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100 | PMID-8186192 | [
{
"id": "PMID-8186192__text",
"type": "abstract",
"text": [
"Some antioxidants inhibit, in a co-ordinate fashion, the production of tumor necrosis factor-alpha, IL-beta, and IL-6 by human peripheral blood mononuclear cells. \nSome antioxidants, including butylated hydroxyanisole (BHA), tetrahydropapaveroline (THP), nordihydroguiauretic acid, and 10,11-dihydroxyaporphine (DHA), were found to be potent inhibitors of the production of tumor necrosis factor (TNF)-alpha, IL-1 beta, and IL-6 by human peripheral blood mononuclear cells (PBMC) stimulated by lipopolysaccharide (LPS) (IC50s in the low micromolar range). Inhibition of cytokine production was gene selective and not due to general effects on protein synthesis. Inhibition of cytokine production by PBMC was observed also when other inducers were used (staphylococci, silica, zymosan). Much higher concentrations of other antioxidants--including ascorbic acid, trolox, alpha-tocopherol, butylated hydroxytoluene, and the 5-lipoxygenase inhibitor zileuton--did not affect the production of these cytokines. The active compounds did not inhibit IL-1-induced production of IL-6 in fibroblasts, showing the cell selectivity of the effect. Antioxidant-mediated inhibition of cytokine production was correlated with low levels of the corresponding messenger RNAs. Nuclear run-on experiments showed that THP inhibited transcription of the IL-1 beta gene. THP decreased the concentration of the transcription factors NF-kappa B and AP-1 detected in nuclear extracts of PBMC cultured in the presence or absence of LPS. THP and DHA markedly decreased the levels of TNF-alpha and IL-1 beta in the circulation of mice following LPS injection. Thus antioxidants vary widely in potency as inhibitors of the activation of transcription factors and of the transcription of genes for pro-inflammatory cytokines. Coordinate inhibition of the transcription of genes for inflammatory cytokines could provide a strategy for therapy of diseases with inflammatory pathogenesis and for septic shock.\n"
],
"offsets": [
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{
"id": "PMID-8186192_T1",
"type": "Protein",
"text": [
"tumor necrosis factor-alpha"
],
"offsets": [
[
71,
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],
"normalized": []
},
{
"id": "PMID-8186192_T2",
"type": "Protein",
"text": [
"IL-beta"
],
"offsets": [
[
100,
107
]
],
"normalized": []
},
{
"id": "PMID-8186192_T3",
"type": "Protein",
"text": [
"IL-6"
],
"offsets": [
[
113,
117
]
],
"normalized": []
},
{
"id": "PMID-8186192_T4",
"type": "Protein",
"text": [
"tumor necrosis factor (TNF)-alpha"
],
"offsets": [
[
374,
407
]
],
"normalized": []
},
{
"id": "PMID-8186192_T5",
"type": "Protein",
"text": [
"IL-1 beta"
],
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[
409,
418
]
],
"normalized": []
},
{
"id": "PMID-8186192_T6",
"type": "Protein",
"text": [
"IL-6"
],
"offsets": [
[
424,
428
]
],
"normalized": []
},
{
"id": "PMID-8186192_T7",
"type": "Protein",
"text": [
"IL-6"
],
"offsets": [
[
1070,
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],
"normalized": []
},
{
"id": "PMID-8186192_T8",
"type": "Protein",
"text": [
"IL-1 beta"
],
"offsets": [
[
1332,
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]
],
"normalized": []
},
{
"id": "PMID-8186192_T9",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
1555,
1564
]
],
"normalized": []
},
{
"id": "PMID-8186192_T10",
"type": "Protein",
"text": [
"IL-1 beta"
],
"offsets": [
[
1569,
1578
]
],
"normalized": []
},
{
"id": "PMID-8186192_T11",
"type": "Entity",
"text": [
"NF-kappa B"
],
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[
1409,
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]
],
"normalized": []
},
{
"id": "PMID-8186192_T12",
"type": "Entity",
"text": [
"genes"
],
"offsets": [
[
1757,
1762
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],
"normalized": []
}
] | [] | [] | [] |
101 | PMID-1981844 | [
{
"id": "PMID-1981844__text",
"type": "abstract",
"text": [
"Human immunodeficiency virus type-2 gene expression: two enhancers and their activation by T-cell activators. \nThe human immunodeficiency viruses (HIVs) may include a spectrum of retroviruses with varying potential to infect their host, undergo long periods of latent infection, and induce pathology. Since expression of the viruses is in large part regulated by the sequence elements in their long terminal repeats (LTRs), this study was directed to an analysis of the regulatory elements in the HIV-2 LTR. The HIV-2 LTR was found to contain two enhancers. One of these enhancers is, in part, identical to the HIV-1 enhancer. This enhancer in HIV-1 is the T-cell activation response element; in HIV-2, however, it is the second enhancer that is mainly responsible for activation in response to T-cell activators. The second enhancer interacts with two nuclear binding proteins (85 kD and 27 kD mobility) that appear to be required for optimal enhancer function and activation. Observations such as these encourage the speculation that there may be subtle differences in the regulation of HIV-1 and HIV-2 expression that may be relevant to the possible longer latency and reduced pathogenicity of HIV-2.\n"
],
"offsets": [
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0,
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] | [
{
"id": "PMID-1981844_T1",
"type": "Entity",
"text": [
"Human immunodeficiency virus type-2 gene"
],
"offsets": [
[
0,
40
]
],
"normalized": []
},
{
"id": "PMID-1981844_T2",
"type": "Entity",
"text": [
"enhancers"
],
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57,
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]
],
"normalized": []
},
{
"id": "PMID-1981844_T3",
"type": "Entity",
"text": [
"sequence elements"
],
"offsets": [
[
367,
384
]
],
"normalized": []
},
{
"id": "PMID-1981844_T4",
"type": "Entity",
"text": [
"long terminal repeats"
],
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394,
415
]
],
"normalized": []
},
{
"id": "PMID-1981844_T5",
"type": "Entity",
"text": [
"LTRs"
],
"offsets": [
[
417,
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]
],
"normalized": []
},
{
"id": "PMID-1981844_T6",
"type": "Entity",
"text": [
"regulatory elements"
],
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470,
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]
],
"normalized": []
},
{
"id": "PMID-1981844_T7",
"type": "Entity",
"text": [
"HIV-2 LTR"
],
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[
497,
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]
],
"normalized": []
},
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"id": "PMID-1981844_T8",
"type": "Entity",
"text": [
"HIV-2 LTR"
],
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512,
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],
"normalized": []
},
{
"id": "PMID-1981844_T9",
"type": "Entity",
"text": [
"enhancers"
],
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547,
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]
],
"normalized": []
},
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"id": "PMID-1981844_T10",
"type": "Entity",
"text": [
"enhancers"
],
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571,
580
]
],
"normalized": []
},
{
"id": "PMID-1981844_T11",
"type": "Entity",
"text": [
"HIV-1 enhancer"
],
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611,
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]
],
"normalized": []
},
{
"id": "PMID-1981844_T12",
"type": "Entity",
"text": [
"T-cell activation response element"
],
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[
657,
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]
],
"normalized": []
},
{
"id": "PMID-1981844_T13",
"type": "Entity",
"text": [
"second enhancer"
],
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[
722,
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]
],
"normalized": []
},
{
"id": "PMID-1981844_T14",
"type": "Entity",
"text": [
"enhancer"
],
"offsets": [
[
825,
833
]
],
"normalized": []
}
] | [] | [] | [] |
102 | PMID-1768652 | [
{
"id": "PMID-1768652__text",
"type": "abstract",
"text": [
"Kappa B-specific DNA binding proteins are differentially inhibited by enhancer mutations and biological oxidation. \nKappa B (kappa B) enhancer binding proteins isolated from the nuclei of activated human T cells produce two distinct nucleoprotein complexes when incubated with the kappa B element from the interleukin-2 receptor-alpha (IL-2R alpha) gene. These two DNA-protein complexes are composed of at least four host proteins (p50, p55, p75, p85), each of which shares structural similarity with the v-rel oncogene product. Nuclear expression of these proteins is induced with distinctly biphasic kinetics following phorbol ester activation of T cells (p55/p75 early and p50/p85 late). DNA-protein crosslinking studies have revealed that the more rapidly migrating B2 complex contains both p50 and p55 while the more slowly migrating B1 complex is composed of p50, p55, p75, and p85. Site-directed mutagenesis of the wild-type IL-2R alpha kappa B enhancer (GGGGAATCTCCC) has revealed that the binding of p50 and p55 (B2 complex) is particularly sensitive to alteration of the 5' triplet of deoxyguanosine residues. In contrast, formation of the B1 complex, reflecting the binding of p75 and p85, critically depends upon the more 3' sequences of this enhancer element. DNA binding by all four of these Rel-related factors is blocked by selective chemical modification of lysine and arginine residues, suggesting that both of these basic amino acids are required for binding to the kappa B element. Similarly, covalent modification of free sulfhydryl groups with diamide (reversible) or N-ethylmaleimide (irreversible) results in a complete loss of DNA binding activity. In contrast, mild oxidation with glucose oxidase selectively inhibits p75 and p85 binding while not blocking p50 and p55 interactions. These findings suggest that reduced cysteine thiols play an important role in the DNA binding activity of this family of Rel-related transcription factors.\n"
],
"offsets": [
[
0,
1965
]
]
}
] | [
{
"id": "PMID-1768652_T1",
"type": "Protein",
"text": [
"interleukin-2 receptor-alpha"
],
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[
306,
334
]
],
"normalized": []
},
{
"id": "PMID-1768652_T2",
"type": "Protein",
"text": [
"IL-2R alpha"
],
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[
336,
347
]
],
"normalized": []
},
{
"id": "PMID-1768652_T3",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
432,
435
]
],
"normalized": []
},
{
"id": "PMID-1768652_T4",
"type": "Protein",
"text": [
"p55"
],
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[
437,
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]
],
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},
{
"id": "PMID-1768652_T5",
"type": "Protein",
"text": [
"p75"
],
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442,
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]
],
"normalized": []
},
{
"id": "PMID-1768652_T6",
"type": "Protein",
"text": [
"p85"
],
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447,
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]
],
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},
{
"id": "PMID-1768652_T7",
"type": "Protein",
"text": [
"v-rel"
],
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505,
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]
],
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},
{
"id": "PMID-1768652_T8",
"type": "Protein",
"text": [
"p55"
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658,
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]
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},
{
"id": "PMID-1768652_T9",
"type": "Protein",
"text": [
"p75"
],
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662,
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]
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},
{
"id": "PMID-1768652_T10",
"type": "Protein",
"text": [
"p50"
],
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676,
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]
],
"normalized": []
},
{
"id": "PMID-1768652_T11",
"type": "Protein",
"text": [
"p85"
