E2F"
],
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[
862,
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]
],
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},
{
"id": "465",
"type": "other_name",
"text": [
"Overexpression"
],
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890,
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]
],
"normalized": []
},
{
"id": "466",
"type": "protein_molecule",
"text": [
"UDG"
],
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[
908,
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]
],
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},
{
"id": "467",
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"text": [
"Saos 2 cells"
],
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[
915,
927
]
],
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},
{
"id": "468",
"type": "other_name",
"text": [
"G1 phase"
],
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965,
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]
],
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},
{
"id": "469",
"type": "other_name",
"text": [
"S phase"
],
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[
1035,
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]
],
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},
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"id": "470",
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"DNA repair"
],
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},
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"id": "471",
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],
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},
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"id": "472",
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],
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],
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},
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1173,
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],
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},
{
"id": "474",
"type": "protein_family_or_group",
"text": [
"E2F"
],
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1194,
1197
]
],
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},
{
"id": "475",
"type": "other_name",
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],
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]
],
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},
{
"id": "476",
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]
],
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},
{
"id": "477",
"type": "other_name",
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],
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1325,
1362
]
],
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},
{
"id": "478",
"type": "protein_family_or_group",
"text": [
"E2F"
],
"offsets": [
[
1325,
1328
]
],
"normalized": []
}
] | [] | [] | [] |
479 | 95370702 | [
{
"id": "480",
"type": "title",
"text": [
"Cellular and molecular mechanisms of IFN-gamma production induced by IL-2 and IL-12 in a human NK cell line."
],
"offsets": [
[
0,
108
]
]
},
{
"id": "481",
"type": "abstract",
"text": [
"Interferon-gamma (IFN-gamma) is an important immunoregulatory protein produced predominantly by T cells and large granular lymphocytes (LGL) in response to different extracellular signals. In particular, two interleukins (ILs), IL-2 and IL-12, have been shown to be potent inducers of IFN-gamma gene expression in both T cells and LGL. Although it has been reported that there are some T cell lines that produce IFN-gamma in response to IL-2 and IL-12 stimulation, there has as yet been no report of a natural killer (NK) cell line that responds in a similar manner. In this report we present evidence that the cell line NK3.3 derived from human NK cells, responds to both IL-2 and IL-12, as measured by increases in IFN-gamma and granulocyte-macrophage colony-stimulating factor (GM-CSF) cytoplasmic mRNA and protein expression. In addition, when used together IL-2 and IL-12 synergized in the induction of IFN-gamma and GM-CSF and this synergy was attributed to an increased accumulation and stability of the IFN-gamma and GM-CSF mRNAs. To investigate the signaling pathways involved in the gene induction, five inhibitors, cyclosporin A (CsA), transforming growth factor-beta, cycloheximide, genistein, and staurosporine A, were used in analyzing the effects of IL-2 and IL-12 on NK3.3 cells. The results suggest that activation of protein kinase C, but not new protein synthesis, is required for IL-2 induction of IFN-gamma and GM-CSF cytoplasmic mRNA. In contrast, IL-12 induction of IFN-gamma cytoplasmic mRNA appears to only partially depend on activation of protein kinase C. Furthermore, both transforming growth factor-beta and genistein, a tyrosine kinase inhibitor, could suppress IL-2 and IL-12 signaling but CsA was generally inactive. It also was observed that suppression of cytokine gene expression by these agents was independent of the inhibition of proliferation. In addition, IL-2 but not IL-12 induced nuclear factors NF-kappa B and AP1, and regulation of the nuclear levels of these two DNA binding protein complexes is correlated with IFN-gamma and GM-CSF gene expression. These data indicate that IL-2 and IL-12 may have distinct signaling pathways leading to the induction of IFN-gamma and GM-CSF gene expression, and that the NK3.3 cell line may serve as a novel model for dissecting the biochemical and molecular events involved in these pathways."
],
"offsets": [
[
109,
2484
]
]
}
] | [
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"id": "482",
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0,
33
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],
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0,
8
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],
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205,
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275,
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394,
419
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394,
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428,
435
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},
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"id": "505",
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440,
443
]
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},
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495,
507
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521,
530
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},
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"id": "508",
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572
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546,
550
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555,
560
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720,
735
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791,
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890,
896
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},
{
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898,
937
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},
{
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909
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914
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},
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"id": "523",
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"text": [
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926
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],
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},
{
"id": "524",
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937
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1120,
1146
]
],
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1120,
1129
]
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1017,
1026
]
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1134,
1146
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1134,
1140
]
],
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},
{
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"cyclosporin A"
],
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[
1235,
1248
]
],
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},
{
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"CsA"
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1250,
1253
]
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1256,
1287
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{
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1289,
1302
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],
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{
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1304,
1313
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{
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1319,
1334
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1374,
1378
]
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1383,
1388
]
],
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},
{
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"NK3.3 cells"
],
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[
1392,
1403
]
],
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},
{
"id": "543",
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"protein kinase C"
],
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[
1444,
1460
]
],
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},
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],
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1470,
1491
]
],
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},
{
"id": "545",
"type": "protein_molecule",
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"IL-2"
],
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[
1509,
1513
]
],
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},
{
"id": "546",
"type": "(AND RNA_molecule RNA_molecule)",
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"IFN-gamma and GM-CSF cytoplasmic mRNA"
],
"offsets": [
[
1527,
1564
]
],
"normalized": []
},
{
"id": "547",
"type": "",
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"IFN-gamma"
],
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[
1527,
1536
]
],
"normalized": []
},
{
"id": "548",
"type": "",
"text": [
"GM-CSF"
],
"offsets": [
[
1541,
1547
]
],
"normalized": []
},
{
"id": "549",
"type": "",
"text": [
"cytoplasmic mRNA"
],
"offsets": [
[
1548,
1564
]
],
"normalized": []
},
{
"id": "550",
"type": "other_name",
"text": [
"IL-12 induction"
],
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[
1579,
1594
]
],
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},
{
"id": "551",
"type": "protein_molecule",
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"IL-12"
],
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1579,
1584
]
],
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},
{
"id": "552",
"type": "RNA_molecule",
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"IFN-gamma cytoplasmic mRNA"
],
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[
1598,
1624
]
],
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},
{
"id": "553",
"type": "protein_molecule",
"text": [
"IFN-gamma"
],
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[
1598,
1607
]
],
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},
{
"id": "554",
"type": "protein_molecule",
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],
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[
1675,
1691
]
],
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1711,
1742
]
],
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{
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"genistein"
],
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[
1747,
1756
]
],
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},
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1760,
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]
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1802,
1806
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{
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1811,
1816
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"CsA"
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[
1831,
1834
]
],
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},
{
"id": "561",
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"cytokine gene expression"
],
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1900,
1924
]
],
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},
{
"id": "562",
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"cytokine gene"
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1900,
1913
]
],
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},
{
"id": "563",
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],
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[
1964,
1991
]
],
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},
{
"id": "564",
"type": "protein_molecule",
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"IL-2"
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[
2006,
2010
]
],
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"IL-12"
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2019,
2024
]
],
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},
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"id": "566",
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],
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2033,
2048
]
],
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},
{
"id": "567",
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2049,
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2064,
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2091,
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]
],
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],
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2119,
2148
]
],
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},
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"type": "(AND other_name other_name)",
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"IFN-gamma and GM-CSF gene expression"
],
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2168,
2204
]
],
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},
{
"id": "572",
"type": "",
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"IFN-gamma"
],
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2168,
2177
]
],
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},
{
"id": "573",
"type": "",
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"GM-CSF"
],
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2182,
2188
]
],
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},
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"type": "",
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"gene expression"
],
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2189,
2204
]
],
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2264,
2282
]
],
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},
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"IFN-gamma"
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2311,
2320
]
],
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},
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"GM-CSF gene expression"
],
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],
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},
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"type": "protein_molecule",
"text": [
"GM-CSF"
],
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2325,
2331
]
],
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"NK3.3 cell line"
],
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[
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]
],
"normalized": []
},
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"id": "582",
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"text": [
"biochemical and molecular events"
],
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[
2424,
2456
]
],
"normalized": []
}
] | [] | [] | [] |
583 | 95349600 | [
{
"id": "584",
"type": "title",
"text": [
"A functional T-cell receptor signaling pathway is required for p95vav activity."
],
"offsets": [
[
0,
79
]
]
},
{
"id": "585",
"type": "abstract",
"text": [
"Stimulation of the T-cell antigen receptor (TCR) induces activation of multiple tyrosine kinases, resulting in phosphorylation of numerous intracellular substrates. One substrate is p95vav, which is expressed exclusively in hematopoietic and trophoblast cells. It contains a number of structural motifs, including Src homology 2, Src homology 3, and pleckstrin homology domains and a putative guanine nucleotide exchange domain. The role of p95vav in TCR-mediated signaling processes is unclear. Here, we show that overexpression of p95vav alone in Jurkat T cells leads to activation of the nuclear factors, including NFAT, involved in interleukin-2 expression. Furthermore, p95vav synergizes with TCR stimulation in inducing NFAT- and interleukin-2-dependent transcription. In contrast, NFAT activation by a G-protein-coupled receptor is not modulated by p95vav overexpression, suggesting that the effect is specific to the TCR signaling pathways. Although removal of the first 67 amino acids of p95vav activates its transforming potential in NIH 3T3 cells, this region appears to be required for its function in T cells. We further demonstrate that the p95vav-induced NFAT activation is not mimicked by Ras activation, though its function is dependent upon Ras and Raf. Furthermore, the activating function of p95vav is blocked by FK506, suggesting that its activity also depends on calcineurin. To further dissect p95vav involvement in TCR signaling, we analyzed various Jurkat mutants deficient in TCR signaling function or TCR expression and showed that an intact TCR signaling pathway is required for p95vav to function. However, overexpression of p95vav does not appear to influence TCR-induced protein tyrosine phosphorylation or increases in cytoplasmic free calcium. Taken together, our data suggest that p95vav plays an important role at an yet unidentified proximal position in the TCR signaling cascade."
],
"offsets": [
[
80,
1996
]
]
}
] | [
{
"id": "586",
"type": "other_name",
"text": [
"functional T-cell receptor signaling pathway"
],
"offsets": [
[
2,
46
]
],
"normalized": []
},
{
"id": "587",
"type": "protein_family_or_group",
"text": [
"T-cell receptor"
],
"offsets": [
[
13,
28
]
],
"normalized": []
},
{
"id": "588",
"type": "other_name",
"text": [
"p95vav activity"
],
"offsets": [
[
63,
78
]
],
"normalized": []
},
{
"id": "589",
"type": "protein_molecule",
"text": [
"p95vav"
],
"offsets": [
[
63,
69
]
],
"normalized": []
},
{
"id": "590",
"type": "protein_molecule",
"text": [
"T-cell antigen receptor"
],
"offsets": [
[
99,
122
]
],
"normalized": []
},
{
"id": "591",
"type": "protein_molecule",
"text": [
"TCR"
],
"offsets": [
[
124,
127
]
],
"normalized": []
},
{
"id": "592",
"type": "protein_molecule",
"text": [
"tyrosine kinases"
],
"offsets": [
[
160,
176
]
],
"normalized": []
},
{
"id": "593",
"type": "other_name",
"text": [
"phosphorylation"
],
"offsets": [
[
191,
206
]
],
"normalized": []
},
{
"id": "594",
"type": "other_organic_compound",
"text": [
"intracellular substrates"
],
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[
219,
243
]
],
"normalized": []
},
{
"id": "595",
"type": "protein_molecule",
"text": [
"p95vav"
],
"offsets": [
[
262,
268
]
],
"normalized": []
},
{
"id": "596",
"type": "(AND cell_type cell_type)",
"text": [
"hematopoietic and trophoblast cells"
],
"offsets": [
[
304,
339
]
],
"normalized": []
},
{
"id": "597",
"type": "",
"text": [
"hematopoietic"
],
"offsets": [
[
304,
317
]
],
"normalized": []
},
{
"id": "598",
"type": "",
"text": [
"trophoblast"
],
"offsets": [
[
322,
333
]
],
"normalized": []
},
{
"id": "599",
"type": "",
"text": [
"cells"
],
"offsets": [
[
334,
339
]
],
"normalized": []
},
{
"id": "600",
"type": "protein_substructure",
"text": [
"structural motifs"
],
"offsets": [
[
365,
382
]
],
"normalized": []
},
{
"id": "601",
"type": "protein_domain_or_region",
"text": [
"Src homology 2, Src homology 3, and pleckstrin homology domains"
],
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[
394,
457
]
],
"normalized": []
},
{
"id": "602",
"type": "protein_domain_or_region",
"text": [
"Src homology 2"
],
"offsets": [
[
394,
408
]
],
"normalized": []
},
{
"id": "603",
"type": "protein_domain_or_region",
"text": [
"Src homology 3"
],
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[
410,
424
]
],
"normalized": []
},
{
"id": "604",
"type": "protein_domain_or_region",
"text": [
"pleckstrin homology domains"
],
"offsets": [
[
430,
457
]
],
"normalized": []
},
{
"id": "605",
"type": "protein_domain_or_region",
"text": [
"putative guanine nucleotide exchange domain"
],
"offsets": [
[
464,
507
]
],
"normalized": []
},
{
"id": "606",
"type": "protein_molecule",
"text": [
"p95vav"
],
"offsets": [
[
521,
527
]
],
"normalized": []
},
{
"id": "607",
"type": "other_name",
"text": [
"TCR-mediated signaling processes"
],
"offsets": [
[
531,
563
]
],
"normalized": []
},
{
"id": "608",
"type": "protein_molecule",
"text": [
"TCR"
],
"offsets": [
[
531,
534
]
],
"normalized": []
},
{
"id": "609",
"type": "protein_molecule",
"text": [
"p95vav"
],
"offsets": [
[
613,
619
]
],
"normalized": []
},
{
"id": "610",
"type": "cell_type",
"text": [
"T cells"
],
"offsets": [
[
636,
643
]
],
"normalized": []
},
{
"id": "611",
"type": "protein_family_or_group",
"text": [
"nuclear factors"
],
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[
671,
686
]
],
"normalized": []
},
{
"id": "612",
"type": "protein_family_or_group",
"text": [
"NFAT"
],
"offsets": [
[
698,
702
]
],
"normalized": []
},
{
"id": "613",
"type": "other_name",
"text": [
"interleukin-2 expression"
],
"offsets": [
[
716,
740
]
],
"normalized": []
},
{
"id": "614",
"type": "protein_molecule",
"text": [
"interleukin-2"
],
"offsets": [
[
716,
729
]
],
"normalized": []
},
{
"id": "615",
"type": "protein_molecule",
"text": [
"p95vav"
],
"offsets": [
[
755,
761
]
],
"normalized": []
},
{
"id": "616",
"type": "other_name",
"text": [
"TCR stimulation"
],
"offsets": [
[
778,
793
]
],
"normalized": []
},
{
"id": "617",
"type": "protein_molecule",
"text": [
"TCR"
],
"offsets": [
[
778,
781
]
],
"normalized": []
},
{
"id": "618",
"type": "(AND other_name other_name)",
"text": [
"NFAT- and interleukin-2-dependent transcription"
],
"offsets": [
[
806,
853
]
],
"normalized": []
},
{
"id": "619",
"type": "",
"text": [
"NFAT-"
],
"offsets": [
[
806,
811
]
],
"normalized": []
},
{
"id": "620",
"type": "",
"text": [
"interleukin-2-"
],
"offsets": [
[
816,
830
]
],
"normalized": []
},
{
"id": "621",
"type": "",
"text": [
"dependent transcription"
],
"offsets": [
[
830,
853
]
],
"normalized": []
},
{
"id": "622",
"type": "other_name",
"text": [
"NFAT activation"
],
"offsets": [
[
868,
883
]
],
"normalized": []
},
{
"id": "623",
"type": "protein_family_or_group",
"text": [
"NFAT"
],
"offsets": [
[
868,
872
]
],
"normalized": []
},
{
"id": "624",
"type": "protein_family_or_group",
"text": [
"G-protein-coupled receptor"
],
"offsets": [
[
889,
915
]
],
"normalized": []
},
{
"id": "625",
"type": "other_name",
"text": [
"p95vav overexpression"
],
"offsets": [
[
936,
957
]
],
"normalized": []
},
{
"id": "626",
"type": "protein_molecule",
"text": [
"p95vav"
],
"offsets": [
[
936,
942
]
],
"normalized": []
},
{
"id": "627",
"type": "other_name",
"text": [
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],
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1005,
1027
]
],
"normalized": []
},
{
"id": "628",
"type": "protein_molecule",
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"TCR"
],
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[
1005,
1008
]
],
"normalized": []
},
{
"id": "629",
"type": "other_name",
"text": [
"signaling pathways"
],
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[
1009,
1027
]
],
"normalized": []
},
{
"id": "630",
"type": "protein_domain_or_region",
"text": [
"first 67 amino acids"
],
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[
1053,
1073
]
],
"normalized": []
},
{
"id": "631",
"type": "protein_molecule",
"text": [
"p95vav"
],
"offsets": [
[
1077,
1083
]
],
"normalized": []
},
{
"id": "632",
"type": "other_name",
"text": [
"transforming potential"
],
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[
1098,
1120
]
],
"normalized": []
},
{
"id": "633",
"type": "cell_line",
"text": [
"NIH 3T3 cells"
],
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[
1124,
1137
]
],
"normalized": []
},
{
"id": "634",
"type": "cell_type",
"text": [
"T cells"
],
"offsets": [
[
1194,
1201
]
],
"normalized": []
},
{
"id": "635",
"type": "other_name",
"text": [
"p95vav-induced NFAT activation"
],
"offsets": [
[
1235,
1265
]
],
"normalized": []
},
{
"id": "636",
"type": "protein_molecule",
"text": [
"p95vav"
],
"offsets": [
[
1235,
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] | [] | [] | [] |
669 | 95329717 | [
{
"id": "670",
"type": "title",
"text": [
"Positive and negative regulation of granulocyte-macrophage colony-stimulating factor promoter activity by AML1-related transcription factor, PEBP2."
],
"offsets": [
[
0,
147
]
]
},
{
"id": "671",
"type": "abstract",
"text": [
"The granulocyte-macrophage colony-stimulating factor (GM-CSF) gene promoter contains a consensus sequence for the polyomavirus enhancer binding-protein 2 (PEBP2) transcription factor, which consists of alpha and beta subunits. There are at least two genes, alpha A and alpha B, encoding the alpha subunit. alpha B is the mouse homologue of human AML1 gene detected at the breakpoints of t(8;21) and t(3;21) myeloid leukemias. We examined alpha A1 (an alpha A-gene product) and alpha B1 and alpha B2 (two alpha B-encoded isomers) for their effects on the GM-CSF promoter. PEBP2 alpha A1, alpha B1, and alpha B2 proteins bound the PEBP2 site within the mouse GM-CSF promoter. PEBP2 alpha A1 and alpha B1 enhanced the expression of the GM-CSF promoter-driven reporter plasmid in unstimulated and 12-O-tetradecanoylphorbol 13-acetate/phytohemagglutinin-stimulated human Jurkat T cells. In contrast, the promoter activity was suppressed by alpha B2. Coexpression of alpha B1 and alpha B2 showed that the promoter activity could be determined by the alpha B1/alpha B2 ratio. Jurkat cell extract contained PEBP2 site-binding protein(s) that cross-reacted with antimouse alpha A1 antibodies. Northern blot analysis indicated the expression of human PEBP2 alpha A, alpha B (AML1), and beta genes in Jurkat cells. Although further studies are required to determine the precise role of PEBP2 in the GM-CSF promoter activity, the present findings suggested the importance of the relative ratio of different PEBP2 isoforms in regulating the levels of the promoter activity."
],
"offsets": [
[
148,
1708
]
]
}
] | [
{
"id": "672",
"type": "(AND other_name other_name)",
"text": [
"Positive and negative regulation"
],
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[
0,
32
]
],
"normalized": []
},
{
"id": "673",
"type": "",
"text": [
"Positive"
],
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[
0,
8
]
],
"normalized": []
},
{
"id": "674",
"type": "",
"text": [
"negative"
],
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[
13,
21
]
],
"normalized": []
},
{
"id": "675",
"type": "",
"text": [
"regulation"
],
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[
22,
32
]
],
"normalized": []
},
{
"id": "676",
"type": "other_name",
"text": [
"granulocyte-macrophage colony-stimulating factor promoter activity"
],
"offsets": [
[
36,
102
]
],
"normalized": []
},
{
"id": "677",
"type": "protein_molecule",
"text": [
"granulocyte-macrophage colony-stimulating factor"
],
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[
36,
84
]
],
"normalized": []
},
{
"id": "678",
"type": "protein_molecule",
"text": [
"AML1-related transcription factor"
],
"offsets": [
[
106,
139
]
],
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},
{
"id": "679",
"type": "protein_molecule",
"text": [
"PEBP2"
],
"offsets": [
[
141,
146
]
],
"normalized": []
},
{
"id": "680",
"type": "DNA_domain_or_region",
"text": [
"granulocyte-macrophage colony-stimulating factor (GM-CSF) gene promoter"
],
"offsets": [
[
152,
223
]
],
"normalized": []
},
{
"id": "681",
"type": "protein_molecule",
"text": [
"granulocyte-macrophage colony-stimulating factor"
],
"offsets": [
[
152,
200
]
],
"normalized": []
},
{
"id": "682",
"type": "protein_molecule",
"text": [
"GM-CSF"
],
"offsets": [
[
202,
208
]
],
"normalized": []
},
{
"id": "683",
"type": "protein_molecule",
"text": [
"polyomavirus enhancer binding-protein 2 (PEBP2) transcription factor"
],
"offsets": [
[
262,
330
]
],
"normalized": []
},
{
"id": "684",
"type": "protein_molecule",
"text": [
"polyomavirus enhancer binding-protein 2"
],
"offsets": [
[
262,
301
]
],
"normalized": []
},
{
"id": "685",
"type": "protein_molecule",
"text": [
"PEBP2"
],
"offsets": [
[
303,
308
]
],
"normalized": []
},
{
"id": "686",
"type": "(AND protein_subunit protein_subunit)",
"text": [
"alpha and beta subunits"
],
"offsets": [
[
350,
373
]
],
"normalized": []
},
{
"id": "687",
"type": "",
"text": [
"alpha"
],
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[
350,
355
]
],
"normalized": []
},
{
"id": "688",
"type": "",
"text": [
"beta"
],
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[
360,
364
]
],
"normalized": []
},
{
"id": "689",
"type": "",
"text": [
"subunits"
],
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[
365,
373
]
],
"normalized": []
},
{
"id": "690",
"type": "DNA_domain_or_region",
"text": [
"alpha A"
],
"offsets": [
[
405,
412
]
],
"normalized": []
},
{
"id": "691",
"type": "DNA_domain_or_region",
"text": [
"alpha B"
],
"offsets": [
[
417,
424
]
],
"normalized": []
},
{
"id": "692",
"type": "protein_subunit",
"text": [
"alpha subunit"
],
"offsets": [
[
439,
452
]
],
"normalized": []
},
{
"id": "693",
"type": "DNA_domain_or_region",
"text": [
"alpha B"
],
"offsets": [
[
454,
461
]
],
"normalized": []
},
{
"id": "694",
"type": "DNA_family_or_group",
"text": [
"mouse homologue"
],
"offsets": [
[
469,
484
]
],
"normalized": []
},
{
"id": "695",
"type": "DNA_domain_or_region",
"text": [
"human AML1 gene"
],
"offsets": [
[
488,
503
]
],
"normalized": []
},
{
"id": "696",
"type": "(AND other_artificial_source other_artificial_source)",
"text": [
"t(8;21) and t(3;21) myeloid leukemias"
],
"offsets": [
[
535,
572
]
],
"normalized": []
},
{
"id": "697",
"type": "",
"text": [
"t(8;21)"
],
"offsets": [
[
535,
542
]
],
"normalized": []
},
{
"id": "698",
"type": "",
"text": [
"t(3;21)"
],
"offsets": [
[
547,
554
]
],
"normalized": []
},
{
"id": "699",
"type": "",
"text": [
"myeloid leukemias"
],
"offsets": [
[
555,
572
]
],
"normalized": []
},
{
"id": "700",
"type": "protein_subunit",
"text": [
"alpha A1"
],
"offsets": [
[
586,
594
]
],
"normalized": []
},
{
"id": "701",
"type": "protein_family_or_group",
"text": [
"alpha A-gene product"
],
"offsets": [
[
599,
619
]
],
"normalized": []
},
{
"id": "702",
"type": "DNA_domain_or_region",
"text": [
"alpha A"
],
"offsets": [
[
586,
593
]
],
"normalized": []
},
{
"id": "703",
"type": "protein_subunit",
"text": [
"alpha B1"
],
"offsets": [
[
625,
633
]
],
"normalized": []
},
{
"id": "704",
"type": "protein_subunit",
"text": [
"alpha B2"
],
"offsets": [
[
638,
646
]
],
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},
{
"id": "705",
"type": "protein_family_or_group",
"text": [
"alpha B-encoded isomers"
],
"offsets": [
[
652,
675
]
],
"normalized": []
},
{
"id": "706",
"type": "DNA_domain_or_region",
"text": [
"alpha B"
],
"offsets": [
[
625,
632
]
],
"normalized": []
},
{
"id": "707",
"type": "protein_subunit",
"text": [
"alpha B"
],
"offsets": [
[
625,
632
]
],
"normalized": []
},
{
"id": "708",
"type": "DNA_domain_or_region",
"text": [
"GM-CSF promoter"
],
"offsets": [
[
702,
717
]
],
"normalized": []
},
{
"id": "709",
"type": "protein_molecule",
"text": [
"PEBP2 alpha A1"
],
"offsets": [
[
719,
733
]
],
"normalized": []
},
{
"id": "710",
"type": "protein_molecule",
"text": [
"PEBP2"
],
"offsets": [
[
719,
724
]
],
"normalized": []
},
{
"id": "711",
"type": "protein_subunit",
"text": [
"alpha A1"
],
"offsets": [
[
725,
733
]
],
"normalized": []
},
{
"id": "712",
"type": "protein_subunit",
"text": [
"alpha B1"
],
"offsets": [
[
735,
743
]
],
"normalized": []
},
{
"id": "713",
"type": "protein_family_or_group",
"text": [
"alpha B2 proteins"
],
"offsets": [
[
749,
766
]
],
"normalized": []
},
{
"id": "714",
"type": "DNA_domain_or_region",
"text": [
"PEBP2 site"
],
"offsets": [
[
777,
787
]
],
"normalized": []
},
{
"id": "715",
"type": "protein_molecule",
"text": [
"PEBP2"
],
"offsets": [
[
777,
782
]
],
"normalized": []
},
{
"id": "716",
"type": "DNA_domain_or_region",
"text": [
"mouse GM-CSF promoter"
],
"offsets": [
[
799,
820
]
],
"normalized": []
},
{
"id": "717",
"type": "protein_molecule",
"text": [
"GM-CSF"
],
"offsets": [
[
805,
811
]
],
"normalized": []
},
{
"id": "718",
"type": "protein_molecule",
"text": [
"PEBP2 alpha A1"
],
"offsets": [
[
822,
836
]
],
"normalized": []
},
{
"id": "719",
"type": "protein_molecule",
"text": [
"PEBP2"
],
"offsets": [
[
822,
827
]
],
"normalized": []
},
{
"id": "720",
"type": "protein_subunit",
"text": [
"alpha A1"
],
"offsets": [
[
828,
836
]
],
"normalized": []
},
{
"id": "721",
"type": "protein_subunit",
"text": [
"alpha B1"
],
"offsets": [
[
841,
849
]
],
"normalized": []
},
{
"id": "722",
"type": "DNA_molecule",
"text": [
"GM-CSF promoter-driven reporter plasmid"
],
"offsets": [
[
881,
920
]
],
"normalized": []
},
{
"id": "723",
"type": "protein_molecule",
"text": [
"GM-CSF"
],
"offsets": [
[
881,
887
]
],
"normalized": []
},
{
"id": "724",
"type": "(AND cell_line cell_line)",
"text": [
"unstimulated and 12-O-tetradecanoylphorbol 13-acetate/phytohemagglutinin-stimulated human Jurkat T cells"
],
"offsets": [
[
924,
1028
]
],
"normalized": []
},
{
"id": "725",
"type": "",
"text": [
"unstimulated"
],
"offsets": [
[
924,
936
]
],
"normalized": []
},
{
"id": "726",
"type": "",
"text": [
"12-O-tetradecanoylphorbol 13-acetate/phytohemagglutinin-stimulated"
],
"offsets": [
[
941,
1007
]
],
"normalized": []
},
{
"id": "727",
"type": "",
"text": [
"human Jurkat T cells"
],
"offsets": [
[
1008,
1028
]
],
"normalized": []
},
{
"id": "728",
"type": "other_name",
"text": [
"promoter activity"
],
"offsets": [
[
1047,
1064
]
],
"normalized": []
},
{
"id": "729",
"type": "protein_subunit",
"text": [
"alpha B2"
],
"offsets": [
[
1083,
1091
]
],
"normalized": []
},
{
"id": "730",
"type": "protein_subunit",
"text": [
"alpha B1"
],
"offsets": [
[
1109,
1117
]
],
"normalized": []
},
{
"id": "731",
"type": "protein_subunit",
"text": [
"alpha B2"
],
"offsets": [
[
1122,
1130
]
],
"normalized": []
},
{
"id": "732",
"type": "other_name",
"text": [
"promoter activity"
],
"offsets": [
[
1147,
1164
]
],
"normalized": []
},
{
"id": "733",
"type": "other_name",
"text": [
"alpha B1/alpha B2 ratio"
],
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[
1192,
1215
]
],
"normalized": []
},
{
"id": "734",
"type": "protein_subunit",
"text": [
"alpha B1"
],
"offsets": [
[
1192,
1200
]
],
"normalized": []
},
{
"id": "735",
"type": "protein_subunit",
"text": [
"/alpha B2"
],
"offsets": [
[
1200,
1209
]
],
"normalized": []
},
{
"id": "736",
"type": "cell_component",
"text": [
"Jurkat cell extract"
],
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[
1217,
1236
]
],
"normalized": []
},
{
"id": "737",
"type": "protein_family_or_group",
"text": [
"PEBP2 site-binding protein"
],
"offsets": [
[
1247,
1273
]
],
"normalized": []
},
{
"id": "738",
"type": "protein_molecule",
"text": [
"PEBP2"
],
"offsets": [
[
1247,
1252
]
],
"normalized": []
},
{
"id": "739",
"type": "protein_family_or_group",
"text": [
"antimouse alpha A1 antibodies"
],
"offsets": [
[
1301,
1330
]
],
"normalized": []
},
{
"id": "740",
"type": "protein_subunit",
"text": [
"alpha A1"
],
"offsets": [
[
1311,
1319
]
],
"normalized": []
},
{
"id": "741",
"type": "other_name",
"text": [
"Northern blot analysis"
],
"offsets": [
[
1332,
1354
]
],
"normalized": []
},
{
"id": "742",
"type": "protein_molecule",
"text": [
"PEBP2 alpha A"
],
"offsets": [
[
1389,
1402
]
],
"normalized": []
},
{
"id": "743",
"type": "protein_molecule",
"text": [
"PEBP2"
],
"offsets": [
[
1389,
1394
]
],
"normalized": []
},
{
"id": "744",
"type": "DNA_domain_or_region",
"text": [
"alpha B"
],
"offsets": [
[
1404,
1411
]
],
"normalized": []
},
{
"id": "745",
"type": "protein_subunit",
"text": [
"alpha B"
],
"offsets": [
[
1404,
1411
]
],
"normalized": []
},
{
"id": "746",
"type": "DNA_domain_or_region",
"text": [
"AML1"
],
"offsets": [
[
1413,
1417
]
],
"normalized": []
},
{
"id": "747",
"type": "DNA_domain_or_region",
"text": [
"beta genes"
],
"offsets": [
[
1424,
1434
]
],
"normalized": []
},
{
"id": "748",
"type": "cell_line",
"text": [
"Jurkat cells"
],
"offsets": [
[
1438,
1450
]
],
"normalized": []
},
{
"id": "749",
"type": "protein_molecule",
"text": [
"PEBP2"
],
"offsets": [
[
1523,
1528
]
],
"normalized": []
},
{
"id": "750",
"type": "other_name",
"text": [
"GM-CSF promoter activity"
],
"offsets": [
[
1536,
1560
]
],
"normalized": []
},
{
"id": "751",
"type": "protein_molecule",
"text": [
"GM-CSF"
],
"offsets": [
[
1536,
1542
]
],
"normalized": []
},
{
"id": "752",
"type": "other_name",
"text": [
"promoter activity"
],
"offsets": [
[
1543,
1560
]
],
"normalized": []
},
{
"id": "753",
"type": "protein_family_or_group",
"text": [
"PEBP2 isoforms"
],
"offsets": [
[
1643,
1657
]
],
"normalized": []
},
{
"id": "754",
"type": "protein_molecule",
"text": [
"PEBP2"
],
"offsets": [
[
1643,
1648
]
],
"normalized": []
},
{
"id": "755",
"type": "other_name",
"text": [
"promoter activity"
],
"offsets": [
[
1690,
1707
]
],
"normalized": []
}
] | [] | [] | [] |
756 | 96075792 | [
{
"id": "757",
"type": "title",
"text": [
"IFN-gamma priming of monocytes enhances LPS-induced TNF production by augmenting both transcription and MRNA stability."
],
"offsets": [
[
0,
119
]
]
},
{
"id": "758",
"type": "abstract",
"text": [
"The induction of cytokine expression in monocytes/macrophages by bacterial endotoxin or lipopolysaccharide is a critical, highly regulated host defence response. The augmentation of LPS responses by interferon gamma (IFN-gamma), referred to as priming, is well established. However, the mechanism(s) by which priming occurs is poorly defined. Using tumour necrosis factor (TNF) induction as a model, experiments were designed to analyse in detail the priming effect on the LPS response in human monocytes. Priming by IFN-gamma was primarily manifested at the level of TNF mRNA accumulation. IFN-gamma pre-treatment affected the magnitude rather than the sensitivity of the LPS response. Priming occurred after several hours of treatment, and the primed state was induced by either IFN-gamma or GM-CSF, but not M-CSF. Primed monocytes transcribed TNF mRNA at a higher rate than freshly isolated monocytes upon activation with LPS. The increased transcriptional rate correlated with a marked increase in nuclear factor-kappa B activity in these cells as determined by electrophoretic mobility shift assay using a consensus NF-kappa B oligonucleotide. An additional significant finding was than TNF mRNA induced in primed cells was much more stable than in unprimed cells (T1/2 increased 6-8-fold). Consistent with the increased mRNA stability, the duration of mRNA accumulation was longer following LPS stimulation in primed monocytes, in addition to being of greater magnitude. Finally, primed and unprimed cells possessed a differential sensitivity to the kinase inhibitor H-89. H-89 substantially suppressed LPS-induced TNF mRNA accumulation in unprimed cells, but had no effect on primed monocytes following LPS stimulation. (ABSTRACT TRUNCATED AT 250 WORDS)"
],
"offsets": [
[
120,
1880
]
]
}
] | [
{
"id": "759",
"type": "protein_molecule",
"text": [
"IFN-gamma"
],
"offsets": [
[
0,
9
]
],
"normalized": []
},
{
"id": "760",
"type": "cell_type",
"text": [
"monocytes"
],
"offsets": [
[
21,
30
]
],
"normalized": []
},
{
"id": "761",
"type": "other_name",
"text": [
"LPS-induced TNF production"
],
"offsets": [
[
40,
66
]
],
"normalized": []
},
{
"id": "762",
"type": "lipid",
"text": [
"LPS"
],
"offsets": [
[
40,
43
]
],
"normalized": []
},
{
"id": "763",
"type": "protein_family_or_group",
"text": [
"TNF"
],
"offsets": [
[
52,
55
]
],
"normalized": []
},
{
"id": "764",
"type": "other_name",
"text": [
"transcription"
],
"offsets": [
[
86,
99
]
],
"normalized": []
},
{
"id": "765",
"type": "other_name",
"text": [
"MRNA stability"
],
"offsets": [
[
104,
118
]
],
"normalized": []
},
{
"id": "766",
"type": "other_name",
"text": [
"cytokine expression"
],
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[
137,
156
]
],
"normalized": []
},
{
"id": "767",
"type": "protein_family_or_group",
"text": [
"cytokine"
],
"offsets": [
[
137,
145
]
],
"normalized": []
},
{
"id": "768",
"type": "cell_type",
"text": [
"monocytes"
],
"offsets": [
[
160,
169
]
],
"normalized": []
},
{
"id": "769",
"type": "cell_type",
"text": [
"macrophages"
],
"offsets": [
[
170,
181
]
],
"normalized": []
},
{
"id": "770",
"type": "protein_family_or_group",
"text": [
"bacterial endotoxin"
],
"offsets": [
[
185,
204
]
],
"normalized": []
},
{
"id": "771",
"type": "lipid",
"text": [
"lipopolysaccharide"
],
"offsets": [
[
208,
226
]
],
"normalized": []
},
{
"id": "772",
"type": "other_name",
"text": [
"host defence response"
],
"offsets": [
[
259,
280
]
],
"normalized": []
},
{
"id": "773",
"type": "lipid",
"text": [
"LPS"
],
"offsets": [
[
302,
305
]
],
"normalized": []
},
{
"id": "774",
"type": "protein_molecule",
"text": [
"interferon gamma"
],
"offsets": [
[
319,
335
]
],
"normalized": []
},
{
"id": "775",
"type": "protein_molecule",
"text": [
"IFN-gamma"
],
"offsets": [
[
337,
346
]
],
"normalized": []
},
{
"id": "776",
"type": "other_name",
"text": [
"tumour necrosis factor (TNF) induction"
],
"offsets": [
[
469,
507
]
],
"normalized": []
},
{
"id": "777",
"type": "protein_family_or_group",
"text": [
"tumour necrosis factor"
],
"offsets": [
[
469,
491
]
],
"normalized": []
},
{
"id": "778",
"type": "protein_family_or_group",
"text": [
"TNF"
],
"offsets": [
[
493,
496
]
],
"normalized": []
},
{
"id": "779",
"type": "other_name",
"text": [
"priming effect"
],
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[
571,
585
]
],
"normalized": []
},
{
"id": "780",
"type": "lipid",
"text": [
"LPS"
],
"offsets": [
[
593,
596
]
],
"normalized": []
},
{
"id": "781",
"type": "cell_type",
"text": [
"human monocytes"
],
"offsets": [
[
609,
624
]
],
"normalized": []
},
{
"id": "782",
"type": "cell_type",
"text": [
"monocytes"
],
"offsets": [
[
615,
624
]
],
"normalized": []
},
{
"id": "783",
"type": "protein_molecule",
"text": [
"IFN-gamma"
],
"offsets": [
[
637,
646
]
],
"normalized": []
},
{
"id": "784",
"type": "other_name",
"text": [
"TNF mRNA accumulation"
],
"offsets": [
[
688,
709
]
],
"normalized": []
},
{
"id": "785",
"type": "RNA_family_or_group",
"text": [
"TNF mRNA"
],
"offsets": [
[
688,
696
]
],
"normalized": []
},
{
"id": "786",
"type": "protein_family_or_group",
"text": [
"TNF"
],
"offsets": [
[
688,
691
]
],
"normalized": []
},
{
"id": "787",
"type": "other_name",
"text": [
"IFN-gamma pre-treatment"
],
"offsets": [
[
711,
734
]
],
"normalized": []
},
{
"id": "788",
"type": "protein_molecule",
"text": [
"IFN-gamma"
],
"offsets": [
[
711,
720
]
],
"normalized": []
},
{
"id": "789",
"type": "other_name",
"text": [
"LPS response"
],
"offsets": [
[
793,
805
]
],
"normalized": []
},
{
"id": "790",
"type": "lipid",
"text": [
"LPS"
],
"offsets": [
[
793,
796
]
],
"normalized": []
},
{
"id": "791",
"type": "other_name",
"text": [
"treatment"
],
"offsets": [
[
847,
856
]
],
"normalized": []
},
{
"id": "792",
"type": "other_name",
"text": [
"primed state"
],
"offsets": [
[
866,
878
]
],
"normalized": []
},
{
"id": "793",
"type": "protein_molecule",
"text": [
"IFN-gamma"
],
"offsets": [
[
901,
910
]
],
"normalized": []
},
{
"id": "794",
"type": "protein_molecule",
"text": [
"GM-CSF"
],
"offsets": [
[
914,
920
]
],
"normalized": []
},
{
"id": "795",
"type": "protein_molecule",
"text": [
"M-CSF"
],
"offsets": [
[
915,
920
]
],
"normalized": []
},
{
"id": "796",
"type": "cell_type",
"text": [
"monocytes"
],
"offsets": [
[
944,
953
]
],
"normalized": []
},
{
"id": "797",
"type": "RNA_family_or_group",
"text": [
"TNF mRNA"
],
"offsets": [
[
966,
974
]
],
"normalized": []
},
{
"id": "798",
"type": "protein_family_or_group",
"text": [
"TNF"
],
"offsets": [
[
966,
969
]
],
"normalized": []
},
{
"id": "799",
"type": "cell_type",
"text": [
"monocytes"
],
"offsets": [
[
1014,
1023
]
],
"normalized": []
},
{
"id": "800",
"type": "lipid",
"text": [
"LPS"
],
"offsets": [
[
1045,
1048
]
],
"normalized": []
},
{
"id": "801",
"type": "other_name",
"text": [
"transcriptional rate"
],
"offsets": [
[
1064,
1084
]
],
"normalized": []
},
{
"id": "802",
"type": "other_name",
"text": [
"nuclear factor-kappa B activity"
],
"offsets": [
[
1122,
1153
]
],
"normalized": []
},
{
"id": "803",
"type": "protein_molecule",
"text": [
"nuclear factor-kappa B"
],
"offsets": [
[
1122,
1144
]
],
"normalized": []
},
{
"id": "804",
"type": "other_name",
"text": [
"electrophoretic mobility shift assay"
],
"offsets": [
[
1186,
1222
]
],
"normalized": []
},
{
"id": "805",
"type": "DNA_molecule",
"text": [
"consensus NF-kappa B oligonucleotide"
],
"offsets": [
[
1231,
1267
]
],
"normalized": []
},
{
"id": "806",
"type": "protein_molecule",
"text": [
"NF-kappa B"
],
"offsets": [
[
1241,
1251
]
],
"normalized": []
},
{
"id": "807",
"type": "RNA_family_or_group",
"text": [
"TNF mRNA"
],
"offsets": [
[
1312,
1320
]
],
"normalized": []
},
{
"id": "808",
"type": "protein_family_or_group",
"text": [
"TNF"
],
"offsets": [
[
1312,
1315
]
],
"normalized": []
},
{
"id": "809",
"type": "cell_line",
"text": [
"primed cells"
],
"offsets": [
[
1332,
1344
]
],
"normalized": []
},
{
"id": "810",
"type": "cell_line",
"text": [
"unprimed cells"
],
"offsets": [
[
1374,
1388
]
],
"normalized": []
},
{
"id": "811",
"type": "other_name",
"text": [
"mRNA stability"
],
"offsets": [
[
1446,
1460
]
],
"normalized": []
},
{
"id": "812",
"type": "RNA_family_or_group",
"text": [
"mRNA"
],
"offsets": [
[
1446,
1450
]
],
"normalized": []
},
{
"id": "813",
"type": "other_name",
"text": [
"mRNA accumulation"
],
"offsets": [
[
1478,
1495
]
],
"normalized": []
},
{
"id": "814",
"type": "RNA_family_or_group",
"text": [
"mRNA"
],
"offsets": [
[
1478,
1482
]
],
"normalized": []
},
{
"id": "815",
"type": "lipid",
"text": [
"LPS"
],
"offsets": [
[
1517,
1520
]
],
"normalized": []
},
{
"id": "816",
"type": "cell_type",
"text": [
"monocytes"
],
"offsets": [
[
1543,
1552
]
],
"normalized": []
},
{
"id": "817",
"type": "other_organic_compound",
"text": [
"kinase inhibitor H-89"
],
"offsets": [
[
1676,
1697
]
],
"normalized": []
},
{
"id": "818",
"type": "other_organic_compound",
"text": [
"H-89"
],
"offsets": [
[
1699,
1703
]
],
"normalized": []
},
{
"id": "819",
"type": "other_name",
"text": [
"LPS-induced TNF mRNA accumulation"
],
"offsets": [
[
1729,
1762
]
],
"normalized": []
},
{
"id": "820",
"type": "lipid",
"text": [
"LPS"
],
"offsets": [
[
1729,
1732
]
],
"normalized": []
},
{
"id": "821",
"type": "RNA_family_or_group",
"text": [
"TNF mRNA"
],
"offsets": [
[
1741,
1749
]
],
"normalized": []
},
{
"id": "822",
"type": "protein_family_or_group",
"text": [
"TNF"
],
"offsets": [
[
1741,
1744
]
],
"normalized": []
},
{
"id": "823",
"type": "cell_line",
"text": [
"unprimed cells"
],
"offsets": [
[
1766,
1780
]
],
"normalized": []
},
{
"id": "824",
"type": "cell_line",
"text": [
"primed monocytes"
],
"offsets": [
[
1803,
1819
]
],
"normalized": []
},
{
"id": "825",
"type": "cell_type",
"text": [
"monocytes"
],
"offsets": [
[
1810,
1819
]
],
"normalized": []
},
{
"id": "826",
"type": "other_name",
"text": [
"LPS stimulation"
],
"offsets": [
[
1830,
1845
]
],
"normalized": []
},
{
"id": "827",
"type": "lipid",
"text": [
"LPS"
],
"offsets": [
[
1830,
1833
]
],
"normalized": []
}
] | [] | [] | [] |
828 | 95280917 | [
{
"id": "829",
"type": "title",
"text": [
"A Myc-associated zinc finger protein binding site is one of four important functional regions in the CD4 promoter."