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680,
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]
],
"normalized": []
},
{
"id": "PMID-1768652_T12",
"type": "Protein",
"text": [
"p50"
],
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]
],
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},
{
"id": "PMID-1768652_T13",
"type": "Protein",
"text": [
"p55"
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[
803,
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]
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},
{
"id": "PMID-1768652_T14",
"type": "Protein",
"text": [
"p50"
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"offsets": [
[
865,
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]
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"normalized": []
},
{
"id": "PMID-1768652_T15",
"type": "Protein",
"text": [
"p55"
],
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870,
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]
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"normalized": []
},
{
"id": "PMID-1768652_T16",
"type": "Protein",
"text": [
"p75"
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875,
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]
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},
{
"id": "PMID-1768652_T17",
"type": "Protein",
"text": [
"p85"
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884,
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],
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},
{
"id": "PMID-1768652_T18",
"type": "Protein",
"text": [
"IL-2R alpha"
],
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932,
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},
{
"id": "PMID-1768652_T19",
"type": "Protein",
"text": [
"p50"
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},
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"id": "PMID-1768652_T20",
"type": "Protein",
"text": [
"p55"
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},
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"id": "PMID-1768652_T21",
"type": "Protein",
"text": [
"p75"
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},
{
"id": "PMID-1768652_T22",
"type": "Protein",
"text": [
"p85"
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1196,
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],
"normalized": []
},
{
"id": "PMID-1768652_T23",
"type": "Protein",
"text": [
"glucose oxidase"
],
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1707,
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],
"normalized": []
},
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"id": "PMID-1768652_T24",
"type": "Protein",
"text": [
"p75"
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1744,
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"normalized": []
},
{
"id": "PMID-1768652_T25",
"type": "Protein",
"text": [
"p85"
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[
1752,
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"normalized": []
},
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"id": "PMID-1768652_T26",
"type": "Protein",
"text": [
"p50"
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},
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"id": "PMID-1768652_T27",
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"p55"
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"id": "PMID-1768652_T28",
"type": "Entity",
"text": [
"Kappa B"
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0,
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"id": "PMID-1768652_T29",
"type": "Entity",
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"enhancer"
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"id": "PMID-1768652_T30",
"type": "Entity",
"text": [
"Kappa B (kappa B) enhancer"
],
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116,
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{
"id": "PMID-1768652_T31",
"type": "Entity",
"text": [
"nucleoprotein complexes"
],
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233,
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],
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},
{
"id": "PMID-1768652_T32",
"type": "Entity",
"text": [
"kappa B element"
],
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[
281,
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],
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},
{
"id": "PMID-1768652_T33",
"type": "Entity",
"text": [
"DNA-protein complexes"
],
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[
365,
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]
],
"normalized": []
},
{
"id": "PMID-1768652_T34",
"type": "Entity",
"text": [
"B2 complex"
],
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[
770,
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]
],
"normalized": []
},
{
"id": "PMID-1768652_T35",
"type": "Entity",
"text": [
"B1 complex"
],
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[
839,
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],
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},
{
"id": "PMID-1768652_T36",
"type": "Entity",
"text": [
"kappa B enhancer"
],
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[
944,
960
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],
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},
{
"id": "PMID-1768652_T37",
"type": "Entity",
"text": [
"GGGGAATCTCCC"
],
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[
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],
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},
{
"id": "PMID-1768652_T38",
"type": "Entity",
"text": [
"B2 complex"
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[
1022,
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],
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},
{
"id": "PMID-1768652_T39",
"type": "Entity",
"text": [
"5' triplet of deoxyguanosine residues"
],
"offsets": [
[
1081,
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],
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},
{
"id": "PMID-1768652_T40",
"type": "Entity",
"text": [
"5' triplet"
],
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[
1081,
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},
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"id": "PMID-1768652_T41",
"type": "Entity",
"text": [
"deoxyguanosine residues"
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[
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],
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},
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"type": "Entity",
"text": [
"B1 complex"
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[
1150,
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},
{
"id": "PMID-1768652_T43",
"type": "Entity",
"text": [
"3' sequences of this enhancer element."
],
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[
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]
],
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},
{
"id": "PMID-1768652_T44",
"type": "Entity",
"text": [
"enhancer element"
],
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[
1255,
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]
],
"normalized": []
},
{
"id": "PMID-1768652_T45",
"type": "Entity",
"text": [
"DNA"
],
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[
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]
],
"normalized": []
},
{
"id": "PMID-1768652_T46",
"type": "Entity",
"text": [
"lysine"
],
"offsets": [
[
1375,
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]
],
"normalized": []
},
{
"id": "PMID-1768652_T47",
"type": "Entity",
"text": [
"arginine"
],
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[
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]
],
"normalized": []
},
{
"id": "PMID-1768652_T48",
"type": "Entity",
"text": [
"basic amino acids"
],
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],
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},
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"id": "PMID-1768652_T49",
"type": "Entity",
"text": [
"kappa B element"
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]
],
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},
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"id": "PMID-1768652_T50",
"type": "Entity",
"text": [
"DNA"
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[
1652,
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]
],
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},
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"id": "PMID-1768652_T51",
"type": "Entity",
"text": [
"reduced cysteine thiols"
],
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[
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],
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},
{
"id": "PMID-1768652_T52",
"type": "Entity",
"text": [
"cysteine"
],
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[
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],
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},
{
"id": "PMID-1768652_T53",
"type": "Entity",
"text": [
"DNA"
],
"offsets": [
[
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]
],
"normalized": []
}
] | [] | [
{
"id": "PMID-1768652_1",
"entity_ids": [
"PMID-1768652_T1",
"PMID-1768652_T2"
]
}
] | [
{
"id": "PMID-1768652_R1",
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"arg2_id": "PMID-1768652_T33",
"normalized": []
},
{
"id": "PMID-1768652_R2",
"type": "Subunit-Complex",
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},
{
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},
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},
{
"id": "PMID-1768652_R5",
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},
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},
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"id": "PMID-1768652_R7",
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},
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"normalized": []
},
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"id": "PMID-1768652_R10",
"type": "Subunit-Complex",
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"normalized": []
},
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"type": "Subunit-Complex",
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"arg2_id": "PMID-1768652_T38",
"normalized": []
},
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"type": "Subunit-Complex",
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"arg2_id": "PMID-1768652_T38",
"normalized": []
},
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"type": "Protein-Component",
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},
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"type": "Subunit-Complex",
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"arg2_id": "PMID-1768652_T42",
"normalized": []
},
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"id": "PMID-1768652_R15",
"type": "Subunit-Complex",
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"arg2_id": "PMID-1768652_T42",
"normalized": []
}
] |
103 | PMID-9108409 | [
{
"id": "PMID-9108409__text",
"type": "abstract",
"text": [
"Two distinct pathways of interleukin-5 synthesis in allergen-specific human T-cell clones are suppressed by glucocorticoids. \nGlucocorticoids (GC) have long been used as the most effective agents for the treatment of allergic diseases accompanied by eosinophilia such as chronic asthma and atopic dermatitis. The development of chronic eosinophilic inflammation is dependent on interleukin-5 (IL-5), a selective eosinophil-activating factor, produced by helper T cells. To delineate the regulatory mechanisms of human IL-5 synthesis, we established allergen-specific CD4+ T-cell clones from asthmatic patients. GC efficiently suppressed IL-5 synthesis of T-cell clones activated via either T-cell receptor (TCR) or IL-2 receptor (IL-2R). Induction of IL-5 mRNA upon TCR and IL-2R stimulation was totally inhibited by dexamethasone. Human IL-5 promoter/enhancer-luciferase gene construct transfected to T-cell clones was transcribed on either TCR or IL-2R stimulation and was clearly downregulated by dexamethasone, indicating that the approximately 500-bp human IL-5 gene segment located 5' upstream of the coding region contains activation-inducible enhancer elements responsible for the regulation by GC. Electrophoretic mobility shift assay analysis suggested that AP-1 and NF-kappaB are among the possible targets of GC actions on TCR-stimulated T cells. NF-AT and NF-kappaB were not significantly induced by IL-2 stimulation. Our results showing that GC suppressed IL-5 production by human CD4+ T cells activated by two distinct stimuli, TCR and IL-2R stimulation, underscore the efficacy of GC in the treatment of allergic diseases via suppression of T-cell IL-5 synthesis.\n"