],
"offsets": [
[
0,
114
]
]
},
{
"id": "830",
"type": "abstract",
"text": [
"The CD4 promoter plays an important role in the developmental control of CD4 transcription. In this report, we show that the minimal CD4 promoter has four factor binding sites, each of which is required for full function. Using biochemical and mutagenesis analyses, we determined that multiple nuclear factors bind to these independent sites. We determined that an initiator-like sequence present at the cap site and an Ets consensus sequence are required for full promoter function. We also demonstrate that the Myc-associated zinc finger protein (MAZ) appears to be the predominant factor binding to one of these sites. This last site closely resembles the ME1a1 G3AG4AG3 motif previously shown to be a critical element in the P2 promoter of the c-myc gene. We therefore believe that the MAZ transcription factor is also likely to play an important role in the control of developmental expression of the CD4 gene."
],
"offsets": [
[
115,
1030
]
]
}
] | [
{
"id": "831",
"type": "DNA_domain_or_region",
"text": [
"Myc-associated zinc finger protein binding site"
],
"offsets": [
[
2,
49
]
],
"normalized": []
},
{
"id": "832",
"type": "protein_family_or_group",
"text": [
"Myc-associated zinc finger protein"
],
"offsets": [
[
2,
36
]
],
"normalized": []
},
{
"id": "833",
"type": "DNA_domain_or_region",
"text": [
"functional regions"
],
"offsets": [
[
75,
93
]
],
"normalized": []
},
{
"id": "834",
"type": "DNA_domain_or_region",
"text": [
"CD4 promoter"
],
"offsets": [
[
101,
113
]
],
"normalized": []
},
{
"id": "835",
"type": "protein_molecule",
"text": [
"CD4"
],
"offsets": [
[
101,
104
]
],
"normalized": []
},
{
"id": "836",
"type": "DNA_domain_or_region",
"text": [
"CD4 promoter"
],
"offsets": [
[
119,
131
]
],
"normalized": []
},
{
"id": "837",
"type": "protein_molecule",
"text": [
"CD4"
],
"offsets": [
[
119,
122
]
],
"normalized": []
},
{
"id": "838",
"type": "other_name",
"text": [
"developmental control"
],
"offsets": [
[
163,
184
]
],
"normalized": []
},
{
"id": "839",
"type": "other_name",
"text": [
"CD4 transcription"
],
"offsets": [
[
188,
205
]
],
"normalized": []
},
{
"id": "840",
"type": "protein_molecule",
"text": [
"CD4"
],
"offsets": [
[
188,
191
]
],
"normalized": []
},
{
"id": "841",
"type": "DNA_domain_or_region",
"text": [
"CD4 promoter"
],
"offsets": [
[
248,
260
]
],
"normalized": []
},
{
"id": "842",
"type": "protein_molecule",
"text": [
"CD4"
],
"offsets": [
[
248,
251
]
],
"normalized": []
},
{
"id": "843",
"type": "DNA_domain_or_region",
"text": [
"factor binding sites"
],
"offsets": [
[
270,
290
]
],
"normalized": []
},
{
"id": "844",
"type": "(AND other_name other_name)",
"text": [
"biochemical and mutagenesis analyses"
],
"offsets": [
[
343,
379
]
],
"normalized": []
},
{
"id": "845",
"type": "",
"text": [
"biochemical"
],
"offsets": [
[
343,
354
]
],
"normalized": []
},
{
"id": "846",
"type": "",
"text": [
"mutagenesis"
],
"offsets": [
[
359,
370
]
],
"normalized": []
},
{
"id": "847",
"type": "",
"text": [
"analyses"
],
"offsets": [
[
371,
379
]
],
"normalized": []
},
{
"id": "848",
"type": "protein_family_or_group",
"text": [
"nuclear factors"
],
"offsets": [
[
409,
424
]
],
"normalized": []
},
{
"id": "849",
"type": "DNA_domain_or_region",
"text": [
"initiator-like sequence"
],
"offsets": [
[
480,
503
]
],
"normalized": []
},
{
"id": "850",
"type": "DNA_domain_or_region",
"text": [
"cap site"
],
"offsets": [
[
519,
527
]
],
"normalized": []
},
{
"id": "851",
"type": "DNA_domain_or_region",
"text": [
"Ets consensus sequence"
],
"offsets": [
[
535,
557
]
],
"normalized": []
},
{
"id": "852",
"type": "other_name",
"text": [
"promoter function"
],
"offsets": [
[
580,
597
]
],
"normalized": []
},
{
"id": "853",
"type": "DNA_domain_or_region",
"text": [
"promoter"
],
"offsets": [
[
580,
588
]
],
"normalized": []
},
{
"id": "854",
"type": "protein_molecule",
"text": [
"Myc-associated zinc finger protein"
],
"offsets": [
[
628,
662
]
],
"normalized": []
},
{
"id": "855",
"type": "protein_substructure",
"text": [
"zinc finger"
],
"offsets": [
[
643,
654
]
],
"normalized": []
},
{
"id": "856",
"type": "protein_molecule",
"text": [
"MAZ"
],
"offsets": [
[
664,
667
]
],
"normalized": []
},
{
"id": "857",
"type": "protein_family_or_group",
"text": [
"predominant factor"
],
"offsets": [
[
687,
705
]
],
"normalized": []
},
{
"id": "858",
"type": "DNA_domain_or_region",
"text": [
"ME1a1 G3AG4AG3 motif"
],
"offsets": [
[
774,
794
]
],
"normalized": []
},
{
"id": "859",
"type": "DNA_domain_or_region",
"text": [
"P2 promoter"
],
"offsets": [
[
844,
855
]
],
"normalized": []
},
{
"id": "860",
"type": "DNA_domain_or_region",
"text": [
"c-myc gene"
],
"offsets": [
[
863,
873
]
],
"normalized": []
},
{
"id": "861",
"type": "protein_family_or_group",
"text": [
"MAZ transcription factor"
],
"offsets": [
[
905,
929
]
],
"normalized": []
},
{
"id": "862",
"type": "protein_molecule",
"text": [
"MAZ"
],
"offsets": [
[
905,
908
]
],
"normalized": []
},
{
"id": "863",
"type": "other_name",
"text": [
"developmental expression"
],
"offsets": [
[
989,
1013
]
],
"normalized": []
},
{
"id": "864",
"type": "DNA_domain_or_region",
"text": [
"CD4 gene"
],
"offsets": [
[
1021,
1029
]
],
"normalized": []
},
{
"id": "865",
"type": "protein_molecule",
"text": [
"CD4"
],
"offsets": [
[
1021,
1024
]
],
"normalized": []
}
] | [] | [] | [] |
866 | 95263486 | [
{
"id": "867",
"type": "title",
"text": [
"Erythropoietin stimulates transcription of the TAL1/SCL gene and phosphorylation of its protein products."
],
"offsets": [
[
0,
105
]
]
},
{
"id": "868",
"type": "abstract",
"text": [
"Activation of the TAL1 (or SCL) gene, originally identified through its involvement by a recurrent chromosomal translocation, is the most frequent molecular lesion recognized in T-cell acute lymphoblastic leukemia. The protein products of this gene contain the basic-helix-loop-helix motif characteristic of a large family of transcription factors that bind to the canonical DNA sequence CANNTG as protein heterodimers. TAL1 expression by erythroid cells in vivo and in chemical-induced erythroleukemia cell lines in vivo suggested the gene might regulate aspects of erythroid differentiation. Since the terminal events of erythropoiesis are controlled by the glycoprotein hormone erythropoietin (Epo), we investigated whether the expression or activity of the TAL1 gene and its protein products were affected by Epo in splenic erythroblasts from mice infected with an anemia-inducing strain of Friend virus (FVA cells). Epo elicited a rapid, dose-related increase in TAL1 mRNA by increasing transcription of the gene and stabilizing one of its mRNAs. An Epo-inducible TAL1 DNA binding activity was identified in FVA cell nuclear extracts that subsequently decayed despite accumulating mRNA and protein. Induction of DNA binding activity was associated temporally with Epo-induced phosphorylation of nuclear TAL1 protein. These results indicate that Epo acts at both transcriptional and posttranscriptional levels on the TAL1 locus in Friend virus-induced erythroblasts and establish a link between Epo signaling mechanisms and a member of a family of transcription factors involved in the differentiation of diverse cell lineages."
],
"offsets": [
[
106,
1737
]
]
}
] | [
{
"id": "869",
"type": "protein_molecule",
"text": [
"Erythropoietin"
],
"offsets": [
[
0,
14
]
],
"normalized": []
},
{
"id": "870",
"type": "DNA_domain_or_region",
"text": [
"TAL1/SCL gene"
],
"offsets": [
[
47,
60
]
],
"normalized": []
},
{
"id": "871",
"type": "other_name",
"text": [
"phosphorylation"
],
"offsets": [
[
65,
80
]
],
"normalized": []
},
{
"id": "872",
"type": "protein_domain_or_region",
"text": [
"protein products"
],
"offsets": [
[
88,
104
]
],
"normalized": []
},
{
"id": "873",
"type": "DNA_domain_or_region",
"text": [
"TAL1 (or SCL) gene"
],
"offsets": [
[
124,
142
]
],
"normalized": []
},
{
"id": "874",
"type": "other_name",
"text": [
"recurrent chromosomal translocation"
],
"offsets": [
[
195,
230
]
],
"normalized": []
},
{
"id": "875",
"type": "DNA_N/A",
"text": [
"molecular lesion"
],
"offsets": [
[
253,
269
]
],
"normalized": []
},
{
"id": "876",
"type": "other_name",
"text": [
"T-cell acute lymphoblastic leukemia"
],
"offsets": [
[
284,
319
]
],
"normalized": []
},
{
"id": "877",
"type": "protein_family_or_group",
"text": [
"protein products"
],
"offsets": [
[
325,
341
]
],
"normalized": []
},
{
"id": "878",
"type": "protein_family_or_group",
"text": [
"basic-helix-loop-helix motif"
],
"offsets": [
[
367,
395
]
],
"normalized": []
},
{
"id": "879",
"type": "protein_family_or_group",
"text": [
"transcription factors"
],
"offsets": [
[
432,
453
]
],
"normalized": []
},
{
"id": "880",
"type": "DNA_domain_or_region",
"text": [
"canonical DNA sequence CANNTG"
],
"offsets": [
[
471,
500
]
],
"normalized": []
},
{
"id": "881",
"type": "protein_family_or_group",
"text": [
"protein heterodimers"
],
"offsets": [
[
504,
524
]
],
"normalized": []
},
{
"id": "882",
"type": "other_name",
"text": [
"TAL1 expression"
],
"offsets": [
[
526,
541
]
],
"normalized": []
},
{
"id": "883",
"type": "protein_molecule",
"text": [
"TAL1"
],
"offsets": [
[
526,
530
]
],
"normalized": []
},
{
"id": "884",
"type": "cell_type",
"text": [
"erythroid cells"
],
"offsets": [
[
545,
560
]
],
"normalized": []
},
{
"id": "885",
"type": "cell_line",
"text": [
"chemical-induced erythroleukemia cell lines"
],
"offsets": [
[
576,
619
]
],
"normalized": []
},
{
"id": "886",
"type": "other_name",
"text": [
"erythroid differentiation"
],
"offsets": [
[
673,
698
]
],
"normalized": []
},
{
"id": "887",
"type": "other_name",
"text": [
"erythropoiesis"
],
"offsets": [
[
729,
743
]
],
"normalized": []
},
{
"id": "888",
"type": "protein_molecule",
"text": [
"glycoprotein hormone erythropoietin"
],
"offsets": [
[
766,
801
]
],
"normalized": []
},
{
"id": "889",
"type": "protein_molecule",
"text": [
"Epo"
],
"offsets": [
[
803,
806
]
],
"normalized": []
},
{
"id": "890",
"type": "DNA_domain_or_region",
"text": [
"TAL1 gene"
],
"offsets": [
[
867,
876
]
],
"normalized": []
},
{
"id": "891",
"type": "protein_molecule",
"text": [
"TAL1"
],
"offsets": [
[
867,
871
]
],
"normalized": []
},
{
"id": "892",
"type": "protein_family_or_group",
"text": [
"protein products"
],
"offsets": [
[
885,
901
]
],
"normalized": []
},
{
"id": "893",
"type": "protein_molecule",
"text": [
"Epo"
],
"offsets": [
[
919,
922
]
],
"normalized": []
},
{
"id": "894",
"type": "cell_type",
"text": [
"splenic erythroblasts"
],
"offsets": [
[
926,
947
]
],
"normalized": []
},
{
"id": "895",
"type": "multi_cell",
"text": [
"mice"
],
"offsets": [
[
953,
957
]
],
"normalized": []
},
{
"id": "896",
"type": "protein_molecule",
"text": [
"Epo"
],
"offsets": [
[
1027,
1030
]
],
"normalized": []
},
{
"id": "897",
"type": "RNA_family_or_group",
"text": [
"TAL1 mRNA"
],
"offsets": [
[
1074,
1083
]
],
"normalized": []
},
{
"id": "898",
"type": "protein_molecule",
"text": [
"TAL1"
],
"offsets": [
[
1074,
1078
]
],
"normalized": []
},
{
"id": "899",
"type": "other_name",
"text": [
"transcription"
],
"offsets": [
[
1098,
1111
]
],
"normalized": []
},
{
"id": "900",
"type": "RNA_family_or_group",
"text": [
"mRNAs"
],
"offsets": [
[
1151,
1156
]
],
"normalized": []
},
{
"id": "901",
"type": "other_name",
"text": [
"Epo-inducible TAL1 DNA binding activity"
],
"offsets": [
[
1161,
1200
]
],
"normalized": []
},
{
"id": "902",
"type": "protein_molecule",
"text": [
"Epo"
],
"offsets": [
[
1161,
1164
]
],
"normalized": []
},
{
"id": "903",
"type": "protein_molecule",
"text": [
"TAL1"
],
"offsets": [
[
1175,
1179
]
],
"normalized": []
},
{
"id": "904",
"type": "cell_component",
"text": [
"FVA cell nuclear extracts"
],
"offsets": [
[
1219,
1244
]
],
"normalized": []
},
{
"id": "905",
"type": "RNA_family_or_group",
"text": [
"mRNA"
],
"offsets": [
[
1292,
1296
]
],
"normalized": []
},
{
"id": "906",
"type": "protein_N/A",
"text": [
"protein"
],
"offsets": [
[
1301,
1308
]
],
"normalized": []
},
{
"id": "907",
"type": "other_name",
"text": [
"DNA binding activity"
],
"offsets": [
[
1323,
1343
]
],
"normalized": []
},
{
"id": "908",
"type": "other_name",
"text": [
"Epo-induced phosphorylation"
],
"offsets": [
[
1375,
1402
]
],
"normalized": []
},
{
"id": "909",
"type": "protein_molecule",
"text": [
"Epo"
],
"offsets": [
[
1375,
1378
]
],
"normalized": []
},
{
"id": "910",
"type": "other_name",
"text": [
"phosphorylation"
],
"offsets": [
[
1387,
1402
]
],
"normalized": []
},
{
"id": "911",
"type": "protein_molecule",
"text": [
"nuclear TAL1 protein"
],
"offsets": [
[
1406,
1426
]
],
"normalized": []
},
{
"id": "912",
"type": "protein_molecule",
"text": [
"TAL1"
],
"offsets": [
[
1414,
1418
]
],
"normalized": []
},
{
"id": "913",
"type": "protein_molecule",
"text": [
"Epo"
],
"offsets": [
[
1456,
1459
]
],
"normalized": []
},
{
"id": "914",
"type": "(AND other_name other_name)",
"text": [
"transcriptional and posttranscriptional levels"
],
"offsets": [
[
1473,
1519
]
],
"normalized": []
},
{
"id": "915",
"type": "",
"text": [
"transcriptional"
],
"offsets": [
[
1473,
1488
]
],
"normalized": []
},
{
"id": "916",
"type": "",
"text": [
"posttranscriptional"
],
"offsets": [
[
1493,
1512
]
],
"normalized": []
},
{
"id": "917",
"type": "",
"text": [
"levels"
],
"offsets": [
[
1513,
1519
]
],
"normalized": []
},
{
"id": "918",
"type": "protein_molecule",
"text": [
"TAL1"
],
"offsets": [
[
1527,
1531
]
],
"normalized": []
},
{
"id": "919",
"type": "cell_line",
"text": [
"Friend virus-induced erythroblasts"
],
"offsets": [
[
1541,
1575
]
],
"normalized": []
},
{
"id": "920",
"type": "virus",
"text": [
"Friend virus"
],
"offsets": [
[
1541,
1553
]
],
"normalized": []
},
{
"id": "921",
"type": "other_name",
"text": [
"Epo signaling mechanisms"
],
"offsets": [
[
1605,
1629
]
],
"normalized": []
},
{
"id": "922",
"type": "protein_molecule",
"text": [
"Epo"
],
"offsets": [
[
1605,
1608
]
],
"normalized": []
},
{
"id": "923",
"type": "protein_family_or_group",
"text": [
"transcription factors"
],
"offsets": [
[
1658,
1679
]
],
"normalized": []
},
{
"id": "924",
"type": "cell_type",
"text": [
"diverse cell lineages"
],
"offsets": [
[
1715,
1736
]
],
"normalized": []
}
] | [] | [] | [] |
925 | 95397944 | [
{
"id": "926",
"type": "title",
"text": [
"Nonradioactive quantification of glucocorticoid receptor expression during differentiation of human monocytic cells (U937)."
],
"offsets": [
[
0,
123
]
]
},
{
"id": "927",
"type": "abstract",
"text": [
"We describe a method for relative quantification of specific mRNA using a nonradioactive assay based on DNA strand competition between identical sequences of biotin- and fluorescein-labeled amplicon (probe) and unlabeled amplicon (target) during hybridization. As the target quantity increased, that of the double-labeled probe decreased in accordance with the mass action law. This technique was successfully applied to evaluate differences in glucocorticoid receptor expression in U937 cells before and after the addition of potent differentiation inducers: 12-O-tetradecanoylphorbol 13-acetate (TPA) and a combination of all-trans retinoic acid (RA) and 1,25-dihydroxyvitamin D2 (VD). We observed that TPA treatment was associated with an increase in specific binding of [3H]dexamethasone and up-regulation of GR mRNA while no enhanced GR expression was perceived with RA/VD treatment."
],
"offsets": [
[
124,
1012
]
]
}
] | [
{
"id": "928",
"type": "other_name",
"text": [
"Nonradioactive quantification"
],
"offsets": [
[
0,
29
]
],
"normalized": []
},
{
"id": "929",
"type": "other_name",
"text": [
"glucocorticoid receptor expression"
],
"offsets": [
[
33,
67
]
],
"normalized": []
},
{
"id": "930",
"type": "protein_domain_or_region",
"text": [
"glucocorticoid receptor"
],
"offsets": [
[
33,
56
]
],
"normalized": []
},
{
"id": "931",
"type": "cell_type",
"text": [
"monocytic cells"
],
"offsets": [
[
100,
115
]
],
"normalized": []
},
{
"id": "932",
"type": "cell_line",
"text": [
"U937"
],
"offsets": [
[
117,
121
]
],
"normalized": []
},
{
"id": "933",
"type": "RNA_family_or_group",
"text": [
"mRNA"
],
"offsets": [
[
185,
189
]
],
"normalized": []
},
{
"id": "934",
"type": "other_name",
"text": [
"nonradioactive assay"
],
"offsets": [
[
198,
218
]
],
"normalized": []
},
{
"id": "935",
"type": "other_name",
"text": [
"DNA strand competition"
],
"offsets": [
[
228,
250
]
],
"normalized": []
},
{
"id": "936",
"type": "other_organic_compound",
"text": [
"biotin- and fluorescein-labeled amplicon"
],
"offsets": [
[
282,
322
]
],
"normalized": []
},
{
"id": "937",
"type": "other_organic_compound",
"text": [
"unlabeled amplicon"
],
"offsets": [
[
335,
353
]
],
"normalized": []
},
{
"id": "938",
"type": "other_name",
"text": [
"hybridization"
],
"offsets": [
[
370,
383
]
],
"normalized": []
},
{
"id": "939",
"type": "other_organic_compound",
"text": [
"double-labeled probe"
],
"offsets": [
[
431,
451
]
],
"normalized": []
},
{
"id": "940",
"type": "other_name",
"text": [
"glucocorticoid receptor expression"
],
"offsets": [
[
569,
603
]
],
"normalized": []
},
{
"id": "941",
"type": "protein_domain_or_region",
"text": [
"glucocorticoid receptor"
],
"offsets": [
[
569,
592
]
],
"normalized": []
},
{
"id": "942",
"type": "cell_line",
"text": [
"U937 cells"
],
"offsets": [
[
607,
617
]
],
"normalized": []
},
{
"id": "943",
"type": "other_name",
"text": [
"differentiation inducers"
],
"offsets": [
[
658,
682
]
],
"normalized": []
},
{
"id": "944",
"type": "other_organic_compound",
"text": [
"12-O-tetradecanoylphorbol 13-acetate"
],
"offsets": [
[
684,
720
]
],
"normalized": []
},
{
"id": "945",
"type": "other_organic_compound",
"text": [
"TPA"
],
"offsets": [
[
722,
725
]
],
"normalized": []
},
{
"id": "946",
"type": "other_organic_compound",
"text": [
"all-trans retinoic acid"
],
"offsets": [
[
748,
771
]
],
"normalized": []
},
{
"id": "947",
"type": "other_organic_compound",
"text": [
"RA"
],
"offsets": [
[
773,
775
]
],
"normalized": []
},
{
"id": "948",
"type": "other_organic_compound",
"text": [
"1,25-dihydroxyvitamin D2"
],
"offsets": [
[
781,
805
]
],
"normalized": []
},
{
"id": "949",
"type": "other_organic_compound",
"text": [
"VD"
],
"offsets": [
[
807,
809
]
],
"normalized": []
},
{
"id": "950",
"type": "other_organic_compound",
"text": [
"TPA"
],
"offsets": [
[
829,
832
]
],
"normalized": []
},
{
"id": "951",
"type": "lipid",
"text": [
"[3H]dexamethasone"
],
"offsets": [
[
898,
915
]
],
"normalized": []
},
{
"id": "952",
"type": "RNA_family_or_group",
"text": [
"GR mRNA"
],
"offsets": [
[
937,
944
]
],
"normalized": []
},
{
"id": "953",
"type": "protein_family_or_group",
"text": [
"GR"
],
"offsets": [
[
937,
939
]
],
"normalized": []
},
{
"id": "954",
"type": "other_name",
"text": [
"GR expression"
],
"offsets": [
[
963,
976
]
],
"normalized": []
},
{
"id": "955",
"type": "protein_family_or_group",
"text": [
"GR"
],
"offsets": [
[
963,
965
]
],
"normalized": []
},
{
"id": "956",
"type": "other_name",
"text": [
"RA/VD treatment"
],
"offsets": [
[
996,
1011
]
],
"normalized": []
}
] | [] | [] | [] |
957 | 95266282 | [
{
"id": "958",
"type": "title",
"text": [
"Induction of Sp1 phosphorylation and NF-kappa B-independent HIV promoter domain activity in T lymphocytes stimulated by okadaic acid."
],
"offsets": [
[
0,
133
]
]
},
{
"id": "959",
"type": "abstract",
"text": [
"In contrast to the purely enhancer-dependent effect of cytokines such as TNF on the activity of the HIV regulatory region (LTR), we observed that okadaic acid (OKA) activates HIV transcription through both the enhancer, responding to the factor NF-kappa B, and the promoter domain of the LTR. The inducibility of HIV LTR-driven luciferase expression constructs in lymphoblastoid cells stimulated by OKA depended on both functional Sp1 binding elements and the ability of the TATA box to bind the protein TBP. In both transformed and normal lymphocytes, OKA stimulation induced intense phosphorylation of the constitutively expressed Sp1 protein in the nucleus, a property of OKA not shared by TNF, phorbol ester, or PHA and interleukin 2. Responsiveness of LTR constructs deleted of kappa B elements to HIV Tat expression was increased upon OKA but not TNF stimulation. Our results suggest that SP1 phosphorylation induced by OKA, a selective inhibitor of the serine-threonine phosphatase PP2A, facilitates the formation of a transcription complex involving general transcription factors, HIV Tat, and Sp1 proteins. The formation of this complex would increase, independently of an in synergy with NF-kappa B, the low basal activity of the HIV LTR observed in normal T lymphocytes."
],
"offsets": [
[
134,
1415
]
]
}
] | [
{
"id": "960",
"type": "other_name",
"text": [
"Sp1 phosphorylation"
],
"offsets": [
[
13,
32
]
],
"normalized": []
},
{
"id": "961",
"type": "protein_molecule",
"text": [
"Sp1"
],
"offsets": [
[
13,
16
]
],
"normalized": []
},
{
"id": "962",
"type": "other_name",
"text": [
"phosphorylation"
],
"offsets": [
[
17,
32
]
],
"normalized": []
},
{
"id": "963",
"type": "other_name",
"text": [
"NF-kappa B-independent HIV promoter domain activity"
],
"offsets": [
[
37,
88
]
],
"normalized": []
},
{
"id": "964",
"type": "DNA_domain_or_region",
"text": [
"NF-kappa B-independent HIV promoter"
],
"offsets": [
[
37,
72
]
],
"normalized": []
},
{
"id": "965",
"type": "protein_molecule",
"text": [
"NF-kappa B"
],
"offsets": [
[
37,
47
]
],
"normalized": []
},
{
"id": "966",
"type": "virus",
"text": [
"HIV"
],
"offsets": [
[
60,
63
]
],
"normalized": []
},
{
"id": "967",
"type": "cell_type",
"text": [
"T lymphocytes"
],
"offsets": [
[
92,
105
]
],
"normalized": []
},
{
"id": "968",
"type": "other_organic_compound",
"text": [
"okadaic acid"
],
"offsets": [
[
120,
132
]
],
"normalized": []
},
{
"id": "969",
"type": "other_name",
"text": [
"enhancer-dependent effect"
],
"offsets": [
[
160,
185
]
],
"normalized": []
},
{
"id": "970",
"type": "protein_family_or_group",
"text": [
"cytokines"
],
"offsets": [
[
189,
198
]
],
"normalized": []
},
{
"id": "971",
"type": "protein_family_or_group",
"text": [
"TNF"
],
"offsets": [
[
207,
210
]
],
"normalized": []
},
{
"id": "972",
"type": "DNA_domain_or_region",
"text": [
"HIV regulatory region"
],
"offsets": [
[
234,
255
]
],
"normalized": []
},
{
"id": "973",
"type": "virus",
"text": [
"HIV"
],
"offsets": [
[
234,
237
]
],
"normalized": []
},
{
"id": "974",
"type": "DNA_domain_or_region",
"text": [
"LTR"
],
"offsets": [
[
257,
260
]
],
"normalized": []
},
{
"id": "975",
"type": "other_organic_compound",
"text": [
"okadaic acid"
],
"offsets": [
[
280,
292
]
],
"normalized": []
},
{
"id": "976",
"type": "other_organic_compound",
"text": [
"OKA"
],
"offsets": [
[
294,
297
]
],
"normalized": []
},
{
"id": "977",
"type": "other_name",
"text": [
"HIV transcription"
],
"offsets": [
[
309,
326
]
],
"normalized": []
},
{
"id": "978",
"type": "virus",
"text": [
"HIV"
],
"offsets": [
[
309,
312
]
],
"normalized": []
},
{
"id": "979",
"type": "protein_molecule",
"text": [
"NF-kappa B"
],
"offsets": [
[
379,
389
]
],
"normalized": []
},
{
"id": "980",
"type": "DNA_domain_or_region",
"text": [
"promoter domain"
],
"offsets": [
[
399,
414
]
],
"normalized": []
},
{
"id": "981",
"type": "DNA_domain_or_region",
"text": [
"LTR"
],
"offsets": [
[
422,
425
]
],
"normalized": []
},
{
"id": "982",
"type": "DNA_family_or_group",
"text": [
"HIV LTR-driven luciferase expression constructs"
],
"offsets": [
[
447,
494
]
],
"normalized": []
},
{
"id": "983",
"type": "DNA_domain_or_region",
"text": [
"HIV LTR"
],
"offsets": [
[
447,
454
]
],
"normalized": []
},
{
"id": "984",
"type": "virus",
"text": [
"HIV"
],
"offsets": [
[
447,
450
]
],
"normalized": []
},
{
"id": "985",
"type": "protein_molecule",
"text": [
"luciferase"
],
"offsets": [
[
462,
472
]
],
"normalized": []
},
{
"id": "986",
"type": "cell_type",
"text": [
"lymphoblastoid cells"
],
"offsets": [
[
498,
518
]
],
"normalized": []
},
{
"id": "987",
"type": "other_organic_compound",
"text": [
"OKA"
],
"offsets": [
[
533,
536
]
],
"normalized": []
},
{
"id": "988",
"type": "DNA_domain_or_region",
"text": [
"functional Sp1 binding elements"
],
"offsets": [
[
554,
585
]
],
"normalized": []
},
{
"id": "989",
"type": "protein_molecule",
"text": [
"Sp1"
],
"offsets": [
[
565,
568
]
],
"normalized": []
},
{
"id": "990",
"type": "DNA_domain_or_region",
"text": [
"TATA box"
],
"offsets": [
[
609,
617
]
],
"normalized": []
},
{
"id": "991",
"type": "protein_molecule",
"text": [
"TBP"
],
"offsets": [
[
638,
641
]
],
"normalized": []
},
{
"id": "992",
"type": "(AND cell_type cell_type)",
"text": [
"transformed and normal lymphocytes"
],
"offsets": [
[
651,
685
]
],
"normalized": []
},
{
"id": "993",
"type": "",
"text": [
"transformed"
],
"offsets": [
[
651,
662
]
],
"normalized": []
},
{
"id": "994",
"type": "",
"text": [
"normal"
],
"offsets": [
[
667,
673
]
],
"normalized": []
},
{
"id": "995",
"type": "",
"text": [
"lymphocytes"
],
"offsets": [
[
674,
685
]
],
"normalized": []
},
{
"id": "996",
"type": "other_name",
"text": [
"OKA stimulation"
],
"offsets": [
[
687,
702
]
],
"normalized": []
},
{
"id": "997",
"type": "other_organic_compound",
"text": [
"OKA"
],
"offsets": [
[
687,
690
]
],
"normalized": []
},
{
"id": "998",
"type": "other_name",
"text": [
"phosphorylation"
],
"offsets": [
[
719,
734
]
],
"normalized": []
},
{
"id": "999",
"type": "protein_molecule",
"text": [
"Sp1 protein"
],
"offsets": [
[
767,
778
]
],
"normalized": []
},
{
"id": "1000",
"type": "protein_molecule",
"text": [
"Sp1"
],
"offsets": [
[
767,
770
]
],
"normalized": []
},
{
"id": "1001",
"type": "cell_component",
"text": [
"nucleus"
],
"offsets": [
[
786,
793
]
],
"normalized": []
},
{
"id": "1002",
"type": "other_organic_compound",
"text": [
"OKA"
],
"offsets": [
[
809,
812
]
],
"normalized": []
},
{
"id": "1003",
"type": "protein_family_or_group",
"text": [
"TNF"
],
"offsets": [
[
827,
830
]
],
"normalized": []
},
{
"id": "1004",
"type": "other_organic_compound",
"text": [
"phorbol ester"
],
"offsets": [
[
832,
845
]
],
"normalized": []
},
{
"id": "1005",
"type": "protein_molecule",
"text": [
"PHA"
],
"offsets": [
[
850,
853
]
],
"normalized": []
},
{
"id": "1006",
"type": "protein_molecule",
"text": [
"interleukin 2"
],
"offsets": [
[
858,
871
]
],
"normalized": []
},
{
"id": "1007",
"type": "DNA_family_or_group",
"text": [
"LTR constructs"
],
"offsets": [
[
891,
905
]
],
"normalized": []
},
{
"id": "1008",
"type": "DNA_family_or_group",
"text": [
"kappa B elements"
],
"offsets": [
[
917,
933
]
],
"normalized": []
},
{
"id": "1009",
"type": "other_name",
"text": [
"HIV Tat expression"
],
"offsets": [
[
937,
955
]
],
"normalized": []
},
{
"id": "1010",
"type": "protein_molecule",
"text": [
"HIV Tat"
],
"offsets": [
[
937,
944
]
],
"normalized": []
},
{
"id": "1011",
"type": "virus",
"text": [
"HIV"
],
"offsets": [
[
937,
940
]
],
"normalized": []
},
{
"id": "1012",
"type": "(BUT_NOT other_name other_name)",
"text": [
"OKA but not TNF stimulation"
],
"offsets": [
[
975,
1002
]
],
"normalized": []
},
{
"id": "1013",
"type": "other_organic_compound",
"text": [
"OKA"
],
"offsets": [
[
975,
978
]
],
"normalized": []
},
{
"id": "1014",
"type": "",
"text": [
"OKA"
],
"offsets": [
[
975,
978
]
],
"normalized": []
},
{
"id": "1015",
"type": "protein_family_or_group",
"text": [
"TNF"
],
"offsets": [
[
987,
990
]
],
"normalized": []
},
{
"id": "1016",
"type": "",
"text": [
"TNF"
],
"offsets": [
[
987,
990
]
],
"normalized": []
},
{
"id": "1017",
"type": "",
"text": [
"stimulation"
],
"offsets": [
[
991,
1002
]
],
"normalized": []
},
{
"id": "1018",
"type": "protein_molecule",
"text": [
"SP1"
],
"offsets": [
[
1029,
1032
]
],
"normalized": []
},
{
"id": "1019",
"type": "other_name",
"text": [
"phosphorylation"
],
"offsets": [
[
1033,
1048
]
],
"normalized": []
},
{
"id": "1020",
"type": "other_organic_compound",
"text": [
"OKA"
],
"offsets": [
[
1060,
1063
]
],
"normalized": []
},
{
"id": "1021",
"type": "protein_family_or_group",
"text": [
"serine-threonine phosphatase"
],
"offsets": [
[
1094,
1122
]
],
"normalized": []
},
{
"id": "1022",
"type": "protein_molecule",
"text": [
"PP2A"
],
"offsets": [
[
1123,
1127
]
],
"normalized": []
},
{
"id": "1023",
"type": "protein_complex",
"text": [
"transcription complex"
],
"offsets": [
[
1160,
1181
]
],
"normalized": []
},
{
"id": "1024",
"type": "protein_family_or_group",
"text": [
"transcription factors"
],
"offsets": [
[
1200,
1221
]
],
"normalized": []
},
{
"id": "1025",
"type": "protein_molecule",
"text": [
"HIV Tat"
],
"offsets": [
[
1223,
1230
]
],
"normalized": []
},
{
"id": "1026",
"type": "virus",
"text": [
"HIV"
],
"offsets": [
[
1223,
1226
]
],
"normalized": []
},
{
"id": "1027",
"type": "protein_family_or_group",
"text": [
"Sp1 proteins"
],
"offsets": [
[
1236,
1248
]
],
"normalized": []
},
{
"id": "1028",
"type": "protein_molecule",
"text": [
"Sp1"
],
"offsets": [
[
1236,
1239
]
],
"normalized": []
},
{
"id": "1029",
"type": "protein_molecule",
"text": [
"NF-kappa B"
],
"offsets": [
[
1332,
1342
]
],
"normalized": []
},
{
"id": "1030",
"type": "other_name",
"text": [
"basal activity"
],
"offsets": [
[
1352,
1366
]
],
"normalized": []
},
{
"id": "1031",
"type": "DNA_domain_or_region",
"text": [
"HIV LTR"
],
"offsets": [
[
1374,
1381
]
],
"normalized": []
},
{
"id": "1032",
"type": "virus",
"text": [
"HIV"
],
"offsets": [
[
1374,
1377
]
],
"normalized": []
},
{
"id": "1033",
"type": "cell_type",
"text": [
"normal T lymphocytes"
],
"offsets": [
[
1394,
1414
]
],
"normalized": []
},
{
"id": "1034",
"type": "cell_type",
"text": [
"T lymphocytes"
],
"offsets": [
[
1401,
1414
]
],
"normalized": []
}
] | [] | [] | [] |
1035 | 95236293 | [
{
"id": "1036",
"type": "title",
"text": [
"The role of shared receptor motifs and common Stat proteins in the generation of cytokine pleiotropy and redundancy by IL-2, IL-4, IL-7, IL-13, and IL-15."
],
"offsets": [
[
0,
154
]
]
},
{
"id": "1037",
"type": "abstract",
"text": [
"To understand the molecular bases for cytokine redundancy and pleiotropy, we have compared the Stat proteins activated in peripheral blood lymphocytes (PBLs) by cytokines with shared and distinct actions. Interleukin-2 (IL-2) rapidly activated Stat5 in fresh PBL, and Stat3 and Stat5 in preactivated PBL. IL-7 and IL-15 induced the same complexes as IL-2, a feature explained by the existence of similar tyrosine-phosphorylated motifs in the cytoplasmic domains of IL-2R beta and IL-7R that can serve as docking sites for Stat proteins. IL-13 Induced the same complexes as IL-4, a finding explained by our studies implicating IL-4R as a shared component of the receptors. These studies demonstrate that a single cytokine can activate different combinations of Stat proteins under different physiological conditions, and also indicate two mechanisms by which distinct cytokines can activate the same Stat protein."