],
"offsets": [
[
0,
1680
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]
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] | [
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"id": "PMID-9108409_T1",
"type": "Protein",
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"interleukin-5"
],
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[
25,
38
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{
"id": "PMID-9108409_T2",
"type": "Protein",
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"interleukin-5"
],
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[
378,
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"id": "PMID-9108409_T3",
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"IL-5"
],
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393,
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"id": "PMID-9108409_T4",
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"IL-5"
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"id": "PMID-9108409_T5",
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"id": "PMID-9108409_T6",
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"id": "PMID-9108409_T9",
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"IL-2"
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"id": "PMID-9108409_T10",
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"IL-5"
],
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},
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"id": "PMID-9108409_T11",
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"CD4"
],
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"id": "PMID-9108409_T12",
"type": "Protein",
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"IL-5"
],
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1664,
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},
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"id": "PMID-9108409_T13",
"type": "Entity",
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"IL-2 receptor"
],
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]
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},
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"id": "PMID-9108409_T14",
"type": "Entity",
"text": [
"IL-2R"
],
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},
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"id": "PMID-9108409_T15",
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"gene segment"
],
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},
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"id": "PMID-9108409_T16",
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"5' upstream"
],
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1088,
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},
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"id": "PMID-9108409_T17",
"type": "Entity",
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"activation-inducible enhancer elements"
],
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1130,
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],
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},
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"id": "PMID-9108409_T18",
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"enhancer elements"
],
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1151,
1168
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},
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"id": "PMID-9108409_T19",
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],
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1268,
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},
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"id": "PMID-9108409_T20",
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"id": "PMID-9108409_T21",
"type": "Entity",
"text": [
"NF-kappaB"
],
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1369,
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],
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}
] | [] | [
{
"id": "PMID-9108409_1",
"entity_ids": [
"PMID-9108409_T2",
"PMID-9108409_T3"
]
}
] | [
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},
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"type": "Protein-Component",
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"arg2_id": "PMID-9108409_T15",
"normalized": []
}
] |
104 | PMID-8617207 | [
{
"id": "PMID-8617207__text",
"type": "abstract",
"text": [
"GATA transcription factors associate with a novel class of nuclear bodies in erythroblasts and megakaryocytes. \nThe nuclear distribution of GATA transcription factors in murine haemopoietic cells was examined by indirect immunofluorescence. Specific bright foci of GATA-1 fluorescence were observed in erythroleukaemia cells and primary murine erythroblasts and megakaryocytes, in addition to diffuse nucleoplasmic localization. These foci, which were preferentially found adjacent to nucleoli or at the nuclear periphery, did not represent sites of active transcription or binding of GATA-1 to consensus sites in the beta-globin loci. Immunoelectron microscopy demonstrated the presence of intensely labelled structures likely to represent the GATA-1 foci seen by immunofluorescence. The GATA-1 nuclear bodies differed from previously described nuclear structures and there was no co-localization with nuclear antigens involved in RNA processing or other ubiquitous (Spl, c-Jun and TBP) or haemopoietic (NF-E2) transcription factors. Interestingly, GATA-2 and GATA-3 proteins also localized to the same nuclear bodies in cell lines co-expressing GATA-1 and -2 or GATA-1 and -3 gene products. This pattern of distribution is, thus far, unique to the GATA transcription factors and suggests a protein-protein interaction with other components of the nuclear bodies via the GATA zinc finger domain.\n"
],
"offsets": [
[
0,
1397
]
]
}
] | [
{
"id": "PMID-8617207_T1",
"type": "Protein",
"text": [
"GATA-1"
],
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[
265,
271
]
],
"normalized": []
},
{
"id": "PMID-8617207_T2",
"type": "Protein",
"text": [
"GATA-1"
],
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[
585,
591
]
],
"normalized": []
},
{
"id": "PMID-8617207_T3",
"type": "Protein",
"text": [
"beta-globin"
],
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[
618,
629
]
],
"normalized": []
},
{
"id": "PMID-8617207_T4",
"type": "Protein",
"text": [
"GATA-1"
],
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[
745,
751
]
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"normalized": []
},
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"id": "PMID-8617207_T5",
"type": "Protein",
"text": [
"GATA-1"
],
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[
789,
795
]
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"normalized": []
},
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"id": "PMID-8617207_T6",
"type": "Protein",
"text": [
"c-Jun"
],
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[
973,
978
]
],
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},
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"id": "PMID-8617207_T7",
"type": "Protein",
"text": [
"TBP"
],
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[
983,
986
]
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},
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"id": "PMID-8617207_T8",
"type": "Protein",
"text": [
"GATA-2"
],
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"id": "PMID-8617207_T9",
"type": "Protein",
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"GATA-3"
],
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1061,
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},
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"id": "PMID-8617207_T10",
"type": "Protein",
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"GATA-1"
],
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1147,
1153
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},
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"id": "PMID-8617207_T11",
"type": "Protein",
"text": [
"-2"
],
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1158,
1160
]
],
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},
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"id": "PMID-8617207_T12",
"type": "Protein",
"text": [
"GATA-1"
],
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1164,
1170
]
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"normalized": []
},
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"id": "PMID-8617207_T13",
"type": "Protein",
"text": [
"-3"
],
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[
1175,
1177
]
],
"normalized": []
},
{
"id": "PMID-8617207_T14",
"type": "Entity",
"text": [
"consensus sites"
],
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595,
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]
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},
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"id": "PMID-8617207_T15",
"type": "Entity",
"text": [
"loci"
],
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630,
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]
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"id": "PMID-8617207_T16",
"type": "Entity",
"text": [
"GATA zinc finger domain"
],
"offsets": [
[
1372,
1395
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],
"normalized": []
}
] | [] | [] | [
{
"id": "PMID-8617207_R1",
"type": "Protein-Component",
"arg1_id": "PMID-8617207_T3",
"arg2_id": "PMID-8617207_T14",
"normalized": []
}
] |
105 | PMID-8530384 | [
{
"id": "PMID-8530384__text",
"type": "abstract",
"text": [
"Functional characterization of the murine homolog of the B cell-specific coactivator BOB.1/OBF.1. \nB cell-specific transcriptional promoter activity mediated by the octamer motif requires the Oct1 or Oct2 protein and additional B cell-restricted cofactors. One such cofactor, BOB.1/OBF.1, was recently isolated from human B cells. Here, we describe the isolation and detailed characterization of the murine homolog. Full-length cDNAs and genomic clones were isolated, and the gene structure was determined. Comparison of the deduced amino acids shows 88% sequence identity between mouse and human BOB.1/OBF.1. The NH2-terminal 126 amino acids of BOB.1/OBF.1 are both essential and sufficient for interaction with the POU domains of either Oct1 or Oct2. This protein-protein interaction does not require the simultaneous binding of Oct proteins to DNA, and high resolution footprinting of the Oct-DNA interaction reveals that binding of BOB.1/OBF.1 to Oct1 or Oct2 does not alter the interaction with DNA. BOB.1/OBF.1 can efficiently activate octamer-dependent promoters in fibroblasts; however, it fails to stimulate octamer-dependent enhancer activity. Fusion of subdomains of BOB.1/OBF.1 with the GAL4 DNA binding domain reveals that both NH2- and COOH-terminal domains of BOB.1/OBF.1 contribute to full transactivation function, the COOH-terminal domain is more efficient in this transactivation assay. Consistent with the failure of full-length BOB.1/OBF.1 to stimulate octamer-dependent enhancer elements in non B cells, the GAL4 fusions likewise only stimulate from a promoter-proximal position.\n"
],
"offsets": [
[
0,
1602
]
]
}
] | [
{
"id": "PMID-8530384_T1",
"type": "Protein",
"text": [
"BOB.1"
],
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[
85,
90
]
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"normalized": []
},
{
"id": "PMID-8530384_T2",
"type": "Protein",
"text": [
"OBF.1"
],
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[
91,
96
]
],
"normalized": []
},
{
"id": "PMID-8530384_T3",
"type": "Protein",
"text": [
"Oct1"
],
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[