],
"offsets": [
[
155,
1067
]
]
}
] | [
{
"id": "1038",
"type": "protein_substructure",
"text": [
"shared receptor motifs"
],
"offsets": [
[
12,
34
]
],
"normalized": []
},
{
"id": "1039",
"type": "protein_family_or_group",
"text": [
"common Stat proteins"
],
"offsets": [
[
39,
59
]
],
"normalized": []
},
{
"id": "1040",
"type": "other_name",
"text": [
"cytokine pleiotropy"
],
"offsets": [
[
81,
100
]
],
"normalized": []
},
{
"id": "1041",
"type": "protein_family_or_group",
"text": [
"cytokine"
],
"offsets": [
[
81,
89
]
],
"normalized": []
},
{
"id": "1042",
"type": "protein_molecule",
"text": [
"IL-2"
],
"offsets": [
[
119,
123
]
],
"normalized": []
},
{
"id": "1043",
"type": "protein_molecule",
"text": [
"IL-4"
],
"offsets": [
[
125,
129
]
],
"normalized": []
},
{
"id": "1044",
"type": "protein_molecule",
"text": [
"IL-7"
],
"offsets": [
[
131,
135
]
],
"normalized": []
},
{
"id": "1045",
"type": "protein_molecule",
"text": [
"IL-13"
],
"offsets": [
[
137,
142
]
],
"normalized": []
},
{
"id": "1046",
"type": "protein_molecule",
"text": [
"IL-15"
],
"offsets": [
[
148,
153
]
],
"normalized": []
},
{
"id": "1047",
"type": "(AND other_name other_name)",
"text": [
"cytokine redundancy and pleiotropy"
],
"offsets": [
[
193,
227
]
],
"normalized": []
},
{
"id": "1048",
"type": "",
"text": [
"cytokine"
],
"offsets": [
[
193,
201
]
],
"normalized": []
},
{
"id": "1049",
"type": "",
"text": [
"redundancy"
],
"offsets": [
[
202,
212
]
],
"normalized": []
},
{
"id": "1050",
"type": "",
"text": [
"pleiotropy"
],
"offsets": [
[
217,
227
]
],
"normalized": []
},
{
"id": "1051",
"type": "protein_family_or_group",
"text": [
"Stat proteins"
],
"offsets": [
[
250,
263
]
],
"normalized": []
},
{
"id": "1052",
"type": "cell_type",
"text": [
"peripheral blood lymphocytes"
],
"offsets": [
[
277,
305
]
],
"normalized": []
},
{
"id": "1053",
"type": "cell_type",
"text": [
"PBLs"
],
"offsets": [
[
307,
311
]
],
"normalized": []
},
{
"id": "1054",
"type": "protein_family_or_group",
"text": [
"cytokines"
],
"offsets": [
[
316,
325
]
],
"normalized": []
},
{
"id": "1055",
"type": "protein_molecule",
"text": [
"Interleukin-2"
],
"offsets": [
[
360,
373
]
],
"normalized": []
},
{
"id": "1056",
"type": "protein_molecule",
"text": [
"IL-2"
],
"offsets": [
[
375,
379
]
],
"normalized": []
},
{
"id": "1057",
"type": "protein_molecule",
"text": [
"Stat5"
],
"offsets": [
[
399,
404
]
],
"normalized": []
},
{
"id": "1058",
"type": "cell_type",
"text": [
"PBL"
],
"offsets": [
[
414,
417
]
],
"normalized": []
},
{
"id": "1059",
"type": "protein_molecule",
"text": [
"Stat3"
],
"offsets": [
[
423,
428
]
],
"normalized": []
},
{
"id": "1060",
"type": "protein_molecule",
"text": [
"Stat5"
],
"offsets": [
[
433,
438
]
],
"normalized": []
},
{
"id": "1061",
"type": "cell_type",
"text": [
"preactivated PBL"
],
"offsets": [
[
442,
458
]
],
"normalized": []
},
{
"id": "1062",
"type": "protein_molecule",
"text": [
"IL-7"
],
"offsets": [
[
460,
464
]
],
"normalized": []
},
{
"id": "1063",
"type": "protein_molecule",
"text": [
"IL-15"
],
"offsets": [
[
469,
474
]
],
"normalized": []
},
{
"id": "1064",
"type": "protein_molecule",
"text": [
"IL-2"
],
"offsets": [
[
505,
509
]
],
"normalized": []
},
{
"id": "1065",
"type": "protein_substructure",
"text": [
"tyrosine-phosphorylated motifs"
],
"offsets": [
[
559,
589
]
],
"normalized": []
},
{
"id": "1066",
"type": "amino_acid_monomer",
"text": [
"tyrosine"
],
"offsets": [
[
559,
567
]
],
"normalized": []
},
{
"id": "1067",
"type": "protein_domain_or_region",
"text": [
"cytoplasmic domains"
],
"offsets": [
[
597,
616
]
],
"normalized": []
},
{
"id": "1068",
"type": "protein_molecule",
"text": [
"IL-2R beta"
],
"offsets": [
[
620,
630
]
],
"normalized": []
},
{
"id": "1069",
"type": "protein_molecule",
"text": [
"IL-7R"
],
"offsets": [
[
635,
640
]
],
"normalized": []
},
{
"id": "1070",
"type": "protein_family_or_group",
"text": [
"Stat proteins"
],
"offsets": [
[
677,
690
]
],
"normalized": []
},
{
"id": "1071",
"type": "protein_molecule",
"text": [
"IL-13"
],
"offsets": [
[
692,
697
]
],
"normalized": []
},
{
"id": "1072",
"type": "protein_molecule",
"text": [
"IL-4"
],
"offsets": [
[
728,
732
]
],
"normalized": []
},
{
"id": "1073",
"type": "protein_molecule",
"text": [
"IL-4R"
],
"offsets": [
[
781,
786
]
],
"normalized": []
},
{
"id": "1074",
"type": "protein_family_or_group",
"text": [
"receptors"
],
"offsets": [
[
816,
825
]
],
"normalized": []
},
{
"id": "1075",
"type": "protein_family_or_group",
"text": [
"cytokine"
],
"offsets": [
[
867,
875
]
],
"normalized": []
},
{
"id": "1076",
"type": "protein_family_or_group",
"text": [
"Stat proteins"
],
"offsets": [
[
915,
928
]
],
"normalized": []
},
{
"id": "1077",
"type": "other_name",
"text": [
"physiological conditions"
],
"offsets": [
[
945,
969
]
],
"normalized": []
},
{
"id": "1078",
"type": "protein_family_or_group",
"text": [
"cytokines"
],
"offsets": [
[
1022,
1031
]
],
"normalized": []
},
{
"id": "1079",
"type": "protein_family_or_group",
"text": [
"Stat protein"
],
"offsets": [
[
915,
927
]
],
"normalized": []
}
] | [] | [] | [] |
1080 | 95184007 | [
{
"id": "1081",
"type": "title",
"text": [
"Control of I kappa B-alpha proteolysis by site-specific, signal-induced phosphorylation."
],
"offsets": [
[
0,
88
]
]
},
{
"id": "1082",
"type": "abstract",
"text": [
"I kappa B-alpha inhibits transcription factor NF-kappa B by retaining it in the cytoplasm. Various stimuli, typically those associated with stress or pathogens, rapidly inactivate I kappa B-alpha. This liberates NF-kappa B to translocate to the nucleus and initiate transcription of genes important for the defense of the organism. Activation of NF-kappa B correlates with phosphorylation of I kappa B-alpha and requires the proteolysis of this inhibitor. When either serine-32 or serine-36 of I kappa B-alpha was mutated, the protein did not undergo signal-induced phosphorylation or degradation, and NF-kappa B could not be activated. These results suggest that phosphorylation at one or both of these residues is critical for activation of NF-kappa B."
],
"offsets": [
[
89,
843
]
]
}
] | [
{
"id": "1083",
"type": "other_name",
"text": [
"I kappa B-alpha proteolysis"
],
"offsets": [
[
11,
38
]
],
"normalized": []
},
{
"id": "1084",
"type": "protein_molecule",
"text": [
"I kappa B-alpha"
],
"offsets": [
[
11,
26
]
],
"normalized": []
},
{
"id": "1085",
"type": "other_name",
"text": [
"phosphorylation"
],
"offsets": [
[
72,
87
]
],
"normalized": []
},
{
"id": "1086",
"type": "protein_molecule",
"text": [
"I kappa B-alpha"
],
"offsets": [
[
89,
104
]
],
"normalized": []
},
{
"id": "1087",
"type": "protein_family_or_group",
"text": [
"transcription factor"
],
"offsets": [
[
114,
134
]
],
"normalized": []
},
{
"id": "1088",
"type": "protein_molecule",
"text": [
"NF-kappa B"
],
"offsets": [
[
135,
145
]
],
"normalized": []
},
{
"id": "1089",
"type": "cell_component",
"text": [
"cytoplasm"
],
"offsets": [
[
169,
178
]
],
"normalized": []
},
{
"id": "1090",
"type": "protein_molecule",
"text": [
"I kappa B-alpha"
],
"offsets": [
[
269,
284
]
],
"normalized": []
},
{
"id": "1091",
"type": "protein_molecule",
"text": [
"NF-kappa B"
],
"offsets": [
[
301,
311
]
],
"normalized": []
},
{
"id": "1092",
"type": "cell_component",
"text": [
"nucleus"
],
"offsets": [
[
334,
341
]
],
"normalized": []
},
{
"id": "1093",
"type": "other_name",
"text": [
"transcription"
],
"offsets": [
[
355,
368
]
],
"normalized": []
},
{
"id": "1094",
"type": "DNA_family_or_group",
"text": [
"genes"
],
"offsets": [
[
372,
377
]
],
"normalized": []
},
{
"id": "1095",
"type": "protein_molecule",
"text": [
"NF-kappa B"
],
"offsets": [
[
435,
445
]
],
"normalized": []
},
{
"id": "1096",
"type": "other_name",
"text": [
"phosphorylation"
],
"offsets": [
[
462,
477
]
],
"normalized": []
},
{
"id": "1097",
"type": "protein_molecule",
"text": [
"I kappa B-alpha"
],
"offsets": [
[
481,
496
]
],
"normalized": []
},
{
"id": "1098",
"type": "other_name",
"text": [
"proteolysis"
],
"offsets": [
[
514,
525
]
],
"normalized": []
},
{
"id": "1099",
"type": "amino_acid_monomer",
"text": [
"serine-32"
],
"offsets": [
[
557,
566
]
],
"normalized": []
},
{
"id": "1100",
"type": "amino_acid_monomer",
"text": [
"serine-36"
],
"offsets": [
[
570,
579
]
],
"normalized": []
},
{
"id": "1101",
"type": "protein_molecule",
"text": [
"I kappa B-alpha"
],
"offsets": [
[
583,
598
]
],
"normalized": []
},
{
"id": "1102",
"type": "other_name",
"text": [
"signal-induced phosphorylation"
],
"offsets": [
[
640,
670
]
],
"normalized": []
},
{
"id": "1103",
"type": "other_name",
"text": [
"phosphorylation"
],
"offsets": [
[
655,
670
]
],
"normalized": []
},
{
"id": "1104",
"type": "other_name",
"text": [
"degradation"
],
"offsets": [
[
674,
685
]
],
"normalized": []
},
{
"id": "1105",
"type": "protein_molecule",
"text": [
"NF-kappa B"
],
"offsets": [
[
691,
701
]
],
"normalized": []
},
{
"id": "1106",
"type": "other_name",
"text": [
"phosphorylation"
],
"offsets": [
[
753,
768
]
],
"normalized": []
},
{
"id": "1107",
"type": "amino_acid_monomer",
"text": [
"residues"
],
"offsets": [
[
793,
801
]
],
"normalized": []
},
{
"id": "1108",
"type": "protein_molecule",
"text": [
"NF-kappa B"
],
"offsets": [
[
832,
842
]
],
"normalized": []
}
] | [] | [] | [] |
1109 | 95388524 | [
{
"id": "1110",
"type": "title",
"text": [
"Regulation of transcription of the human erythropoietin receptor gene by proteins binding to GATA-1 and Sp1 motifs."
],
"offsets": [
[
0,
115
]
]
},
{
"id": "1111",
"type": "abstract",
"text": [
"Erythropoietin (Epo), the primary regulator of the production of erythroid cells, acts by binding to a cell surface receptor (EpoR) on erythroid progenitors. We used deletion analysis and transfection assays with reporter gene constructs to examine the transcription control elements in the 5' flanking region of the human EpoR gene. In erythroid cells most of the transcription activity was contained in a 150 bp promoter fragment with binding sites for transcription factors AP2, Sp1 and the erythroid-specific GATA-1. The 150 bp hEpoR promoter exhibited high and low activity in erythroid OCIM1 and K562 cells, respectively, reflecting the high and low levels of constitutive hEpoR expression. The GATA-1 and Sp1 binding sites in this promoter lacking a TATA sequence were necessary for a high level of transcription activation. Protein-DNA binding studies suggested that Sp1 and two other CCGCCC binding proteins from erythroid and non-erythroid cells could bind to the Sp1 binding motif. By increasing GATA-1 levels via co-transfection, we were able to transactivate the hEpoR promoter in K562 cells and non-erythroid cells, but not in the highly active OCIM1 cells, although GATA-1 mRNA levels were comparable in OCIM1 and K562. Interestingly, when we mutated the Sp1 site, resulting in a marked decrease in hEpoR promoter activity, we could restore transactivation by increasing GATA-1 levels in OCIM1 cells. These data suggest that while GATA-1 can transactivate the EpoR promoter, the level of hEpoR gene expression does not depend on GATA-1 alone. Rather, hEpoR transcription activity depends on coordination between Sp1 and GATA-1 with other cell-specific factors, including possibly other Sp1-like binding proteins, to provide high level, tissue-specific expression."
],
"offsets": [
[
116,
1894
]
]
}
] | [
{
"id": "1112",
"type": "other_name",
"text": [
"transcription"
],
"offsets": [
[
14,
27
]
],
"normalized": []
},
{
"id": "1113",
"type": "DNA_domain_or_region",
"text": [
"human erythropoietin receptor gene"
],
"offsets": [
[
35,
69
]
],
"normalized": []
},
{
"id": "1114",
"type": "DNA_domain_or_region",
"text": [
"GATA-1 and Sp1 motifs"
],
"offsets": [
[
93,
114
]
],
"normalized": []
},
{
"id": "1115",
"type": "DNA_domain_or_region",
"text": [
"GATA-1"
],
"offsets": [
[
93,
99
]
],
"normalized": []
},
{
"id": "1116",
"type": "DNA_domain_or_region",
"text": [
"Sp1 motifs"
],
"offsets": [
[
104,
114
]
],
"normalized": []
},
{
"id": "1117",
"type": "protein_molecule",
"text": [
"Erythropoietin"
],
"offsets": [
[
116,
130
]
],
"normalized": []
},
{
"id": "1118",
"type": "protein_molecule",
"text": [
"Epo"
],
"offsets": [
[
132,
135
]
],
"normalized": []
},
{
"id": "1119",
"type": "cell_type",
"text": [
"erythroid cells"
],
"offsets": [
[
181,
196
]
],
"normalized": []
},
{
"id": "1120",
"type": "protein_family_or_group",
"text": [
"cell surface receptor"
],
"offsets": [
[
219,
240
]
],
"normalized": []
},
{
"id": "1121",
"type": "protein_molecule",
"text": [
"EpoR"
],
"offsets": [
[
242,
246
]
],
"normalized": []
},
{
"id": "1122",
"type": "cell_type",
"text": [
"erythroid progenitors"
],
"offsets": [
[
251,
272
]
],
"normalized": []
},
{
"id": "1123",
"type": "other_name",
"text": [
"deletion analysis"
],
"offsets": [
[
282,
299
]
],
"normalized": []
},
{
"id": "1124",
"type": "other_name",
"text": [
"transfection assays"
],
"offsets": [
[
304,
323
]
],
"normalized": []
},
{
"id": "1125",
"type": "DNA_family_or_group",
"text": [
"reporter gene constructs"
],
"offsets": [
[
329,
353
]
],
"normalized": []
},
{
"id": "1126",
"type": "DNA_domain_or_region",
"text": [
"transcription control elements"
],
"offsets": [
[
369,
399
]
],
"normalized": []
},
{
"id": "1127",
"type": "DNA_domain_or_region",
"text": [
"5' flanking region"
],
"offsets": [
[
407,
425
]
],
"normalized": []
},
{
"id": "1128",
"type": "DNA_domain_or_region",
"text": [
"human EpoR gene"
],
"offsets": [
[
433,
448
]
],
"normalized": []
},
{
"id": "1129",
"type": "protein_molecule",
"text": [
"EpoR"
],
"offsets": [
[
439,
443
]
],
"normalized": []
},
{
"id": "1130",
"type": "cell_type",
"text": [
"erythroid cells"
],
"offsets": [
[
453,
468
]
],
"normalized": []
},
{
"id": "1131",
"type": "other_name",
"text": [
"transcription activity"
],
"offsets": [
[
481,
503
]
],
"normalized": []
},
{
"id": "1132",
"type": "DNA_domain_or_region",
"text": [
"150 bp promoter"
],
"offsets": [
[
523,
538
]
],
"normalized": []
},
{
"id": "1133",
"type": "DNA_domain_or_region",
"text": [
"binding sites"
],
"offsets": [
[
553,
566
]
],
"normalized": []
},
{
"id": "1134",
"type": "protein_family_or_group",
"text": [
"transcription factors"
],
"offsets": [
[
571,
592
]
],
"normalized": []
},
{
"id": "1135",
"type": "protein_molecule",
"text": [
"AP2"
],
"offsets": [
[
593,
596
]
],
"normalized": []
},
{
"id": "1136",
"type": "protein_molecule",
"text": [
"Sp1"
],
"offsets": [
[
598,
601
]
],
"normalized": []
},
{
"id": "1137",
"type": "protein_molecule",
"text": [
"erythroid-specific GATA-1"
],
"offsets": [
[
610,
635
]
],
"normalized": []
},
{
"id": "1138",
"type": "DNA_domain_or_region",
"text": [
"150 bp hEpoR promoter"
],
"offsets": [
[
641,
662
]
],
"normalized": []
},
{
"id": "1139",
"type": "cell_line",
"text": [
"OCIM1"
],
"offsets": [
[
708,
713
]
],
"normalized": []
},
{
"id": "1140",
"type": "cell_line",
"text": [
"K562 cells"
],
"offsets": [
[
718,
728
]
],
"normalized": []
},
{
"id": "1141",
"type": "other_name",
"text": [
"hEpoR expression"
],
"offsets": [
[
795,
811
]
],
"normalized": []
},
{
"id": "1142",
"type": "protein_molecule",
"text": [
"hEpoR"
],
"offsets": [
[
648,
653
]
],
"normalized": []
},
{
"id": "1143",
"type": "(AND DNA_domain_or_region DNA_domain_or_region)",
"text": [
"GATA-1 and Sp1 binding sites"
],
"offsets": [
[
817,
845
]
],
"normalized": []
},
{
"id": "1144",
"type": "",
"text": [
"GATA-1"
],
"offsets": [
[
817,
823
]
],
"normalized": []
},
{
"id": "1145",
"type": "",
"text": [
"Sp1"
],
"offsets": [
[
828,
831
]
],
"normalized": []
},
{
"id": "1146",
"type": "",
"text": [
"binding sites"
],
"offsets": [
[
832,
845
]
],
"normalized": []
},
{
"id": "1147",
"type": "DNA_domain_or_region",
"text": [
"TATA sequence"
],
"offsets": [
[
873,
886
]
],
"normalized": []
},
{
"id": "1148",
"type": "other_name",
"text": [
"transcription activation"
],
"offsets": [
[
922,
946
]
],
"normalized": []
},
{
"id": "1149",
"type": "other_name",
"text": [
"Protein-DNA binding studies"
],
"offsets": [
[
948,
975
]
],
"normalized": []
},
{
"id": "1150",
"type": "protein_molecule",
"text": [
"Sp1"
],
"offsets": [
[
991,
994
]
],
"normalized": []
},
{
"id": "1151",
"type": "protein_family_or_group",
"text": [
"CCGCCC binding proteins"
],
"offsets": [
[
1009,
1032
]
],
"normalized": []
},
{
"id": "1152",
"type": "(AND cell_type cell_type)",
"text": [
"erythroid and non-erythroid cells"
],
"offsets": [
[
1038,
1071
]
],
"normalized": []
},
{
"id": "1153",
"type": "",
"text": [
"erythroid"
],
"offsets": [
[
1038,
1047
]
],
"normalized": []
},
{
"id": "1154",
"type": "",
"text": [
"non-erythroid"
],
"offsets": [
[
1052,
1065
]
],
"normalized": []
},
{
"id": "1155",
"type": "",
"text": [
"cells"
],
"offsets": [
[
1066,
1071
]
],
"normalized": []
},
{
"id": "1156",
"type": "DNA_domain_or_region",
"text": [
"Sp1 binding motif"
],
"offsets": [
[
1090,
1107
]
],
"normalized": []
},
{
"id": "1157",
"type": "protein_molecule",
"text": [
"Sp1"
],
"offsets": [
[
1090,
1093
]
],
"normalized": []
},
{
"id": "1158",
"type": "other_name",
"text": [
"GATA-1 levels"
],
"offsets": [
[
1123,
1136
]
],
"normalized": []
},
{
"id": "1159",
"type": "protein_molecule",
"text": [
"GATA-1"
],
"offsets": [
[
1123,
1129
]
],
"normalized": []
},
{
"id": "1160",
"type": "other_name",
"text": [
"co-transfection"
],
"offsets": [
[
1141,
1156
]
],
"normalized": []
},
{
"id": "1161",
"type": "DNA_domain_or_region",
"text": [
"hEpoR promoter"
],
"offsets": [
[
1192,
1206
]
],
"normalized": []
},
{
"id": "1162",
"type": "cell_line",
"text": [
"K562 cells"
],
"offsets": [
[
1210,
1220
]
],
"normalized": []
},
{
"id": "1163",
"type": "cell_type",
"text": [
"non-erythroid cells"
],
"offsets": [
[
1225,
1244
]
],
"normalized": []
},
{
"id": "1164",
"type": "cell_type",
"text": [
"OCIM1 cells"
],
"offsets": [
[
1275,
1286
]
],
"normalized": []
},
{
"id": "1165",
"type": "other_name",
"text": [
"GATA-1 mRNA levels"
],
"offsets": [
[
1297,
1315
]
],
"normalized": []
},
{
"id": "1166",
"type": "RNA_molecule",
"text": [
"GATA-1 mRNA"
],
"offsets": [
[
1297,
1308
]
],
"normalized": []
},
{
"id": "1167",
"type": "protein_molecule",
"text": [
"GATA-1"
],
"offsets": [
[
1297,
1303
]
],
"normalized": []
},
{
"id": "1168",
"type": "cell_line",
"text": [
"OCIM1"
],
"offsets": [
[
1275,
1280
]
],
"normalized": []
},
{
"id": "1169",
"type": "cell_line",
"text": [
"K562"
],
"offsets": [
[
1210,
1214
]
],
"normalized": []
},
{
"id": "1170",
"type": "DNA_domain_or_region",
"text": [
"Sp1 site"
],
"offsets": [
[
1386,
1394
]
],
"normalized": []
},
{
"id": "1171",
"type": "protein_molecule",
"text": [
"Sp1"
],
"offsets": [
[
1386,
1389
]
],
"normalized": []
},
{
"id": "1172",
"type": "other_name",
"text": [
"hEpoR promoter activity"
],
"offsets": [
[
1430,
1453
]
],
"normalized": []
},
{
"id": "1173",
"type": "DNA_domain_or_region",
"text": [
"hEpoR promoter"
],
"offsets": [
[
1430,
1444
]
],
"normalized": []
},
{
"id": "1174",
"type": "other_name",
"text": [
"transactivation"
],
"offsets": [
[
1472,
1487
]
],
"normalized": []
},
{
"id": "1175",
"type": "other_name",
"text": [
"GATA-1 levels"
],
"offsets": [
[
1502,
1515
]
],
"normalized": []
},
{
"id": "1176",
"type": "protein_molecule",
"text": [
"GATA-1"
],
"offsets": [
[
1502,
1508
]
],
"normalized": []
},
{
"id": "1177",
"type": "cell_type",
"text": [
"OCIM1 cells"
],
"offsets": [
[
1519,
1530
]
],
"normalized": []
},
{
"id": "1178",
"type": "protein_molecule",
"text": [
"GATA-1"
],
"offsets": [
[
1562,
1568
]
],
"normalized": []
},
{
"id": "1179",
"type": "DNA_domain_or_region",
"text": [
"EpoR promoter"
],
"offsets": [
[
1591,
1604
]
],
"normalized": []
},
{
"id": "1180",
"type": "protein_molecule",
"text": [
"EpoR"
],
"offsets": [
[
1591,
1595
]
],
"normalized": []
},
{
"id": "1181",
"type": "other_name",
"text": [
"hEpoR gene expression"
],
"offsets": [
[
1619,
1640
]
],
"normalized": []
},
{
"id": "1182",
"type": "DNA_domain_or_region",
"text": [
"hEpoR gene"
],
"offsets": [
[
1619,
1629
]
],
"normalized": []
},
{
"id": "1183",
"type": "protein_molecule",
"text": [
"GATA-1"
],
"offsets": [
[
1660,
1666
]
],
"normalized": []
},
{
"id": "1184",
"type": "other_name",
"text": [
"hEpoR transcription activity"
],
"offsets": [
[
1682,
1710
]
],
"normalized": []
},
{
"id": "1185",
"type": "protein_molecule",
"text": [
"hEpoR"
],
"offsets": [
[
1682,
1687
]
],
"normalized": []
},
{
"id": "1186",
"type": "protein_molecule",
"text": [
"Sp1"
],
"offsets": [
[
1743,
1746
]
],
"normalized": []
},
{
"id": "1187",
"type": "protein_molecule",
"text": [
"GATA-1"
],
"offsets": [
[
1751,
1757
]
],
"normalized": []
},
{
"id": "1188",
"type": "protein_family_or_group",
"text": [
"cell-specific factors"
],
"offsets": [
[
1769,
1790
]
],
"normalized": []
},
{
"id": "1189",
"type": "protein_family_or_group",
"text": [
"Sp1-like binding proteins"
],
"offsets": [
[
1817,
1842
]
],
"normalized": []
},
{
"id": "1190",
"type": "protein_molecule",
"text": [
"Sp1"
],
"offsets": [
[
1817,
1820
]
],
"normalized": []
},
{
"id": "1191",
"type": "other_name",
"text": [
"tissue-specific expression"
],
"offsets": [
[
1867,
1893
]
],
"normalized": []
}
] | [] | [] | [] |
1192 | 95365382 | [
{
"id": "1193",
"type": "title",
"text": [
"Overexpression of DR-nm23, a protein encoded by a member of the nm23 gene family, inhibits granulocyte differentiation and induces apoptosis in 32Dc13 myeloid cells."
],
"offsets": [
[
0,
165
]
]
},
{
"id": "1194",
"type": "abstract",
"text": [
"Chronic myelogenous leukemia evolves in two clinically distinct stages: a chronic and a blast crisis phase. The molecular changes associated with chronic phase to blast crisis transition are largely unknown. We have identified a cDNA clone, DR-nm23, differentially expressed in a blast-crisis cDNA library, which has approximately 70% sequence similarity to the putative metastatic suppressor genes, nm23-H1 and nm23-H2. The deduced amino acid sequence similarity to the proteins encoded by these two latter genes is approximately 65% and includes domains and amino acid residues (the leucine zipper-like and the RGD domain, a serine and a histidine residue in the NH2- and in the COOH-terminal portion of the protein, respectively) postulated to be important for nm23 function. DR-nm23 mRNA is preferentially expressed at early stages of myeloid differentiation of highly purified CD34+ cells. Its constitutive expression in the myeloid precursor 32Dc13 cell line, which is growth-factor dependent for both proliferation and differentiation, results in inhibition of granulocytic differentiation induced by granulocyte colony-stimulating factor and causes apoptotic cell death. These results are consistent with a role for DR-nm23 in normal hematopoiesis and raise the possibility that its overexpression contributes to differentiation arrest, a feature of blastic transformation in chronic myelogenous leukemia."
],
"offsets": [
[
166,
1579
]
]
}
] | [
{
"id": "1195",
"type": "protein_molecule",
"text": [
"DR-nm23"
],
"offsets": [
[
18,
25
]
],
"normalized": []
},
{
"id": "1196",
"type": "DNA_family_or_group",
"text": [
"nm23 gene family"
],
"offsets": [
[
64,
80
]
],
"normalized": []
},
{
"id": "1197",
"type": "other_name",
"text": [
"granulocyte differentiation"
],
"offsets": [
[
91,
118
]
],
"normalized": []
},
{
"id": "1198",
"type": "cell_type",
"text": [
"granulocyte"
],
"offsets": [
[
91,
102
]
],
"normalized": []
},
{
"id": "1199",
"type": "other_name",
"text": [
"apoptosis"
],
"offsets": [
[
131,
140
]
],
"normalized": []
},
{
"id": "1200",
"type": "cell_line",
"text": [
"32Dc13 myeloid cells"
],
"offsets": [
[
144,
164
]
],
"normalized": []
},
{
"id": "1201",
"type": "other_name",
"text": [
"Chronic myelogenous leukemia"
],
"offsets": [
[
166,
194
]
],
"normalized": []
},
{
"id": "1202",
"type": "other_name",
"text": [
"chronic"
],
"offsets": [
[
240,
247
]
],
"normalized": []
},
{
"id": "1203",
"type": "other_name",
"text": [
"blast crisis phase"
],
"offsets": [
[
254,
272
]
],
"normalized": []
},
{
"id": "1204",
"type": "other_name",
"text": [
"chronic phase"
],
"offsets": [
[
312,
325
]
],
"normalized": []
},
{
"id": "1205",
"type": "other_name",
"text": [
"blast crisis"
],
"offsets": [
[
329,
341
]
],
"normalized": []
},
{
"id": "1206",
"type": "DNA_family_or_group",
"text": [
"cDNA clone"
],
"offsets": [
[
395,
405
]
],
"normalized": []
},
{
"id": "1207",
"type": "protein_molecule",
"text": [
"DR-nm23"
],
"offsets": [
[
407,
414
]
],
"normalized": []
},
{
"id": "1208",
"type": "DNA_family_or_group",
"text": [
"blast-crisis cDNA library,"
],
"offsets": [
[
446,
472
]
],
"normalized": []
},
{
"id": "1209",
"type": "DNA_family_or_group",
"text": [
"putative metastatic suppressor genes"
],
"offsets": [
[
528,
564
]
],
"normalized": []
},
{
"id": "1210",
"type": "DNA_domain_or_region",
"text": [
"nm23-H1"
],
"offsets": [
[
566,
573
]
],
"normalized": []
},
{
"id": "1211",
"type": "DNA_domain_or_region",
"text": [
"nm23-H2"
],
"offsets": [
[
578,
585
]
],
"normalized": []
},
{
"id": "1212",
"type": "other_name",
"text": [
"amino acid sequence similarity"
],
"offsets": [
[
599,
629
]
],
"normalized": []
},
{
"id": "1213",
"type": "protein_N/A",
"text": [
"amino acid sequence"
],
"offsets": [
[
599,
618
]
],
"normalized": []
},
{
"id": "1214",
"type": "amino_acid_monomer",
"text": [
"amino acid residues"
],
"offsets": [
[
726,
745
]
],
"normalized": []
},
{
"id": "1215",
"type": "protein_domain_or_region",
"text": [
"leucine zipper-like"
],
"offsets": [
[
751,
770
]
],
"normalized": []
},
{
"id": "1216",
"type": "protein_domain_or_region",
"text": [
"RGD domain"
],
"offsets": [
[
779,
789
]
],
"normalized": []
},
{
"id": "1217",
"type": "amino_acid_monomer",
"text": [
"serine"
],
"offsets": [
[
793,
799
]
],
"normalized": []
},
{
"id": "1218",
"type": "amino_acid_monomer",
"text": [
"histidine"
],
"offsets": [
[
806,
815
]
],
"normalized": []
},
{
"id": "1219",
"type": "protein_domain_or_region",
"text": [
"NH2-"
],
"offsets": [
[
831,
835
]
],
"normalized": []
},
{
"id": "1220",
"type": "protein_domain_or_region",
"text": [
"COOH-terminal portion"
],
"offsets": [
[
847,
868
]
],
"normalized": []
},
{
"id": "1221",
"type": "other_name",
"text": [
"nm23 function"
],
"offsets": [
[
930,
943
]
],
"normalized": []
},
{
"id": "1222",
"type": "protein_molecule",
"text": [
"nm23"
],
"offsets": [
[
930,
934
]
],
"normalized": []
},
{
"id": "1223",
"type": "RNA_molecule",
"text": [
"DR-nm23 mRNA"
],
"offsets": [
[
945,
957
]
],
"normalized": []
},
{
"id": "1224",
"type": "protein_molecule",
"text": [
"DR-nm23"
],
"offsets": [
[
945,
952
]
],
"normalized": []
},
{
"id": "1225",
"type": "other_name",
"text": [
"myeloid differentiation"
],
"offsets": [
[
1005,
1028
]
],
"normalized": []
},
{
"id": "1226",
"type": "cell_line",
"text": [
"highly purified CD34+ cells"
],
"offsets": [
[
1032,
1059
]
],
"normalized": []
},
{
"id": "1227",
"type": "cell_line",
"text": [
"myeloid precursor 32Dc13 cell line"
],
"offsets": [
[
1096,
1130
]
],
"normalized": []
},
{
"id": "1228",
"type": "other_name",
"text": [
"growth-factor dependent"
],
"offsets": [
[
1141,
1164
]
],
"normalized": []
},
{
"id": "1229",
"type": "other_name",
"text": [
"proliferation"
],
"offsets": [
[
1174,
1187
]
],
"normalized": []
},
{
"id": "1230",
"type": "other_name",
"text": [
"differentiation"
],
"offsets": [
[
1192,
1207
]
],
"normalized": []
},
{
"id": "1231",
"type": "other_name",
"text": [
"granulocytic differentiation"
],
"offsets": [
[
1234,
1262
]
],
"normalized": []
},
{
"id": "1232",
"type": "other_name",
"text": [
"differentiation"
],
"offsets": [
[
1247,
1262
]
],
"normalized": []
},
{
"id": "1233",
"type": "protein_molecule",
"text": [
"granulocyte colony-stimulating factor"
],
"offsets": [
[
1274,
1311
]
],
"normalized": []
},
{
"id": "1234",
"type": "cell_type",
"text": [
"granulocyte"
],
"offsets": [
[
1274,
1285
]
],
"normalized": []
},
{
"id": "1235",
"type": "other_name",
"text": [
"apoptotic cell death"
],
"offsets": [
[
1323,
1343
]
],
"normalized": []
},
{
"id": "1236",
"type": "protein_molecule",
"text": [
"DR-nm23"
],
"offsets": [
[
1390,
1397
]
],
"normalized": []
},
{
"id": "1237",
"type": "other_name",
"text": [
"normal hematopoiesis"
],
"offsets": [
[
1401,
1421
]
],
"normalized": []
},
{
"id": "1238",
"type": "other_name",
"text": [
"overexpression"
],
"offsets": [
[
1457,
1471
]
],
"normalized": []
},
{
"id": "1239",
"type": "other_name",
"text": [
"differentiation arrest"
],
"offsets": [
[
1487,
1509
]
],
"normalized": []
},
{
"id": "1240",
"type": "other_name",
"text": [
"differentiation"
],
"offsets": [
[
1487,
1502
]
],
"normalized": []
},
{
"id": "1241",
"type": "other_name",
"text": [
"blastic transformation"
],
"offsets": [
[
1524,
1546
]
],
"normalized": []
},
{
"id": "1242",
"type": "other_name",
"text": [
"chronic myelogenous leukemia"
],
"offsets": [
[
1550,
1578
]
],
"normalized": []
}
] | [] | [] | [] |
1243 | 96032864 | [
{
"id": "1244",
"type": "title",
"text": [
"An interferon-gamma activation sequence mediates the transcriptional regulation of the IgG Fc receptor type IC gene by interferon-gamma."
],
"offsets": [
[
0,
136
]
]
},
{
"id": "1245",
"type": "abstract",
"text": [
"Expression of the IgG Fc receptor type I (Fc gamma RI) on myeloid cells is dramatically increased by treatment with interferon-gamma (IFN-gamma). We observed that Fc gamma RI transcript levels in monoblast-like U937 cells were elevated within 3 hr and peaked 12 hr after exposure to IFN-gamma. Treatment of U937 with IFN-gamma for 9 hr in the presence of cycloheximide led to super-induction of Fc gamma RI expression. Nuclear run-on analysis revealed that the rate of Fc gamma RI transcription was increased by IFN-gamma. Genomic sequence upstream of the Fc gamma RIC gene was cloned and subjected to primer extension analysis, which demonstrated a single transcription initiation site without a TATA box. Transient transfections of CAT reporter gene constructs containing various Fc gamma RIC promoter sequences into U937 cells revealed that a 20-bp region surrounding the transcription start site (-7 to +13) was capable of mediating transcription initiation and that an IFN-gamma responsive element (GIRE) was present within 74 bp upstream of the transcription initiation site. A 17-bp sequence between positions -51 and -35 conferred IFN-gamma responsiveness on a heterologous promoter. Double-stranded GIRE sequence, but not a scrambled sequence, was specifically bound by nuclear proteins from IFN-gamma treated U937 cells. Gel shift experiments further showed that the STAT1 alpha protein bound to the Fc gamma RIC GIRE in response to IFN-gamma treatment of U937 cells. The Fc gamma RIC GIRE is homologous to the IFN-gamma activation sequence (GAS) of the guanylate binding protein and to X box elements of class II MHC genes. Our results demonstrate that transcriptional regulation of the Fc gamma RIC gene by IFN-gamma involves the binding of STAT1 alpha to a 17-bp GAS homology in the proximal promoter."