192,
196
]
],
"normalized": []
},
{
"id": "PMID-8530384_T4",
"type": "Protein",
"text": [
"Oct2"
],
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[
200,
204
]
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"id": "PMID-8530384_T5",
"type": "Protein",
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],
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276,
281
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"id": "PMID-8530384_T6",
"type": "Protein",
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],
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282,
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"id": "PMID-8530384_T7",
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"id": "PMID-8530384_T8",
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603,
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"id": "PMID-8530384_T9",
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646,
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"id": "PMID-8530384_T10",
"type": "Protein",
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"OBF.1"
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652,
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},
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"id": "PMID-8530384_T11",
"type": "Protein",
"text": [
"Oct1"
],
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[
739,
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},
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"id": "PMID-8530384_T12",
"type": "Protein",
"text": [
"Oct2"
],
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747,
751
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},
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"id": "PMID-8530384_T13",
"type": "Protein",
"text": [
"BOB.1"
],
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936,
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"id": "PMID-8530384_T14",
"type": "Protein",
"text": [
"OBF.1"
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942,
947
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},
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"id": "PMID-8530384_T15",
"type": "Protein",
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"Oct1"
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951,
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"id": "PMID-8530384_T16",
"type": "Protein",
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"Oct2"
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"OBF.1"
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1011,
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"BOB.1"
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1178,
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},
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"id": "PMID-8530384_T20",
"type": "Protein",
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"OBF.1"
],
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1184,
1189
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},
{
"id": "PMID-8530384_T21",
"type": "Protein",
"text": [
"GAL4"
],
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[
1199,
1203
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},
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"id": "PMID-8530384_T22",
"type": "Protein",
"text": [
"BOB.1"
],
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1275,
1280
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"id": "PMID-8530384_T23",
"type": "Protein",
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"OBF.1"
],
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[
1281,
1286
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},
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"id": "PMID-8530384_T24",
"type": "Protein",
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"BOB.1"
],
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1449,
1454
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},
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"id": "PMID-8530384_T25",
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"OBF.1"
],
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1455,
1460
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},
{
"id": "PMID-8530384_T26",
"type": "Protein",
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"GAL4"
],
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[
1530,
1534
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},
{
"id": "PMID-8530384_T27",
"type": "Entity",
"text": [
"transcriptional promoter"
],
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[
115,
139
]
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},
{
"id": "PMID-8530384_T28",
"type": "Entity",
"text": [
"octamer motif"
],
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[
165,
178
]
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},
{
"id": "PMID-8530384_T29",
"type": "Entity",
"text": [
"cDNAs"
],
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[
428,
433
]
],
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},
{
"id": "PMID-8530384_T30",
"type": "Entity",
"text": [
"genomic clones"
],
"offsets": [
[
438,
452
]
],
"normalized": []
},
{
"id": "PMID-8530384_T31",
"type": "Entity",
"text": [
"NH2-terminal 126 amino acids"
],
"offsets": [
[
614,
642
]
],
"normalized": []
},
{
"id": "PMID-8530384_T32",
"type": "Entity",
"text": [
"POU domains"
],
"offsets": [
[
717,
728
]
],
"normalized": []
},
{
"id": "PMID-8530384_T33",
"type": "Entity",
"text": [
"DNA"
],
"offsets": [
[
847,
850
]
],
"normalized": []
},
{
"id": "PMID-8530384_T34",
"type": "Entity",
"text": [
"DNA"
],
"offsets": [
[
896,
899
]
],
"normalized": []
},
{
"id": "PMID-8530384_T35",
"type": "Entity",
"text": [
"DNA"
],
"offsets": [
[
1000,
1003
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],
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},
{
"id": "PMID-8530384_T36",
"type": "Entity",
"text": [
"octamer-dependent promoters"
],
"offsets": [
[
1042,
1069
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],
"normalized": []
},
{
"id": "PMID-8530384_T37",
"type": "Entity",
"text": [
"octamer"
],
"offsets": [
[
1042,
1049
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],
"normalized": []
},
{
"id": "PMID-8530384_T38",
"type": "Entity",
"text": [
"promoters"
],
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[
1060,
1069
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},
{
"id": "PMID-8530384_T39",
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106 | PMID-9828130 | [
{
"id": "PMID-9828130__text",
"type": "abstract",
"text": [
"Cloning of ARE-containing genes by AU-motif-directed display. \nA procedure suitable for cloning labile mRNAs that contain AU motifs is presented (AU-DD). These motifs are regulatory sequences within the so-called AU-rich elements (AREs) often found in 3' untranslated regions of genes such as cytokines, proto-oncogenes, and transcription factors. AU-DD is an AU-motif-directed differential display that permits the identification of ARE-containing genes differentially expressed after cell activation. It has been applied to peripheral blood monocytes and a T cell clone to isolate 59 cDNA fragments associated to activation. Fourteen percent of isolated fragments belong to already known genes that certainly are cytokines and transduction/transcription factors. The remaining 86% correspond to unknown genes of which 92% have been confirmed to be differentially expressed. These data demonstrate the efficiency of the system and support the notion that numerous genes falling into those categories remain unidentified and that they can be cloned by this method. Copyright 1998 Academic Press.\n"
],
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] | [] | [] | [] |
107 | PMID-9277499 | [
{
"id": "PMID-9277499__text",
"type": "abstract",
"text": [
"Distinct mechanisms for N-acetylcysteine inhibition of cytokine-induced E-selectin and VCAM-1 expression. \nWe have examined the effects of N-acetyl-L-cysteine (NAC), a well-characterized, thiol-containing antioxidant, on agonist-induced monocytic cell adhesion to endothelial cells (EC). NAC inhibited interleukin-1 (IL-1 beta)-induced, but not basal, adhesion with 50% inhibition at approximately 20 mM. Monocytic cell adhesion to EC in response to tumor necrosis factor-alpha (TNF-alpha), lipopolysaccharide (LPS), alpha-thrombin, or phorbol 12-myristate 13-acetate (PMA) was similarly inhibited by NAC. Unlike published studies with pyrrolidinedithiocarbamate, which specifically inhibited vascular cell adhesion molecule 1 (VCAM-1), NAC inhibited IL-1 beta-induced mRNA and cell surface expression of both E-selectin and VCAM-1. NAC had no effect on the half-life of E-selectin or VCAM-1 mRNA. Although NAC reduced nuclear factor-kappa B (NF-kappa B) activation in EC as measured by gel-shift assays using an oligonucleotide probe corresponding to the consensus NF-kappa B binding sites of the VCAM-1 gene (VCAM-NF-kappa B), the antioxidant had no appreciable effect when an oligomer corresponding to the consensus NF-kappa B binding site of the E-selectin gene (E-selectin-NF-kappa B) was used. Because NF-kappa B has been reported to be redox sensitive, we studied the effects of NAC on the EC redox environment. NAC caused an expected dramatic increase in the reduced glutathione (GSH) levels in EC. In vitro studies demonstrated that whereas the binding affinity of NF-kappa B to the VCAM-NF-kappa B oligomer peaked at a GSH-to-oxidized glutathione (GSSG) ratio of approximately 200 and decreased at higher ratios, the binding to the E-selectin-NF-kappa B oligomer appeared relatively unaffected even at ratios > 400, i.e., those achieved in EC treated with 40 mM NAC. These results suggest that NF-kappa B binding to its consensus sequences in the VCAM-1 and E-selectin gene exhibits marked differences in redox sensitivity, allowing for differential gene expression regulated by the same transcription factor. Our data also demonstrate that NAC increases the GSH-to-GSSG ratio within the EC suggesting one possible mechanism through which this antioxidant inhibits agonist-induced monocyte adhesion to EC.\n"
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"type": "Protein-Component",
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"normalized": []
},
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"type": "Protein-Component",
"arg1_id": "PMID-9277499_T15",
"arg2_id": "PMID-9277499_T36",
"normalized": []
}
] |
108 | PMID-9710149 | [
{
"id": "PMID-9710149__text",
"type": "abstract",
"text": [
"Dimethyldithiocarbamate inhibits in vitro activation of primary human CD4+ T lymphocytes. \nDithiocarbamates (DTC), a diverse group of industrial and therapeutic chemicals, have been reported to inhibit, enhance or have no effect on the immune system. These apparent inconsistencies reflect the complexity of the DTCs biological activities and are probably due in part to differences in dose, route of exposure, animal species used and/or specific compound tested. The studies described herein were undertaken to investigate the immunotoxicity of one member of this family, dimethyldithiocarbamate (DMDTC). We demonstrate that 0.1-0.5 microM DMDTC inhibits TNF-alpha-induced activation of NF-kappaB in primary human CD4+ T cells. This inhibition is not accompanied by a loss in viability, and DMDTC-treated T cells retain other active signaling pathways throughout the exposure duration. The inhibition of NF-kappaB is apparently permanent as DMDTC-treated T cells did not regain normal TNF-alpha activation, even after 72 h in culture. DMDTC does not appear to alter NF-kappaB directly as pre-incubation of nuclear extracts with DMDTC does not diminish binding activity of this protein. We further demonstrate that 0.1-0.5 microM DMDTC inhibits intracellular IL-2 production and decreases surface expression of CD25 (the alpha subunit of the IL-2 receptor) in T cells stimulated with phorbol ester. These data demonstrate that DMDTC is a potent immunosuppressive compound in vitro.\n"
],
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[
0,
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"id": "PMID-9710149_T1",
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"id": "PMID-9710149_T2",