],
"offsets": [
[
137,
1951
]
]
}
] | [
{
"id": "1246",
"type": "DNA_domain_or_region",
"text": [
"interferon-gamma activation sequence"
],
"offsets": [
[
3,
39
]
],
"normalized": []
},
{
"id": "1247",
"type": "other_name",
"text": [
"transcriptional regulation"
],
"offsets": [
[
53,
79
]
],
"normalized": []
},
{
"id": "1248",
"type": "DNA_domain_or_region",
"text": [
"IgG Fc receptor type IC gene"
],
"offsets": [
[
87,
115
]
],
"normalized": []
},
{
"id": "1249",
"type": "protein_family_or_group",
"text": [
"IgG Fc receptor"
],
"offsets": [
[
87,
102
]
],
"normalized": []
},
{
"id": "1250",
"type": "protein_molecule",
"text": [
"interferon-gamma"
],
"offsets": [
[
3,
19
]
],
"normalized": []
},
{
"id": "1251",
"type": "protein_molecule",
"text": [
"IgG Fc receptor type I"
],
"offsets": [
[
155,
177
]
],
"normalized": []
},
{
"id": "1252",
"type": "protein_family_or_group",
"text": [
"IgG Fc receptor"
],
"offsets": [
[
155,
170
]
],
"normalized": []
},
{
"id": "1253",
"type": "protein_molecule",
"text": [
"Fc gamma RI"
],
"offsets": [
[
179,
190
]
],
"normalized": []
},
{
"id": "1254",
"type": "cell_type",
"text": [
"myeloid cells"
],
"offsets": [
[
195,
208
]
],
"normalized": []
},
{
"id": "1255",
"type": "protein_molecule",
"text": [
"interferon-gamma"
],
"offsets": [
[
253,
269
]
],
"normalized": []
},
{
"id": "1256",
"type": "protein_molecule",
"text": [
"IFN-gamma"
],
"offsets": [
[
271,
280
]
],
"normalized": []
},
{
"id": "1257",
"type": "other_name",
"text": [
"Fc gamma RI transcript levels"
],
"offsets": [
[
300,
329
]
],
"normalized": []
},
{
"id": "1258",
"type": "protein_molecule",
"text": [
"Fc gamma RI"
],
"offsets": [
[
300,
311
]
],
"normalized": []
},
{
"id": "1259",
"type": "cell_line",
"text": [
"monoblast-like U937 cells"
],
"offsets": [
[
333,
358
]
],
"normalized": []
},
{
"id": "1260",
"type": "protein_molecule",
"text": [
"IFN-gamma"
],
"offsets": [
[
420,
429
]
],
"normalized": []
},
{
"id": "1261",
"type": "cell_line",
"text": [
"U937"
],
"offsets": [
[
444,
448
]
],
"normalized": []
},
{
"id": "1262",
"type": "protein_molecule",
"text": [
"IFN-gamma"
],
"offsets": [
[
454,
463
]
],
"normalized": []
},
{
"id": "1263",
"type": "protein_molecule",
"text": [
"Fc gamma RI"
],
"offsets": [
[
532,
543
]
],
"normalized": []
},
{
"id": "1264",
"type": "protein_molecule",
"text": [
"Fc gamma RI"
],
"offsets": [
[
606,
617
]
],
"normalized": []
},
{
"id": "1265",
"type": "protein_molecule",
"text": [
"IFN-gamma"
],
"offsets": [
[
649,
658
]
],
"normalized": []
},
{
"id": "1266",
"type": "DNA_domain_or_region",
"text": [
"Fc gamma RIC gene"
],
"offsets": [
[
693,
710
]
],
"normalized": []
},
{
"id": "1267",
"type": "other_name",
"text": [
"primer extension analysis"
],
"offsets": [
[
739,
764
]
],
"normalized": []
},
{
"id": "1268",
"type": "DNA_domain_or_region",
"text": [
"transcription initiation site"
],
"offsets": [
[
794,
823
]
],
"normalized": []
},
{
"id": "1269",
"type": "DNA_domain_or_region",
"text": [
"TATA box"
],
"offsets": [
[
834,
842
]
],
"normalized": []
},
{
"id": "1270",
"type": "DNA_family_or_group",
"text": [
"CAT reporter gene constructs"
],
"offsets": [
[
871,
899
]
],
"normalized": []
},
{
"id": "1271",
"type": "DNA_family_or_group",
"text": [
"reporter gene constructs"
],
"offsets": [
[
875,
899
]
],
"normalized": []
},
{
"id": "1272",
"type": "DNA_domain_or_region",
"text": [
"Fc gamma RIC promoter sequences"
],
"offsets": [
[
919,
950
]
],
"normalized": []
},
{
"id": "1273",
"type": "cell_line",
"text": [
"U937 cells"
],
"offsets": [
[
956,
966
]
],
"normalized": []
},
{
"id": "1274",
"type": "DNA_domain_or_region",
"text": [
"20-bp region"
],
"offsets": [
[
983,
995
]
],
"normalized": []
},
{
"id": "1275",
"type": "DNA_domain_or_region",
"text": [
"transcription start site"
],
"offsets": [
[
1012,
1036
]
],
"normalized": []
},
{
"id": "1276",
"type": "other_name",
"text": [
"transcription initiation"
],
"offsets": [
[
1074,
1098
]
],
"normalized": []
},
{
"id": "1277",
"type": "DNA_domain_or_region",
"text": [
"IFN-gamma responsive element"
],
"offsets": [
[
1111,
1139
]
],
"normalized": []
},
{
"id": "1278",
"type": "DNA_domain_or_region",
"text": [
"GIRE"
],
"offsets": [
[
1141,
1145
]
],
"normalized": []
},
{
"id": "1279",
"type": "DNA_domain_or_region",
"text": [
"74 bp upstream"
],
"offsets": [
[
1166,
1180
]
],
"normalized": []
},
{
"id": "1280",
"type": "DNA_domain_or_region",
"text": [
"transcription initiation site"
],
"offsets": [
[
1188,
1217
]
],
"normalized": []
},
{
"id": "1281",
"type": "other_name",
"text": [
"transcription initiation"
],
"offsets": [
[
1188,
1212
]
],
"normalized": []
},
{
"id": "1282",
"type": "DNA_domain_or_region",
"text": [
"17-bp sequence"
],
"offsets": [
[
1221,
1235
]
],
"normalized": []
},
{
"id": "1283",
"type": "other_name",
"text": [
"IFN-gamma responsiveness"
],
"offsets": [
[
1276,
1300
]
],
"normalized": []
},
{
"id": "1284",
"type": "protein_molecule",
"text": [
"IFN-gamma"
],
"offsets": [
[
1276,
1285
]
],
"normalized": []
},
{
"id": "1285",
"type": "DNA_domain_or_region",
"text": [
"heterologous promoter"
],
"offsets": [
[
1306,
1327
]
],
"normalized": []
},
{
"id": "1286",
"type": "DNA_domain_or_region",
"text": [
"Double-stranded GIRE sequence"
],
"offsets": [
[
1329,
1358
]
],
"normalized": []
},
{
"id": "1287",
"type": "DNA_family_or_group",
"text": [
"scrambled sequence"
],
"offsets": [
[
1370,
1388
]
],
"normalized": []
},
{
"id": "1288",
"type": "protein_family_or_group",
"text": [
"nuclear proteins"
],
"offsets": [
[
1416,
1432
]
],
"normalized": []
},
{
"id": "1289",
"type": "cell_line",
"text": [
"IFN-gamma treated U937 cells"
],
"offsets": [
[
1438,
1466
]
],
"normalized": []
},
{
"id": "1290",
"type": "protein_molecule",
"text": [
"IFN-gamma"
],
"offsets": [
[
1438,
1447
]
],
"normalized": []
},
{
"id": "1291",
"type": "cell_line",
"text": [
"U937 cells"
],
"offsets": [
[
1456,
1466
]
],
"normalized": []
},
{
"id": "1292",
"type": "protein_molecule",
"text": [
"STAT1 alpha protein"
],
"offsets": [
[
1514,
1533
]
],
"normalized": []
},
{
"id": "1293",
"type": "DNA_domain_or_region",
"text": [
"Fc gamma RIC GIRE"
],
"offsets": [
[
1547,
1564
]
],
"normalized": []
},
{
"id": "1294",
"type": "other_name",
"text": [
"IFN-gamma treatment"
],
"offsets": [
[
1580,
1599
]
],
"normalized": []
},
{
"id": "1295",
"type": "protein_molecule",
"text": [
"IFN-gamma"
],
"offsets": [
[
1580,
1589
]
],
"normalized": []
},
{
"id": "1296",
"type": "cell_line",
"text": [
"U937 cells"
],
"offsets": [
[
1603,
1613
]
],
"normalized": []
},
{
"id": "1297",
"type": "DNA_domain_or_region",
"text": [
"Fc gamma RIC GIRE"
],
"offsets": [
[
1619,
1636
]
],
"normalized": []
},
{
"id": "1298",
"type": "DNA_domain_or_region",
"text": [
"IFN-gamma activation sequence"
],
"offsets": [
[
1658,
1687
]
],
"normalized": []
},
{
"id": "1299",
"type": "protein_molecule",
"text": [
"IFN-gamma"
],
"offsets": [
[
1658,
1667
]
],
"normalized": []
},
{
"id": "1300",
"type": "DNA_domain_or_region",
"text": [
"GAS"
],
"offsets": [
[
1689,
1692
]
],
"normalized": []
},
{
"id": "1301",
"type": "protein_molecule",
"text": [
"guanylate binding protein"
],
"offsets": [
[
1701,
1726
]
],
"normalized": []
},
{
"id": "1302",
"type": "DNA_family_or_group",
"text": [
"X box elements"
],
"offsets": [
[
1734,
1748
]
],
"normalized": []
},
{
"id": "1303",
"type": "DNA_family_or_group",
"text": [
"class II MHC genes"
],
"offsets": [
[
1752,
1770
]
],
"normalized": []
},
{
"id": "1304",
"type": "other_name",
"text": [
"transcriptional regulation"
],
"offsets": [
[
1801,
1827
]
],
"normalized": []
},
{
"id": "1305",
"type": "DNA_domain_or_region",
"text": [
"Fc gamma RIC gene"
],
"offsets": [
[
1835,
1852
]
],
"normalized": []
},
{
"id": "1306",
"type": "protein_molecule",
"text": [
"IFN-gamma"
],
"offsets": [
[
1856,
1865
]
],
"normalized": []
},
{
"id": "1307",
"type": "protein_molecule",
"text": [
"STAT1 alpha"
],
"offsets": [
[
1890,
1901
]
],
"normalized": []
},
{
"id": "1308",
"type": "DNA_domain_or_region",
"text": [
"17-bp GAS homology"
],
"offsets": [
[
1907,
1925
]
],
"normalized": []
},
{
"id": "1309",
"type": "DNA_domain_or_region",
"text": [
"proximal promoter"
],
"offsets": [
[
1933,
1950
]
],
"normalized": []
}
] | [] | [] | [] |
1310 | 95327953 | [
{
"id": "1311",
"type": "title",
"text": [
"Constitutively activated Jak-STAT pathway in T cells transformed with HTLV-I."
],
"offsets": [
[
0,
77
]
]
},
{
"id": "1312",
"type": "abstract",
"text": [
"Human T cell lymphotropic virus I (HTLV-I) is the etiological agent for adult T cell leukemia and tropical spastic paraparesis (also termed HTLV-I-associated myelopathy). HTLV-I-infected peripheral blood T cells exhibit an initial phase of interleukin-2 (IL-2)-dependent growth; over time, by an unknown mechanism, the cells become IL-2-independent. Whereas the Jak kinases Jak1 and Jak3 and the signal transducer and activator of transcription proteins Stat3 and Stat5 are activated in normal T cells in response to IL-2, this signaling pathway was constitutively activated in HTLV-I-transformed cells. In HTLV-I-infected cord blood lymphocytes, the transition from IL-2-dependent to IL-2-independent growth correlated with the acquisition of a constitutively activated Jak-STAT pathway, which suggests that this pathway participates in HTLV-I-mediated T cell transformation."
],
"offsets": [
[
78,
954
]
]
}
] | [
{
"id": "1313",
"type": "other_name",
"text": [
"Jak-STAT pathway"
],
"offsets": [
[
25,
41
]
],
"normalized": []
},
{
"id": "1314",
"type": "protein_family_or_group",
"text": [
"Jak"
],
"offsets": [
[
25,
28
]
],
"normalized": []
},
{
"id": "1315",
"type": "protein_family_or_group",
"text": [
"-STAT"
],
"offsets": [
[
28,
33
]
],
"normalized": []
},
{
"id": "1316",
"type": "cell_type",
"text": [
"T cells"
],
"offsets": [
[
45,
52
]
],
"normalized": []
},
{
"id": "1317",
"type": "virus",
"text": [
"HTLV-I"
],
"offsets": [
[
70,
76
]
],
"normalized": []
},
{
"id": "1318",
"type": "virus",
"text": [
"Human T cell lymphotropic virus I"
],
"offsets": [
[
78,
111
]
],
"normalized": []
},
{
"id": "1319",
"type": "virus",
"text": [
"HTLV-I"
],
"offsets": [
[
113,
119
]
],
"normalized": []
},
{
"id": "1320",
"type": "other_name",
"text": [
"etiological agent"
],
"offsets": [
[
128,
145
]
],
"normalized": []
},
{
"id": "1321",
"type": "other_name",
"text": [
"adult T cell leukemia"
],
"offsets": [
[
150,
171
]
],
"normalized": []
},
{
"id": "1322",
"type": "other_name",
"text": [
"tropical spastic paraparesis"
],
"offsets": [
[
176,
204
]
],
"normalized": []
},
{
"id": "1323",
"type": "other_name",
"text": [
"HTLV-I-associated myelopathy"
],
"offsets": [
[
218,
246
]
],
"normalized": []
},
{
"id": "1324",
"type": "virus",
"text": [
"HTLV-I"
],
"offsets": [
[
218,
224
]
],
"normalized": []
},
{
"id": "1325",
"type": "cell_type",
"text": [
"HTLV-I-infected peripheral blood T cells"
],
"offsets": [
[
249,
289
]
],
"normalized": []
},
{
"id": "1326",
"type": "virus",
"text": [
"HTLV-I"
],
"offsets": [
[
249,
255
]
],
"normalized": []
},
{
"id": "1327",
"type": "cell_type",
"text": [
"T cells"
],
"offsets": [
[
282,
289
]
],
"normalized": []
},
{
"id": "1328",
"type": "other_name",
"text": [
"interleukin-2 (IL-2)-dependent growth"
],
"offsets": [
[
318,
355
]
],
"normalized": []
},
{
"id": "1329",
"type": "protein_molecule",
"text": [
"interleukin-2"
],
"offsets": [
[
318,
331
]
],
"normalized": []
},
{
"id": "1330",
"type": "protein_molecule",
"text": [
"IL-2"
],
"offsets": [
[
333,
337
]
],
"normalized": []
},
{
"id": "1331",
"type": "other_name",
"text": [
"IL-2-independent"
],
"offsets": [
[
410,
426
]
],
"normalized": []
},
{
"id": "1332",
"type": "protein_molecule",
"text": [
"IL-2"
],
"offsets": [
[
410,
414
]
],
"normalized": []
},
{
"id": "1333",
"type": "protein_family_or_group",
"text": [
"Jak kinases"
],
"offsets": [
[
440,
451
]
],
"normalized": []
},
{
"id": "1334",
"type": "protein_molecule",
"text": [
"Jak1"
],
"offsets": [
[
452,
456
]
],
"normalized": []
},
{
"id": "1335",
"type": "protein_molecule",
"text": [
"Jak3"
],
"offsets": [
[
461,
465
]
],
"normalized": []
},
{
"id": "1336",
"type": "protein_family_or_group",
"text": [
"transcription proteins"
],
"offsets": [
[
509,
531
]
],
"normalized": []
},
{
"id": "1337",
"type": "protein_molecule",
"text": [
"Stat3"
],
"offsets": [
[
532,
537
]
],
"normalized": []
},
{
"id": "1338",
"type": "protein_molecule",
"text": [
"Stat5"
],
"offsets": [
[
542,
547
]
],
"normalized": []
},
{
"id": "1339",
"type": "cell_type",
"text": [
"normal T cells"
],
"offsets": [
[
565,
579
]
],
"normalized": []
},
{
"id": "1340",
"type": "cell_type",
"text": [
"T cells"
],
"offsets": [
[
572,
579
]
],
"normalized": []
},
{
"id": "1341",
"type": "protein_molecule",
"text": [
"IL-2"
],
"offsets": [
[
595,
599
]
],
"normalized": []
},
{
"id": "1342",
"type": "cell_line",
"text": [
"HTLV-I-transformed cells"
],
"offsets": [
[
656,
680
]
],
"normalized": []
},
{
"id": "1343",
"type": "virus",
"text": [
"HTLV-I"
],
"offsets": [
[
656,
662
]
],
"normalized": []
},
{
"id": "1344",
"type": "cell_line",
"text": [
"HTLV-I-infected cord blood lymphocytes"
],
"offsets": [
[
685,
723
]
],
"normalized": []
},
{
"id": "1345",
"type": "virus",
"text": [
"HTLV-I"
],
"offsets": [
[
685,
691
]
],
"normalized": []
},
{
"id": "1346",
"type": "other_name",
"text": [
"IL-2-dependent"
],
"offsets": [
[
745,
759
]
],
"normalized": []
},
{
"id": "1347",
"type": "protein_molecule",
"text": [
"IL-2"
],
"offsets": [
[
745,
749
]
],
"normalized": []
},
{
"id": "1348",
"type": "other_name",
"text": [
"IL-2-independent growth"
],
"offsets": [
[
763,
786
]
],
"normalized": []
},
{
"id": "1349",
"type": "protein_molecule",
"text": [
"IL-2"
],
"offsets": [
[
763,
767
]
],
"normalized": []
},
{
"id": "1350",
"type": "other_name",
"text": [
"Jak-STAT pathway"
],
"offsets": [
[
849,
865
]
],
"normalized": []
},
{
"id": "1351",
"type": "protein_family_or_group",
"text": [
"Jak"
],
"offsets": [
[
849,
852
]
],
"normalized": []
},
{
"id": "1352",
"type": "protein_family_or_group",
"text": [
"-STAT"
],
"offsets": [
[
852,
857
]
],
"normalized": []
},
{
"id": "1353",
"type": "other_name",
"text": [
"HTLV-I-mediated T cell transformation"
],
"offsets": [
[
916,
953
]
],
"normalized": []
},
{
"id": "1354",
"type": "virus",
"text": [
"HTLV-I"
],
"offsets": [
[
916,
922
]
],
"normalized": []
}
] | [] | [] | [] |
1355 | 95340873 | [
{
"id": "1356",
"type": "title",
"text": [
"Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines."
],
"offsets": [
[
0,
172
]
]
},
{
"id": "1357",
"type": "abstract",
"text": [
"To test the hypothesis that nitric oxide (NO) limits endothelial activation, we treated cytokine-stimulated human saphenous vein endothelial cells with several NO donors and assessed their effects on the inducible expression of vascular cell adhesion molecule-1 (VCAM-1). In a concentration-dependent manner, NO inhibited interleukin (IL)-1 alpha-stimulated VCAM-1 expression by 35-55% as determined by cell surface enzyme immunoassays and flow cytometry. This inhibition was paralleled by reduced monocyte adhesion to endothelial monolayers in nonstatic assays, was unaffected by cGMP analogues, and was quantitatively similar after stimulation by either IL-1 alpha, IL-1 beta, IL-4, tumor necrosis factor (TNF alpha), or bacterial lipopolysaccharide. NO also decreased the endothelial expression of other leukocyte adhesion molecules (E-selectin and to a lesser extent, intercellular adhesion molecule-1) and secretable cytokines (IL-6 and IL-8). Inhibition of endogenous NO production by L-N-monomethyl-arginine also induced the expression of VCAM-1, but did not augment cytokine-induced VCAM-1 expression. Nuclear run-on assays, transfection studies using various VCAM-1 promoter reporter gene constructs, and electrophoretic mobility shift assays indicated that NO represses VCAM-1 gene transcription, in part, by inhibiting NF-kappa B. We propose that NO's ability to limit endothelial activation and inhibit monocyte adhesion may contribute to some of its antiatherogenic and antiinflammatory properties within the vessel wall."
],
"offsets": [
[
173,
1707
]
]
}
] | [
{
"id": "1358",
"type": "inorganic",
"text": [
"Nitric oxide"
],
"offsets": [
[
0,
12
]
],
"normalized": []
},
{
"id": "1359",
"type": "other_name",
"text": [
"cytokine-induced endothelial activation"
],
"offsets": [
[
23,
62
]
],
"normalized": []
},
{
"id": "1360",
"type": "protein_family_or_group",
"text": [
"cytokine"
],
"offsets": [
[
23,
31
]
],
"normalized": []
},
{
"id": "1361",
"type": "inorganic",
"text": [
"Nitric oxide"
],
"offsets": [
[
64,
76
]
],
"normalized": []
},
{
"id": "1362",
"type": "other_name",
"text": [
"endothelial expression"
],
"offsets": [
[
97,
119
]
],
"normalized": []
},
{
"id": "1363",
"type": "protein_family_or_group",
"text": [
"adhesion molecules"
],
"offsets": [
[
123,
141
]
],
"normalized": []
},
{
"id": "1364",
"type": "protein_family_or_group",
"text": [
"proinflammatory cytokines"
],
"offsets": [
[
146,
171
]
],
"normalized": []
},
{
"id": "1365",
"type": "inorganic",
"text": [
"nitric oxide"
],
"offsets": [
[
201,
213
]
],
"normalized": []
},
{
"id": "1366",
"type": "inorganic",
"text": [
"NO"
],
"offsets": [
[
215,
217
]
],
"normalized": []
},
{
"id": "1367",
"type": "other_name",
"text": [
"endothelial activation"
],
"offsets": [
[
226,
248
]
],
"normalized": []
},
{
"id": "1368",
"type": "cell_line",
"text": [
"cytokine-stimulated human saphenous vein endothelial cells"
],
"offsets": [
[
261,
319
]
],
"normalized": []
},
{
"id": "1369",
"type": "inorganic",
"text": [
"NO donors"
],
"offsets": [
[
333,
342
]
],
"normalized": []
},
{
"id": "1370",
"type": "inorganic",
"text": [
"NO"
],
"offsets": [
[
333,
335
]
],
"normalized": []
},
{
"id": "1371",
"type": "protein_molecule",
"text": [
"vascular cell adhesion molecule-1"
],
"offsets": [
[
401,
434
]
],
"normalized": []
},
{
"id": "1372",
"type": "protein_molecule",
"text": [
"VCAM-1"
],
"offsets": [
[
436,
442
]
],
"normalized": []
},
{
"id": "1373",
"type": "other_name",
"text": [
"concentration-dependent manner"
],
"offsets": [
[
450,
480
]
],
"normalized": []
},
{
"id": "1374",
"type": "inorganic",
"text": [
"NO"
],
"offsets": [
[
482,
484
]
],
"normalized": []
},
{
"id": "1375",
"type": "other_name",
"text": [
"interleukin (IL)-1 alpha-stimulated VCAM-1 expression"
],
"offsets": [
[
495,
548
]
],
"normalized": []
},
{
"id": "1376",
"type": "protein_molecule",
"text": [
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],
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[
495,
513
]
],
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},
{
"id": "1377",
"type": "protein_molecule",
"text": [
"VCAM-1"
],
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[
531,
537
]
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},
{
"id": "1378",
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"offsets": [
[
576,
608
]
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{
"id": "1379",
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"text": [
"flow cytometry"
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613,
627
]
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},
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671,
688
]
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},
{
"id": "1381",
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"text": [
"endothelial monolayers"
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692,
714
]
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},
{
"id": "1382",
"type": "other_name",
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"nonstatic assays"
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[
718,
734
]
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},
{
"id": "1383",
"type": "other_organic_compound",
"text": [
"cGMP analogues"
],
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[
754,
768
]
],
"normalized": []
},
{
"id": "1384",
"type": "protein_family_or_group",
"text": [
"IL-1 alpha"
],
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829,
839
]
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{
"id": "1385",
"type": "protein_molecule",
"text": [
"IL-1 beta"
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[
841,
850
]
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{
"id": "1386",
"type": "protein_molecule",
"text": [
"IL-4"
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[
852,
856
]
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},
{
"id": "1387",
"type": "protein_family_or_group",
"text": [
"tumor necrosis factor"
],
"offsets": [
[
858,
879
]
],
"normalized": []
},
{
"id": "1388",
"type": "protein_molecule",
"text": [
"TNF alpha"
],
"offsets": [
[
881,
890
]
],
"normalized": []
},
{
"id": "1389",
"type": "lipid",
"text": [
"bacterial lipopolysaccharide"
],
"offsets": [
[
896,
924
]
],
"normalized": []
},
{
"id": "1390",
"type": "inorganic",
"text": [
"NO"
],
"offsets": [
[
926,
928
]
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"normalized": []
},
{
"id": "1391",
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],
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948,
970
]
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{
"id": "1392",
"type": "protein_family_or_group",
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],
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980,
1008
]
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"id": "1393",
"type": "protein_family_or_group",
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990,
1008
]
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"id": "1394",
"type": "protein_molecule",
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1010,
1020
]
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{
"id": "1395",
"type": "protein_molecule",
"text": [
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1045,
1078
]
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},
{
"id": "1396",
"type": "protein_family_or_group",
"text": [
"cytokines"
],
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1095,
1104
]
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},
{
"id": "1397",
"type": "protein_molecule",
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"IL-6"
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1106,
1110
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{
"id": "1398",
"type": "protein_molecule",
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"IL-8"
],
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1115,
1119
]
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},
{
"id": "1399",
"type": "inorganic",
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"NO"
],
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1147,
1149
]
],
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},
{
"id": "1400",
"type": "amino_acid_monomer",
"text": [
"L-N-monomethyl-arginine"
],
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[
1164,
1187
]
],
"normalized": []
},
{
"id": "1401",
"type": "protein_molecule",
"text": [
"VCAM-1"
],
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[
1219,
1225
]
],
"normalized": []
},
{
"id": "1402",
"type": "other_name",
"text": [
"cytokine-induced VCAM-1 expression"
],
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[
1247,
1281
]
],
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},
{
"id": "1403",
"type": "protein_molecule",
"text": [
"VCAM-1"
],
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[
1264,
1270
]
],
"normalized": []
},
{
"id": "1404",
"type": "other_name",
"text": [
"Nuclear run-on assays"
],
"offsets": [
[
1283,
1304
]
],
"normalized": []
},
{
"id": "1405",
"type": "other_name",
"text": [
"transfection studies"
],
"offsets": [
[
1306,
1326
]
],
"normalized": []
},
{
"id": "1406",
"type": "DNA_domain_or_region",
"text": [
"VCAM-1 promoter reporter gene constructs"
],
"offsets": [
[
1341,
1381
]
],
"normalized": []
},
{
"id": "1407",
"type": "protein_molecule",
"text": [
"VCAM-1"
],
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[
1341,
1347
]
],
"normalized": []
},
{
"id": "1408",
"type": "DNA_family_or_group",
"text": [
"reporter gene constructs"
],
"offsets": [
[
1357,
1381
]
],
"normalized": []
},
{
"id": "1409",
"type": "other_name",
"text": [
"electrophoretic mobility shift assays"
],
"offsets": [
[
1387,
1424
]
],
"normalized": []
},
{
"id": "1410",
"type": "inorganic",
"text": [
"NO"
],
"offsets": [
[
1440,
1442
]
],
"normalized": []
},
{
"id": "1411",
"type": "other_name",
"text": [
"VCAM-1 gene transcription"
],
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[
1453,
1478
]
],
"normalized": []
},
{
"id": "1412",
"type": "protein_molecule",
"text": [
"VCAM-1"
],
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[
1453,
1459
]
],
"normalized": []
},
{
"id": "1413",
"type": "protein_molecule",
"text": [
"NF-kappa B"
],
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[
1503,
1513
]
],
"normalized": []
},
{
"id": "1414",
"type": "inorganic",
"text": [
"NO"
],
"offsets": [
[
1531,
1533
]
],
"normalized": []
},
{
"id": "1415",
"type": "other_name",
"text": [
"endothelial activation"
],
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[
1553,
1575
]
],
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},
{
"id": "1416",
"type": "other_name",
"text": [
"monocyte adhesion"
],
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[
1588,
1605
]
],
"normalized": []
},
{
"id": "1417",
"type": "(AND other_name other_name)",
"text": [
"antiatherogenic and antiinflammatory properties"
],
"offsets": [
[
1636,
1683
]
],
"normalized": []
},
{
"id": "1418",
"type": "",
"text": [
"antiatherogenic"
],
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1636,
1651
]
],
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},
{
"id": "1419",
"type": "",
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"antiinflammatory"
],
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[
1656,
1672
]
],
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},
{
"id": "1420",
"type": "",
"text": [
"properties"
],
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[
1673,
1683
]
],
"normalized": []
},
{
"id": "1421",
"type": "tissue",
"text": [
"vessel wall"
],
"offsets": [
[
1695,
1706
]
],
"normalized": []
}
] | [] | [] | [] |
1422 | 95280909 | [
{
"id": "1423",
"type": "title",
"text": [
"MIP1 alpha nuclear protein (MNP), a novel transcription factor expressed in hematopoietic cells that is crucial for transcription of the human MIP-1 alpha gene."