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] | [] | [] | [] |
109 | PMID-9015187 | [
{
"id": "PMID-9015187__text",
"type": "abstract",
"text": [
"Impaired induction of c-fos/c-jun genes and of transcriptional regulatory proteins binding distinct c-fos/c-jun promoter elements in activated human T cells during aging. \nThe activation of transcriptional factor c-Fos/c-Jun AP-1 is essential for normal T cell responsiveness and is often impaired in T cells during aging. In the present study, we investigated whether aberrancies in the regulation of c-fos/c-jun at the mRNA or protein level might underlie the age-associated impairments of AP-1 in human T cells. Whereas T cells from young subjects stimulated with cross-linked anti-CD3epsilon mAb OKT3 plus PMA or with the lectin PHA plus PMA demonstrated considerable increases in c-Fos protein expression, the expression of c-Fos but not c-Jun was markedly reduced in stimulated T cells from certain elderly subjects. In addition, RNase protection assays revealed that anti-CD3/PMA-stimulated T cells from a substantial proportion of elderly subjects exhibited decreased levels of c-fos and/or c-jun mRNA compared to T cells from young subjects. Using electrophoretic mobility shift assays, the levels of nuclear regulatory proteins recognizing the AP-1 consensus TRE motif, the proximal c-jun TRE-like promoter element, and the c-fos serum response element (SRE) were determined in resting and stimulated T cells. Although the stimulation of T cells from young subjects resulted in coordinated increases of nuclear protein complexes binding the AP-1 TRE, c-jun TRE, and c-fos SRE DNA sequence motifs, age-related reductions in the activation of AP-1 were accompanied by decreased levels of c-jun TRE and c-fos SRE binding complexes. Furthermore, the nuclear protein complexes binding the SRE motif induced in activated T cells of young and elderly subjects contained serum response factor and Elk-1 pointing toward age-related defects in the activation of transcriptional regulatory proteins distinct from c-jun/AP-1. These results suggest that underlying aberrancies in the induction of c-fos/c-jun as well as their nuclear regulatory proteins may contribute to the age-related impairments of AP-1 activation in human T cells.\n"
],
"offsets": [
[
0,
2134
]
]
}
] | [
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"id": "PMID-9015187_T1",
"type": "Protein",
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],
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22,
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"c-jun"
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"id": "PMID-9015187_T3",
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"id": "PMID-9015187_T4",
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106,
111
]
],
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"id": "PMID-9015187_T5",
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],
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"id": "PMID-9015187_T7",
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402,
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"id": "PMID-9015187_T9",
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"c-Fos"
],
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685,
690
]
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},
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"id": "PMID-9015187_T12",
"type": "Protein",
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"c-Fos"
],
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[
729,
734
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},
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"id": "PMID-9015187_T13",
"type": "Protein",
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"c-Jun"
],
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},
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"id": "PMID-9015187_T14",
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"c-fos"
],
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986,
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},
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"id": "PMID-9015187_T15",
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"c-jun"
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999,
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1193,
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"id": "PMID-9015187_T17",
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"id": "PMID-9015187_T18",
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"c-jun"
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1461,
1466
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],
"normalized": []
},
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"id": "PMID-9015187_T19",
"type": "Protein",
"text": [
"c-fos"
],
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1476,
1481
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"normalized": []
},
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"id": "PMID-9015187_T20",
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"c-jun"
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},
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"id": "PMID-9015187_T21",
"type": "Protein",
"text": [
"c-fos"
],
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[
1610,
1615
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],
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},
{
"id": "PMID-9015187_T22",
"type": "Protein",
"text": [
"serum response factor"
],
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[
1773,
1794
]
],
"normalized": []
},
{
"id": "PMID-9015187_T23",
"type": "Protein",
"text": [
"Elk-1"
],
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[
1799,
1804
]
],
"normalized": []
},
{
"id": "PMID-9015187_T24",
"type": "Protein",
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"c-jun"
],
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1912,
1917
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],
"normalized": []
},
{
"id": "PMID-9015187_T25",
"type": "Protein",
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"c-fos"
],
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[
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1999
]
],
"normalized": []
},
{
"id": "PMID-9015187_T26",
"type": "Protein",
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"c-jun"
],
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]
],
"normalized": []
},
{
"id": "PMID-9015187_T27",
"type": "Entity",
"text": [
"promoter elements"
],
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112,
129
]
],
"normalized": []
},
{
"id": "PMID-9015187_T28",
"type": "Entity",
"text": [
"AP-1"
],
"offsets": [
[
225,
229
]
],
"normalized": []
},
{
"id": "PMID-9015187_T29",
"type": "Entity",
"text": [
"AP-1"
],
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492,
496
]
],
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},
{
"id": "PMID-9015187_T30",
"type": "Entity",
"text": [
"CD3"
],
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[
879,
882
]
],
"normalized": []
},
{
"id": "PMID-9015187_T31",
"type": "Entity",
"text": [
"AP-1 consensus TRE motif"
],
"offsets": [
[
1154,
1178
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],
"normalized": []
},
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"id": "PMID-9015187_T32",
"type": "Entity",
"text": [
"AP-1"
],
"offsets": [
[
1154,
1158
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],
"normalized": []
},
{
"id": "PMID-9015187_T33",
"type": "Entity",
"text": [
"TRE-like promoter element"
],
"offsets": [
[
1199,
1224
]
],
"normalized": []
},
{
"id": "PMID-9015187_T34",
"type": "Entity",
"text": [
"serum response element"
],
"offsets": [
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1240,
1262
]
],
"normalized": []
},
{
"id": "PMID-9015187_T35",
"type": "Entity",
"text": [
"SRE"
],
"offsets": [
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1264,
1267
]
],
"normalized": []
},
{
"id": "PMID-9015187_T36",
"type": "Entity",
"text": [
"nuclear protein complexes"
],
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1413,
1438
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],
"normalized": []
},
{
"id": "PMID-9015187_T37",
"type": "Entity",
"text": [
"DNA sequence motifs"
],
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1486,
1505
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],
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},
{
"id": "PMID-9015187_T38",
"type": "Entity",
"text": [
"AP-1"
],
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},
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"id": "PMID-9015187_T39",
"type": "Entity",
"text": [
"binding complexes"
],
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1620,
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"normalized": []
},
{
"id": "PMID-9015187_T40",
"type": "Entity",
"text": [
"nuclear protein complexes"
],
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1656,
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},
{
"id": "PMID-9015187_T41",
"type": "Entity",
"text": [
"SRE motif"
],
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1694,
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"normalized": []
},
{
"id": "PMID-9015187_T42",
"type": "Entity",
"text": [
"/AP-1"
],
"offsets": [
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1917,
1922
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],
"normalized": []
},
{
"id": "PMID-9015187_T43",
"type": "Entity",
"text": [
"AP-1"
],
"offsets": [
[
2100,
2104
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "PMID-9015187_R1",
"type": "Protein-Component",
"arg1_id": "PMID-9015187_T3",
"arg2_id": "PMID-9015187_T27",
"normalized": []
},
{
"id": "PMID-9015187_R2",
"type": "Protein-Component",
"arg1_id": "PMID-9015187_T4",
"arg2_id": "PMID-9015187_T27",
"normalized": []
},
{
"id": "PMID-9015187_R3",
"type": "Subunit-Complex",
"arg1_id": "PMID-9015187_T5",
"arg2_id": "PMID-9015187_T28",
"normalized": []
},
{
"id": "PMID-9015187_R4",
"type": "Subunit-Complex",
"arg1_id": "PMID-9015187_T6",
"arg2_id": "PMID-9015187_T28",
"normalized": []
},
{
"id": "PMID-9015187_R5",
"type": "Protein-Component",
"arg1_id": "PMID-9015187_T16",
"arg2_id": "PMID-9015187_T33",
"normalized": []
},
{
"id": "PMID-9015187_R6",
"type": "Protein-Component",
"arg1_id": "PMID-9015187_T17",
"arg2_id": "PMID-9015187_T34",
"normalized": []
},
{
"id": "PMID-9015187_R7",
"type": "Protein-Component",
"arg1_id": "PMID-9015187_T18",
"arg2_id": "PMID-9015187_T37",
"normalized": []
},
{
"id": "PMID-9015187_R8",
"type": "Protein-Component",
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"arg2_id": "PMID-9015187_T37",
"normalized": []
},
{
"id": "PMID-9015187_R9",
"type": "Subunit-Complex",
"arg1_id": "PMID-9015187_T23",
"arg2_id": "PMID-9015187_T40",
"normalized": []
},
{
"id": "PMID-9015187_R10",
"type": "Subunit-Complex",
"arg1_id": "PMID-9015187_T22",
"arg2_id": "PMID-9015187_T40",
"normalized": []
},
{
"id": "PMID-9015187_R11",
"type": "Subunit-Complex",
"arg1_id": "PMID-9015187_T24",
"arg2_id": "PMID-9015187_T42",
"normalized": []
}
] |
110 | PMID-1464736 | [
{
"id": "PMID-1464736__text",
"type": "abstract",
"text": [
"Phorbol ester reduces constitutive nuclear NF kappa B and inhibits HIV-1 production in mature human monocytic cells. \nNF kappa B is a potent mediator of specific gene expression in human monocytes and has been shown to play a role in transcription of the HIV-1 genome in promonocytic leukemias. There is little information available on the response of NF kappa B to cytokines in normal human monocytes. We have used a 32P-labeled oligonucleotide derived from human immunodeficiency virus (HIV-1) long terminal repeat, which contains a tandem repeat of the NF kappa B binding sequence, as a probe in a gel retardation assay to study this transcription factor. Using this assay, we have detected NF kappa B in extracts of nuclei from normal human monocytes. Treatment of normal monocytes with 12-0-tetradecanoyl phorbol-13-acetate (TPA) for 4-24 h caused the complete disappearance of NF kappa B from nuclear extracts of monocytes. A similar result was obtained with the mature monocytic leukemia cell line THP-1. The constitutive transcription factor SP1 was unaffected by addition of TPA. The disappearance of NF kappa B from the nucleus was concentration dependent between 10 and 50 ng/ml of phorbol ester. In THP-1 cells, TPA also induced a new, faster-migrating NF kappa B species not induced in monocytes. Protein kinase C inhibitor staurosporine, but not cyclic nucleotide-dependent protein kinase inhibitor HA-1004, also dramatically reduced constitutive levels of nuclear NF kappa B. Finally, TPA addition to monocytes infected with HIV-1 inhibited HIV-1 replication, as determined by reverse transcriptase assays, in a concentration-dependent manner. These results are in striking contrast to the increase in nuclear NF kappa B and HIV-1 replication induced by phorbol esters in promonocytic leukemia cells U937 and HL-60, and emphasize the importance of studying cytokine regulation of HIV-1 in normal monocytes.\n"
],
"offsets": [
[
0,
1922
]
]
}
] | [
{
"id": "PMID-1464736_T1",
"type": "Protein",
"text": [
"SP1"
],
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1053
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},
{
"id": "PMID-1464736_T2",
"type": "Entity",
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"NF kappa B"
],
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43,
53
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"normalized": []
},
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"id": "PMID-1464736_T3",
"type": "Entity",
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"NF kappa B"
],
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118,
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},
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"id": "PMID-1464736_T4",
"type": "Entity",
"text": [
"HIV-1 genome"
],
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255,
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},
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"id": "PMID-1464736_T5",
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],
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352,
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},
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"id": "PMID-1464736_T6",
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"text": [
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],
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"id": "PMID-1464736_T7",
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"human immunodeficiency virus (HIV-1) long terminal repeat"
],
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},
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"id": "PMID-1464736_T8",
"type": "Entity",
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"tandem repeat"
],
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"id": "PMID-1464736_T9",
"type": "Entity",
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],
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"id": "PMID-1464736_T10",
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"NF kappa B"
],
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},
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"id": "PMID-1464736_T11",
"type": "Entity",
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"NF kappa B"
],
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},
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"id": "PMID-1464736_T12",
"type": "Entity",
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"NF kappa B"
],
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},
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"id": "PMID-1464736_T13",
"type": "Entity",
"text": [
"NF kappa B"
],
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},
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"id": "PMID-1464736_T14",
"type": "Entity",
"text": [
"cyclic nucleotide"
],
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"id": "PMID-1464736_T15",
"type": "Entity",
"text": [
"NF kappa B"
],
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"id": "PMID-1464736_T16",
"type": "Entity",
"text": [
"NF kappa B"
],
"offsets": [
[
1725,
1735
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],
"normalized": []
}
] | [] | [] | [] |
111 | PMID-2193097 | [
{
"id": "PMID-2193097__text",
"type": "abstract",
"text": [
"Lipopolysaccharide is a potent monocyte/macrophage-specific stimulator of human immunodeficiency virus type 1 expression. \nLipopolysaccharide (LPS) potently stimulates human immunodeficiency virus type 1-long terminal repeat (HIV-1-LTR) CAT constructs transfected into monocyte/macrophage-like cell lines but not a T cell line. This effect appears to be mediated through the induction of nuclear factor kappa B (NF-kappa B). Electrophoretic mobility shift assays demonstrate that LPS induces a DNA binding activity indistinguishable from NF-kappa B in U937 and THP-1 cells. LPS is also shown to dramatically increase HIV-1 production from a chronically infected monocyte/macrophage-like cloned cell line, U1, which produces very low levels of HIV-1 at baseline. The stimulation of viral production from this cell line occurs only if these cells are treated with granulocyte/macrophage colony-stimulating factor (GM-CSF) before treatment with LPS. This stimulation of HIV-1 production is correlated with an increase in the level of HIV-1 RNA and and activation of NF-kappa B. LPS is not able to induce HIV-1 production in a cloned T cell line. The effect of LPS on HIV-1 replication occurs at picogram per milliliter concentrations and may be clinically significant in understanding the variability of the natural history of HIV-1 infection.\n"
],
"offsets": [
[
0,
1341
]
]
}
] | [
{
"id": "PMID-2193097_T1",
"type": "Protein",
"text": [
"CAT"
],
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237,
240
]
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"id": "PMID-2193097_T2",
"type": "Protein",
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"GM-CSF"
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"id": "PMID-2193097_T4",
"type": "Entity",
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"human immunodeficiency virus type 1-long terminal repeat"
],
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224
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226,
235
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"type": "Entity",
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"nuclear factor kappa B"
],
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410
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] | [] | [
{
"id": "PMID-2193097_1",
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]
}
] | [] |
112 | PMID-10438843 | [
{
"id": "PMID-10438843__text",
"type": "abstract",
"text": [
"Thymocyte-thymic epithelial cell interaction leads to high-level replication of human immunodeficiency virus exclusively in mature CD4(+) CD8(-) CD3(+) thymocytes: a critical role for tumor necrosis factor and interleukin-7. \nThis work aims at identifying the thymocyte subpopulation able to support human immunodeficiency virus (HIV) replication under the biological stimuli of the thymic microenvironment. In this report we demonstrate that interaction with thymic epithelial cells (TEC) induces a high-level replication of the T-tropic primary isolate HIV-1(B-LAIp) exclusively in the mature CD4(+) CD8(-) CD3(+) thymocytes. Tumor necrosis factor (TNF) and interleukin-7 (IL-7), secreted during this interaction, are critical cytokines for HIV long terminal repeat transactivation through NF-kappaB-dependent activation. TNF is the major inducer of NF-kappaB and particularly of the p50-p65 complex, whereas IL-7 acts as a cofactor by sustaining the expression of the p75 TNF receptor. The requirement for TNF is further confirmed by the observation that the inability of the intermediate CD4(+) CD8(-) CD3(-) thymocytes to replicate the virus is associated with a defect in TNF production during their interaction with TEC and correlates with the absence of nuclear NF-kappaB activity in these freshly isolated thymocytes. Addition of exogenous TNF to the intermediate thymocyte cultures induces NF-kappaB activity and is sufficient to promote HIV replication in the cocultures with TEC. The other major subpopulation expressing the CD4 receptor, namely, the double-positive (DP) CD4(+) CD8(+) CD3(+/-) thymocytes, despite the entry of the virus, do not produce a significant level of virus, presumably because they are unresponsive to TNF and IL-7. Together, these data suggest that in vivo, despite an efficient entry of the virus in all the CD4(+) subpopulations, a high viral load may be generated exclusively within the mature CD4(+) CD8(-) CD3(+) subset of thymocytes. However, under conditions of inflammatory response after infection, TNF might also be present in the intermediate thymocyte compartment, leading to efficient HIV replication in these cells.\n"
],
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[
0,
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]
}
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"id": "PMID-10438843_T1",
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"CD4"
],
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131,
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]
],
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"id": "PMID-10438843_T2",
"type": "Protein",
"text": [
"tumor necrosis factor"
],
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184,
205
]
],
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{
"id": "PMID-10438843_T3",
"type": "Protein",
"text": [
"interleukin-7"
],
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210,
223
]
],
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},
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"id": "PMID-10438843_T4",
"type": "Protein",
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"CD4"
],
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598
]
],
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},
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"id": "PMID-10438843_T5",
"type": "Protein",
"text": [
"Tumor necrosis factor"
],
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]
],
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},
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"id": "PMID-10438843_T6",
"type": "Protein",
"text": [
"TNF"
],
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]
],
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},
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"id": "PMID-10438843_T7",
"type": "Protein",
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"interleukin-7"
],
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]
],
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},
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"id": "PMID-10438843_T8",
"type": "Protein",
"text": [
"IL-7"
],
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]
],
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},
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"id": "PMID-10438843_T9",
"type": "Protein",
"text": [
"TNF"
],
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[
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]
],
"normalized": []
},
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"id": "PMID-10438843_T10",
"type": "Protein",
"text": [
"p50"
],
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[
886,
889
]
],
"normalized": []
},
{
"id": "PMID-10438843_T11",
"type": "Protein",
"text": [
"p65"
],
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[
890,
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]
],
"normalized": []
},
{
"id": "PMID-10438843_T12",
"type": "Protein",
"text": [
"IL-7"
],
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[
911,
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]
],
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},
{
"id": "PMID-10438843_T13",
"type": "Protein",
"text": [
"p75 TNF receptor"
],
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]
],
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},
{
"id": "PMID-10438843_T14",
"type": "Protein",
"text": [
"TNF"
],
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]
],
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},
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"id": "PMID-10438843_T15",