],
"offsets": [
[
0,
160
]
]
},
{
"id": "1424",
"type": "abstract",
"text": [
"Murine macrophage inflammatory protein 1 alpha (MIP-1 alpha) and its human equivalent (GOS19, LD78, or AT464) are members of the -C-C family of low-molecular-weight chemokines. Secreted from activated T cells and macrophages, bone marrow-derived MIP-1 alpha/GOS19 inhibits primitive hematopoietic stem cells and appears to be involved in the homeostatic control of stem cell proliferation. It also induces chemotaxis and inflammatory responses in mature cell types. Therefore, it is important to understand the mechanisms which control the expression of MIP-1 alpha/GOS19. Previous work has shown that in Jurkat T cells, a set of widely expressed transcription factors (the ICK-1 family) affect the GOS19 promoter. One member, ICK-1A, behaves as a strong negative regulator. In this communication, we provide evidence that the pathway of induction in the macrophage cell line U937 is different from that in Jurkat cells. Furthermore, we show that the ICK-1 binding site does not confer negative regulation in U937 cells. We provide evidence for an additional binding site, the MIP-1 alpha nuclear protein (MNP) site, which overlaps the ICK-1 site. Interaction of nuclear extracts from various cell lines and tissue with the MNP site leads to the formation of fast-migrating protein-DNA complexes with similar but distinct electrophoretic mobilities. A mutation of the MNP site which does not abrogate ICK-1 binding inactivates the GOS19.1 promoter in U937 cells and reduces its activity by fourfold in Jurkat cells. We propose that the MNP protein(s) binding at the MNP site constitutes a novel transcription factor(s) expressed in hematopoietic cells."
],
"offsets": [
[
161,
1813
]
]
}
] | [
{
"id": "1425",
"type": "protein_molecule",
"text": [
"MIP1 alpha nuclear protein"
],
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[
0,
26
]
],
"normalized": []
},
{
"id": "1426",
"type": "protein_molecule",
"text": [
"MNP"
],
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28,
31
]
],
"normalized": []
},
{
"id": "1427",
"type": "protein_family_or_group",
"text": [
"transcription factor"
],
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[
42,
62
]
],
"normalized": []
},
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"id": "1428",
"type": "other_name",
"text": [
"transcription"
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[
42,
55
]
],
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},
{
"id": "1429",
"type": "DNA_domain_or_region",
"text": [
"human MIP-1 alpha gene"
],
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[
137,
159
]
],
"normalized": []
},
{
"id": "1430",
"type": "protein_molecule",
"text": [
"Murine macrophage inflammatory protein 1 alpha"
],
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[
161,
207
]
],
"normalized": []
},
{
"id": "1431",
"type": "protein_molecule",
"text": [
"MIP-1 alpha"
],
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[
209,
220
]
],
"normalized": []
},
{
"id": "1432",
"type": "protein_family_or_group",
"text": [
"human equivalent"
],
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[
230,
246
]
],
"normalized": []
},
{
"id": "1433",
"type": "protein_molecule",
"text": [
"GOS19"
],
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[
248,
253
]
],
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},
{
"id": "1434",
"type": "protein_molecule",
"text": [
"LD78"
],
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[
255,
259
]
],
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},
{
"id": "1435",
"type": "protein_molecule",
"text": [
"AT464"
],
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[
264,
269
]
],
"normalized": []
},
{
"id": "1436",
"type": "protein_family_or_group",
"text": [
"-C-C family"
],
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[
290,
301
]
],
"normalized": []
},
{
"id": "1437",
"type": "protein_domain_or_region",
"text": [
"low-molecular-weight chemokines"
],
"offsets": [
[
305,
336
]
],
"normalized": []
},
{
"id": "1438",
"type": "cell_type",
"text": [
"activated T cells"
],
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[
352,
369
]
],
"normalized": []
},
{
"id": "1439",
"type": "cell_type",
"text": [
"T cells"
],
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[
362,
369
]
],
"normalized": []
},
{
"id": "1440",
"type": "cell_type",
"text": [
"macrophages"
],
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[
374,
385
]
],
"normalized": []
},
{
"id": "1441",
"type": "protein_molecule",
"text": [
"marrow-derived MIP-1 alpha/GOS19"
],
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[
392,
424
]
],
"normalized": []
},
{
"id": "1442",
"type": "protein_molecule",
"text": [
"MIP-1 alpha"
],
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[
407,
418
]
],
"normalized": []
},
{
"id": "1443",
"type": "protein_molecule",
"text": [
"/GOS19"
],
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[
418,
424
]
],
"normalized": []
},
{
"id": "1444",
"type": "cell_type",
"text": [
"primitive hematopoietic stem cells"
],
"offsets": [
[
434,
468
]
],
"normalized": []
},
{
"id": "1445",
"type": "other_name",
"text": [
"stem cell proliferation"
],
"offsets": [
[
526,
549
]
],
"normalized": []
},
{
"id": "1446",
"type": "cell_type",
"text": [
"stem cell"
],
"offsets": [
[
458,
467
]
],
"normalized": []
},
{
"id": "1447",
"type": "other_name",
"text": [
"proliferation"
],
"offsets": [
[
536,
549
]
],
"normalized": []
},
{
"id": "1448",
"type": "other_name",
"text": [
"chemotaxis"
],
"offsets": [
[
567,
577
]
],
"normalized": []
},
{
"id": "1449",
"type": "other_name",
"text": [
"inflammatory responses"
],
"offsets": [
[
582,
604
]
],
"normalized": []
},
{
"id": "1450",
"type": "cell_type",
"text": [
"mature cell types"
],
"offsets": [
[
608,
625
]
],
"normalized": []
},
{
"id": "1451",
"type": "protein_molecule",
"text": [
"MIP-1 alpha"
],
"offsets": [
[
715,
726
]
],
"normalized": []
},
{
"id": "1452",
"type": "protein_molecule",
"text": [
"/GOS19"
],
"offsets": [
[
726,
732
]
],
"normalized": []
},
{
"id": "1453",
"type": "cell_line",
"text": [
"Jurkat T cells"
],
"offsets": [
[
766,
780
]
],
"normalized": []
},
{
"id": "1454",
"type": "cell_type",
"text": [
"T cells"
],
"offsets": [
[
773,
780
]
],
"normalized": []
},
{
"id": "1455",
"type": "protein_family_or_group",
"text": [
"transcription factors"
],
"offsets": [
[
808,
829
]
],
"normalized": []
},
{
"id": "1456",
"type": "protein_domain_or_region",
"text": [
"ICK-1 family"
],
"offsets": [
[
835,
847
]
],
"normalized": []
},
{
"id": "1457",
"type": "DNA_domain_or_region",
"text": [
"GOS19 promoter"
],
"offsets": [
[
860,
874
]
],
"normalized": []
},
{
"id": "1458",
"type": "protein_molecule",
"text": [
"GOS19"
],
"offsets": [
[
860,
865
]
],
"normalized": []
},
{
"id": "1459",
"type": "protein_molecule",
"text": [
"ICK-1A"
],
"offsets": [
[
888,
894
]
],
"normalized": []
},
{
"id": "1460",
"type": "protein_family_or_group",
"text": [
"strong negative regulator"
],
"offsets": [
[
909,
934
]
],
"normalized": []
},
{
"id": "1461",
"type": "cell_line",
"text": [
"macrophage cell line"
],
"offsets": [
[
1016,
1036
]
],
"normalized": []
},
{
"id": "1462",
"type": "cell_line",
"text": [
"U937"
],
"offsets": [
[
1037,
1041
]
],
"normalized": []
},
{
"id": "1463",
"type": "cell_line",
"text": [
"Jurkat cells"
],
"offsets": [
[
1068,
1080
]
],
"normalized": []
},
{
"id": "1464",
"type": "DNA_domain_or_region",
"text": [
"ICK-1 binding site"
],
"offsets": [
[
1112,
1130
]
],
"normalized": []
},
{
"id": "1465",
"type": "other_name",
"text": [
"negative regulation"
],
"offsets": [
[
1147,
1166
]
],
"normalized": []
},
{
"id": "1466",
"type": "cell_line",
"text": [
"U937 cells"
],
"offsets": [
[
1170,
1180
]
],
"normalized": []
},
{
"id": "1467",
"type": "DNA_domain_or_region",
"text": [
"binding site"
],
"offsets": [
[
1220,
1232
]
],
"normalized": []
},
{
"id": "1468",
"type": "DNA_domain_or_region",
"text": [
"MIP-1 alpha nuclear protein (MNP) site"
],
"offsets": [
[
1238,
1276
]
],
"normalized": []
},
{
"id": "1469",
"type": "protein_molecule",
"text": [
"MIP-1 alpha"
],
"offsets": [
[
1238,
1249
]
],
"normalized": []
},
{
"id": "1470",
"type": "DNA_domain_or_region",
"text": [
"ICK-1 site"
],
"offsets": [
[
1297,
1307
]
],
"normalized": []
},
{
"id": "1471",
"type": "cell_component",
"text": [
"nuclear extracts"
],
"offsets": [
[
1324,
1340
]
],
"normalized": []
},
{
"id": "1472",
"type": "cell_line",
"text": [
"various cell lines"
],
"offsets": [
[
1346,
1364
]
],
"normalized": []
},
{
"id": "1473",
"type": "tissue",
"text": [
"tissue"
],
"offsets": [
[
1369,
1375
]
],
"normalized": []
},
{
"id": "1474",
"type": "DNA_domain_or_region",
"text": [
"MNP site"
],
"offsets": [
[
1385,
1393
]
],
"normalized": []
},
{
"id": "1475",
"type": "protein_complex",
"text": [
"fast-migrating protein-DNA complexes"
],
"offsets": [
[
1420,
1456
]
],
"normalized": []
},
{
"id": "1476",
"type": "other_name",
"text": [
"electrophoretic mobilities"
],
"offsets": [
[
1483,
1509
]
],
"normalized": []
},
{
"id": "1477",
"type": "DNA_domain_or_region",
"text": [
"MNP site"
],
"offsets": [
[
1529,
1537
]
],
"normalized": []
},
{
"id": "1478",
"type": "other_name",
"text": [
"ICK-1 binding"
],
"offsets": [
[
1562,
1575
]
],
"normalized": []
},
{
"id": "1479",
"type": "DNA_domain_or_region",
"text": [
"GOS19.1 promoter"
],
"offsets": [
[
1592,
1608
]
],
"normalized": []
},
{
"id": "1480",
"type": "cell_line",
"text": [
"U937 cells"
],
"offsets": [
[
1612,
1622
]
],
"normalized": []
},
{
"id": "1481",
"type": "cell_line",
"text": [
"Jurkat cells"
],
"offsets": [
[
1663,
1675
]
],
"normalized": []
},
{
"id": "1482",
"type": "protein_family_or_group",
"text": [
"MNP protein"
],
"offsets": [
[
1697,
1708
]
],
"normalized": []
},
{
"id": "1483",
"type": "DNA_domain_or_region",
"text": [
"MNP site"
],
"offsets": [
[
1727,
1735
]
],
"normalized": []
},
{
"id": "1484",
"type": "protein_family_or_group",
"text": [
"transcription factor"
],
"offsets": [
[
1756,
1776
]
],
"normalized": []
},
{
"id": "1485",
"type": "cell_type",
"text": [
"hematopoietic cells"
],
"offsets": [
[
1793,
1812
]
],
"normalized": []
}
] | [] | [] | [] |
1486 | 96055286 | [
{
"id": "1487",
"type": "title",
"text": [
"The effect of Toremifene on the expression of some genes in human mononuclear cells."
],
"offsets": [
[
0,
84
]
]
},
{
"id": "1488",
"type": "abstract",
"text": [
"Toremifene exerts multiple and varied effects on the gene expression of human peripheral mononuclear cells. After short-term, in vitro exposure to therapeutical levels, distinct changes in P-glycoprotein, steroid receptors, p53 and Bcl-2 expression take place. In view of the increasing use of antiestrogens in cancer therapy and prevention, there is obvious merit in long-term in vivo studies to be conducted."
],
"offsets": [
[
85,
495
]
]
}
] | [
{
"id": "1489",
"type": "other_organic_compound",
"text": [
"Toremifene"
],
"offsets": [
[
14,
24
]
],
"normalized": []
},
{
"id": "1490",
"type": "cell_type",
"text": [
"human mononuclear cells"
],
"offsets": [
[
60,
83
]
],
"normalized": []
},
{
"id": "1491",
"type": "other_organic_compound",
"text": [
"Toremifene"
],
"offsets": [
[
85,
95
]
],
"normalized": []
},
{
"id": "1492",
"type": "other_name",
"text": [
"gene expression"
],
"offsets": [
[
138,
153
]
],
"normalized": []
},
{
"id": "1493",
"type": "cell_type",
"text": [
"human peripheral mononuclear cells"
],
"offsets": [
[
157,
191
]
],
"normalized": []
},
{
"id": "1494",
"type": "other_name",
"text": [
"vitro exposure"
],
"offsets": [
[
214,
228
]
],
"normalized": []
},
{
"id": "1495",
"type": "other_name",
"text": [
"therapeutical levels"
],
"offsets": [
[
232,
252
]
],
"normalized": []
},
{
"id": "1496",
"type": "(AND other_name other_name other_name other_name)",
"text": [
"P-glycoprotein, steroid receptors, p53 and Bcl-2 expression"
],
"offsets": [
[
274,
333
]
],
"normalized": []
},
{
"id": "1497",
"type": "",
"text": [
"P-glycoprotein"
],
"offsets": [
[
274,
288
]
],
"normalized": []
},
{
"id": "1498",
"type": "",
"text": [
"steroid receptors"
],
"offsets": [
[
290,
307
]
],
"normalized": []
},
{
"id": "1499",
"type": "",
"text": [
"p53"
],
"offsets": [
[
309,
312
]
],
"normalized": []
},
{
"id": "1500",
"type": "",
"text": [
"Bcl-2"
],
"offsets": [
[
317,
322
]
],
"normalized": []
},
{
"id": "1501",
"type": "",
"text": [
"expression"
],
"offsets": [
[
323,
333
]
],
"normalized": []
},
{
"id": "1502",
"type": "lipid",
"text": [
"antiestrogens"
],
"offsets": [
[
379,
392
]
],
"normalized": []
},
{
"id": "1503",
"type": "other_name",
"text": [
"cancer therapy"
],
"offsets": [
[
396,
410
]
],
"normalized": []
},
{
"id": "1504",
"type": "other_name",
"text": [
"prevention"
],
"offsets": [
[
415,
425
]
],
"normalized": []
},
{
"id": "1505",
"type": "other_name",
"text": [
"long-term in vivo studies"
],
"offsets": [
[
453,
478
]
],
"normalized": []
}
] | [] | [] | [] |
End of preview. Expand
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Dataset Card for GENIA Term Corpus
The identification of linguistic expressions referring to entities of interest in molecular biology such as proteins, genes and cells is a fundamental task in biomolecular text mining. The GENIA technical term annotation covers the identification of physical biological entities as well as other important terms. The corpus annotation covers the full 1,999 abstracts of the primary GENIA corpus.
Citation Information
@inproceedings{10.5555/1289189.1289260,
author = {Ohta, Tomoko and Tateisi, Yuka and Kim, Jin-Dong},
title = {The GENIA Corpus: An Annotated Research Abstract Corpus in Molecular Biology Domain},
year = {2002},
publisher = {Morgan Kaufmann Publishers Inc.},
address = {San Francisco, CA, USA},
booktitle = {Proceedings of the Second International Conference on Human Language Technology Research},
pages = {82–86},
numpages = {5},
location = {San Diego, California},
series = {HLT '02}
}
@article{Kim2003GENIAC,
title={GENIA corpus - a semantically annotated corpus for bio-textmining},
author={Jin-Dong Kim and Tomoko Ohta and Yuka Tateisi and Junichi Tsujii},
journal={Bioinformatics},
year={2003},
volume={19 Suppl 1},
pages={
i180-2
}
}
@inproceedings{10.5555/1567594.1567610,
author = {Kim, Jin-Dong and Ohta, Tomoko and Tsuruoka, Yoshimasa and Tateisi, Yuka and Collier, Nigel},
title = {Introduction to the Bio-Entity Recognition Task at JNLPBA},
year = {2004},
publisher = {Association for Computational Linguistics},
address = {USA},
booktitle = {Proceedings of the International Joint Workshop on Natural Language Processing in Biomedicine and Its
Applications},
pages = {70–75},
numpages = {6},
location = {Geneva, Switzerland},
series = {JNLPBA '04}
}
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