"type": "Protein",
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"CD4"
],
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]
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},
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"id": "PMID-10438843_T16",
"type": "Protein",
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"TNF"
],
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]
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},
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"id": "PMID-10438843_T17",
"type": "Protein",
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"TNF"
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]
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},
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"id": "PMID-10438843_T18",
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"CD4"
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]
],
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},
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"id": "PMID-10438843_T19",
"type": "Protein",
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"CD4"
],
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]
],
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},
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"id": "PMID-10438843_T20",
"type": "Protein",
"text": [
"TNF"
],
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1740,
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]
],
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},
{
"id": "PMID-10438843_T21",
"type": "Protein",
"text": [
"IL-7"
],
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]
],
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},
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"id": "PMID-10438843_T22",
"type": "Protein",
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"CD4"
],
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]
],
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},
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"id": "PMID-10438843_T23",
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"CD4"
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]
],
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},
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"id": "PMID-10438843_T24",
"type": "Protein",
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"TNF"
],
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]
],
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},
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"id": "PMID-10438843_T25",
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"CD8"
],
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]
],
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},
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"id": "PMID-10438843_T26",
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"CD3"
],
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]
],
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},
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"id": "PMID-10438843_T27",
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"CD8"
],
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]
],
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},
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],
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]
],
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},
{
"id": "PMID-10438843_T29",
"type": "Entity",
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"HIV long terminal repeat"
],
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]
],
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},
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"id": "PMID-10438843_T30",
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"NF-kappaB"
],
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]
],
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},
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"id": "PMID-10438843_T31",
"type": "Entity",
"text": [
"NF-kappaB"
],
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]
],
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},
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"id": "PMID-10438843_T32",
"type": "Entity",
"text": [
"complex"
],
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]
],
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},
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"id": "PMID-10438843_T33",
"type": "Entity",
"text": [
"CD8"
],
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]
],
"normalized": []
},
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"id": "PMID-10438843_T34",
"type": "Entity",
"text": [
"CD3"
],
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[
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]
],
"normalized": []
},
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"id": "PMID-10438843_T35",
"type": "Entity",
"text": [
"NF-kappaB"
],
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]
],
"normalized": []
},
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"id": "PMID-10438843_T36",
"type": "Entity",
"text": [
"NF-kappaB"
],
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]
],
"normalized": []
},
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"id": "PMID-10438843_T37",
"type": "Entity",
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"CD8"
],
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]
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"id": "PMID-10438843_T38",
"type": "Entity",
"text": [
"CD3"
],
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],
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"id": "PMID-10438843_T39",
"type": "Entity",
"text": [
"CD8"
],
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]
],
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},
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"id": "PMID-10438843_T40",
"type": "Entity",
"text": [
"CD3"
],
"offsets": [
[
1950,
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]
],
"normalized": []
}
] | [] | [
{
"id": "PMID-10438843_1",
"entity_ids": [
"PMID-10438843_T5",
"PMID-10438843_T6"
]
},
{
"id": "PMID-10438843_2",
"entity_ids": [
"PMID-10438843_T7",
"PMID-10438843_T8"
]
}
] | [
{
"id": "PMID-10438843_R1",
"type": "Subunit-Complex",
"arg1_id": "PMID-10438843_T10",
"arg2_id": "PMID-10438843_T32",
"normalized": []
},
{
"id": "PMID-10438843_R2",
"type": "Subunit-Complex",
"arg1_id": "PMID-10438843_T11",
"arg2_id": "PMID-10438843_T32",
"normalized": []
}
] |
113 | PMID-1482376 | [
{
"id": "PMID-1482376__text",
"type": "abstract",
"text": [
"Alpha-lipoic acid is a potent inhibitor of NF-kappa B activation in human T cells. \nAcquired immunodeficiency syndrome (AIDS) results from infection with a human immunodeficiency virus (HIV). The long terminal repeat (LTR) region of HIV proviral DNA contains binding sites for nuclear factor kappa B (NF-kappa B), and this transcriptional activator appears to regulate HIV activation. Recent findings suggest an involvement of reactive oxygen species (ROS) in signal transduction pathways leading to NF-kappa B activation. The present study was based on reports that antioxidants which eliminate ROS should block the activation of NF-kappa B and subsequently HIV transcription, and thus antioxidants can be used as therapeutic agents for AIDS. Incubation of Jurkat T cells (1 x 10(6) cells/ml) with a natural thiol antioxidant, alpha-lipoic acid, prior to the stimulation of cells was found to inhibit NF-kappa B activation induced by tumor necrosis factor-alpha (25 ng/ml) or by phorbol 12-myristate 13-acetate (50 ng/ml). The inhibitory action of alpha-lipoic acid was found to be very potent as only 4 mM was needed for a complete inhibition, whereas 20 mM was required for N-acetylcysteine. These results indicate that alpha-lipoic acid may be effective in AIDS therapeutics.\n"
],
"offsets": [
[
0,
1280
]
]
}
] | [
{
"id": "PMID-1482376_T1",
"type": "Protein",
"text": [
"tumor necrosis factor-alpha"
],
"offsets": [
[
935,
962
]
],
"normalized": []
},
{
"id": "PMID-1482376_T2",
"type": "Entity",
"text": [
"NF-kappa B"
],
"offsets": [
[
43,
53
]
],
"normalized": []
},
{
"id": "PMID-1482376_T3",
"type": "Entity",
"text": [
"long terminal repeat (LTR) region"
],
"offsets": [
[
196,
229
]
],
"normalized": []
},
{
"id": "PMID-1482376_T4",
"type": "Entity",
"text": [
"HIV proviral DNA"
],
"offsets": [
[
233,
249
]
],
"normalized": []
},
{
"id": "PMID-1482376_T5",
"type": "Entity",
"text": [
"nuclear factor kappa B"
],
"offsets": [
[
277,
299
]
],
"normalized": []
},
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"id": "PMID-1482376_T6",
"type": "Entity",
"text": [
"NF-kappa B"
],
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[
301,
311
]
],
"normalized": []
},
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"id": "PMID-1482376_T7",
"type": "Entity",
"text": [
"NF-kappa B"
],
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[
500,
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]
],
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},
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"id": "PMID-1482376_T8",
"type": "Entity",
"text": [
"NF-kappa B"
],
"offsets": [
[
631,
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]
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"normalized": []
},
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"id": "PMID-1482376_T9",
"type": "Entity",
"text": [
"NF-kappa B"
],
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"normalized": []
},
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"id": "PMID-1482376_T10",
"type": "Entity",
"text": [
"N-acetylcysteine"
],
"offsets": [
[
1177,
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],
"normalized": []
}
] | [] | [] | [] |
114 | PMID-9334723 | [
{
"id": "PMID-9334723__text",
"type": "abstract",
"text": [
"HIV-1 Vpr suppresses immune activation and apoptosis through regulation of nuclear factor kappa B [see comments] \nThe HIV-1 accessory gene product Vpr can influence viral pathogenesis by affecting viral replication as well as host cell transcription and proliferation. We have investigated the effects of Vpr on host cell activation and confirm that it influences cellular proliferation. However, we have also found that Vpr modulates T-cell receptor (TCR)-triggered apoptosis in a manner similar to that of glucocorticoids. In the absence of TCR-mediated activation, Vpr induces apoptosis whereas in its presence, Vpr interrupts the expected induction of apoptosis. This regulation of apoptosis is linked to Vpr suppression of NF-kappa B activity via the induction of I kappa B, an inhibitor of NF-kappa B. Further, Vpr suppresses expression of IL-2, IL-10, IL-12, TNF alpha and IL-4, all of which are NF-kappa B-dependent. The effects of Vpr could be reversed by RU486. Our finding that Vpr can regulate NF-kappa B supports the hypothesis that some aspects of viral pathogenesis are the consequence of cell dysregulation by Vpr.\n"
],
"offsets": [
[
0,
1131
]
]
}
] | [
{
"id": "PMID-9334723_T1",
"type": "Protein",
"text": [
"Vpr"
],
"offsets": [
[
6,
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]
],
"normalized": []
},
{
"id": "PMID-9334723_T2",
"type": "Protein",
"text": [
"Vpr"
],
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[
147,
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]
],
"normalized": []
},
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"id": "PMID-9334723_T3",
"type": "Protein",
"text": [
"Vpr"
],
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[
305,
308
]
],
"normalized": []
},
{
"id": "PMID-9334723_T4",
"type": "Protein",
"text": [
"Vpr"
],
"offsets": [
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421,
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]
],
"normalized": []
},
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"id": "PMID-9334723_T5",
"type": "Protein",
"text": [
"Vpr"
],
"offsets": [
[
568,
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]
],
"normalized": []
},
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"id": "PMID-9334723_T6",
"type": "Protein",
"text": [
"Vpr"
],
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[
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]
],
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},
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"id": "PMID-9334723_T7",
"type": "Protein",
"text": [
"Vpr"
],
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],
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},
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"id": "PMID-9334723_T8",
"type": "Protein",
"text": [
"Vpr"
],
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[
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]
],
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},
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"id": "PMID-9334723_T9",
"type": "Protein",
"text": [
"IL-2"
],
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]
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"normalized": []
},
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"id": "PMID-9334723_T10",
"type": "Protein",
"text": [
"IL-10"
],
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852,
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]
],
"normalized": []
},
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"id": "PMID-9334723_T11",
"type": "Protein",
"text": [
"TNF alpha"
],
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[
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]
],
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},
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"id": "PMID-9334723_T12",
"type": "Protein",
"text": [
"IL-4"
],
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[
880,
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},
{
"id": "PMID-9334723_T13",
"type": "Protein",
"text": [
"Vpr"
],
"offsets": [
[
940,
943
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"normalized": []
},
{
"id": "PMID-9334723_T14",
"type": "Protein",
"text": [
"Vpr"
],
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[
989,
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]
],
"normalized": []
},
{
"id": "PMID-9334723_T15",
"type": "Protein",
"text": [
"Vpr"
],
"offsets": [
[
1126,
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]
],
"normalized": []
},
{
"id": "PMID-9334723_T16",
"type": "Entity",
"text": [
"nuclear factor kappa B"
],
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[
75,
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],
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},
{
"id": "PMID-9334723_T17",
"type": "Entity",
"text": [
"T-cell receptor"
],
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435,
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],
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},
{
"id": "PMID-9334723_T18",
"type": "Entity",
"text": [
"TCR"
],
"offsets": [
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452,
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]
],
"normalized": []
},
{
"id": "PMID-9334723_T19",
"type": "Entity",
"text": [
"TCR"
],
"offsets": [
[
543,
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]
],
"normalized": []
},
{
"id": "PMID-9334723_T20",
"type": "Entity",
"text": [
"NF-kappa B"
],
"offsets": [
[
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],
"normalized": []
},
{
"id": "PMID-9334723_T21",
"type": "Entity",
"text": [
"NF-kappa B"
],
"offsets": [
[
796,
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],
"normalized": []
},
{
"id": "PMID-9334723_T22",
"type": "Entity",
"text": [
"IL-12"
],
"offsets": [
[
859,
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],
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},
{
"id": "PMID-9334723_T23",
"type": "Entity",
"text": [
"NF-kappa B"
],
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},
{
"id": "PMID-9334723_T24",
"type": "Entity",
"text": [
"NF-kappa B"
],
"offsets": [
[
1006,
1016
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],
"normalized": []
}
] | [] | [] | [] |
115 | PMID-10226884 | [
{
"id": "PMID-10226884__text",
"type": "abstract",
"text": [
"Molecular regulation of cytokine gene expression during the immune response. \nCytokine expression by immune system cells plays an important role in the regulation of the immune response. On first encounter with antigen, naive CD4+ T helper (Th) cells differentiate into cytokine-producing effector cells. Two types of effector cells characterized by their distinct expression of cytokine profiles have been described. Th1 cells produce IL-2 and IFN-gamma, whereas Th2 cells produce IL-4, IL-5, IL-6, IL-10, and IL-13. In many pathological situations, the balance between Th1 and Th2 immune responses determines the outcome of diverse immunologically mediated clinical syndromes including infectious, autoimmune, and allergic diseases. However, the molecular basis for the tissue-specific expression of Th1/Th2-like cytokines has remained elusive. In this review we evaluate the possible in vivo role of different transcription factors and transcriptional mechanisms in T cell differentiation and the immune response.\n"
],
"offsets": [
[
0,
1017
]
]
}
] | [
{
"id": "PMID-10226884_T1",
"type": "Protein",
"text": [
"CD4"
],
"offsets": [
[
226,
229
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],
"normalized": []
},
{
"id": "PMID-10226884_T2",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
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436,
440
]
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"normalized": []
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"id": "PMID-10226884_T3",
"type": "Protein",
"text": [
"IFN-gamma"
],
"offsets": [
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445,
454
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],
"normalized": []
},
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"id": "PMID-10226884_T4",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
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482,
486
]
],
"normalized": []
},
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"id": "PMID-10226884_T5",
"type": "Protein",
"text": [
"IL-5"
],
"offsets": [
[
488,
492
]
],
"normalized": []
},
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"id": "PMID-10226884_T6",
"type": "Protein",
"text": [
"IL-6"
],
"offsets": [
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494,
498
]
],
"normalized": []
},
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"id": "PMID-10226884_T7",
"type": "Protein",
"text": [
"IL-10"
],
"offsets": [
[
500,
505
]
],
"normalized": []
},
{
"id": "PMID-10226884_T8",
"type": "Protein",
"text": [
"IL-13"
],
"offsets": [
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511,
516
]
],
"normalized": []
},
{
"id": "PMID-10226884_T9",
"type": "Entity",
"text": [
"cytokine gene"
],
"offsets": [
[
24,
37
]
],
"normalized": []
},
{
"id": "PMID-10226884_T10",
"type": "Entity",
"text": [
"antigen"
],
"offsets": [
[
211,
218
]
],
"normalized": []
}
] | [] | [] | [] |
116 | PMID-9256234 | [
{
"id": "PMID-9256234__text",
"type": "abstract",
"text": [
"Nuclear levels of NF-kappaB correlate with syncytium-forming capacity of 8e51 cells, expressing a defective HIV virus. \nThe double NF-kappaB site identified in the LTR of the human immunodeficiency virus-1 (HIV-1) has been demonstrated to be necessary for efficient viral transcription. In this report we present the characterisation of NF-kappaB subunits engaged in complexes binding to the HIV-1 NF-kappaB site in human 8e51 T-cells, that harbour a defective HIV-1. At least four different specific NF-kappaB complexes are present in the nucleus of these cells. With the use of specific antibodies we have determined the composition of each complex using electrophoretic mobility shift assays. The results show the presence of several NF-kappaB family members, with the transactivating RelA being engaged in multiple complexes. The importance of NF-kappaB complexes in viral functions has been established comparing the level of NF-kappaB DNA-binding complexes with syncytia-forming activity of 8e51 cells. In fact, 8e51 cells that had almost lost their syncytia-forming capacity were found to contain at least 10 times less active NF-kappaB DNA-binding complex than the actively fusing cells. The correlation is specific as the level of at least three other transcription factors did not change.\n"
],
"offsets": [
[
0,
1299
]
]
}
] | [
{
"id": "PMID-9256234_T1",
"type": "Protein",
"text": [
"RelA"
],
"offsets": [
[
788,
792
]
],
"normalized": []
},
{
"id": "PMID-9256234_T2",
"type": "Entity",
"text": [
"NF-kappaB"
],
"offsets": [
[
18,
27
]
],
"normalized": []
},
{
"id": "PMID-9256234_T3",
"type": "Entity",
"text": [
"double NF-kappaB site"
],
"offsets": [
[
124,
145
]
],
"normalized": []
},
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"id": "PMID-9256234_T4",
"type": "Entity",
"text": [
"NF-kappaB"
],
"offsets": [
[
131,
140
]
],
"normalized": []
},
{
"id": "PMID-9256234_T5",
"type": "Entity",
"text": [
"LTR"
],
"offsets": [
[
164,
167
]
],
"normalized": []
},
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"id": "PMID-9256234_T6",
"type": "Entity",
"text": [
"complexes"
],
"offsets": [
[
367,
376
]
],
"normalized": []
},
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"id": "PMID-9256234_T7",
"type": "Entity",
"text": [
"HIV-1 NF-kappaB site"
],
"offsets": [
[
392,
412
]
],
"normalized": []
},
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"id": "PMID-9256234_T8",
"type": "Entity",
"text": [
"NF-kappaB"
],
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398,
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]
],
"normalized": []
},
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"id": "PMID-9256234_T9",
"type": "Entity",
"text": [
"NF-kappaB complexes"
],
"offsets": [
[
501,
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]
],
"normalized": []
},
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"id": "PMID-9256234_T10",
"type": "Entity",
"text": [
"multiple complexes"
],
"offsets": [
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810,
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]
],
"normalized": []
},
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"id": "PMID-9256234_T11",
"type": "Entity",
"text": [
"NF-kappaB complexes"
],
"offsets": [
[
848,
867
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],
"normalized": []
},
{
"id": "PMID-9256234_T12",
"type": "Entity",
"text": [
"NF-kappaB DNA-binding complexes"
],
"offsets": [
[
931,
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],
"normalized": []
},
{
"id": "PMID-9256234_T13",
"type": "Entity",
"text": [
"NF-kappaB"
],
"offsets": [
[
931,
940
]
],
"normalized": []
},
{
"id": "PMID-9256234_T14",
"type": "Entity",
"text": [
"DNA"
],
"offsets": [
[
941,
944
]
],
"normalized": []
},
{
"id": "PMID-9256234_T15",
"type": "Entity",
"text": [
"NF-kappaB DNA-binding complex"
],
"offsets": [
[
1134,
1163
]
],
"normalized": []
},
{
"id": "PMID-9256234_T16",
"type": "Entity",
"text": [
"NF-kappaB"
],
"offsets": [
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1134,
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],
"normalized": []
},
{
"id": "PMID-9256234_T17",
"type": "Entity",
"text": [
"DNA"
],
"offsets": [
[
1144,
1147
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "PMID-9256234_R1",
"type": "Subunit-Complex",
"arg1_id": "PMID-9256234_T1",
"arg2_id": "PMID-9256234_T10",
"normalized": []
}
] |
117 | PMID-8195215 | [
{
"id": "PMID-8195215__text",
"type": "abstract",
"text": [
"An intricate arrangement of binding sites for the Ets family of transcription factors regulates activity of the alpha 4 integrin gene promoter. \nalpha 4 integrins mediate cell-cell and cell-extracellular matrix interactions that are critical for maturation and function of the immune system as well as differentiation of skeletal muscle. Here we examine molecular mechanisms controlling the pattern of alpha 4 expression. The activity of constructs containing 5' deletion mutants of the alpha 4 gene promoter was compared in transfection assays into cell lines that express alpha 4 and cell lines that do not. The sequence between position -42 and -76 base pairs (bp) was required for efficient transcription in cells that express alpha 4, but it showed no activity in HeLa cells, which do not express alpha 4. Three binding sites for the Ets family of transcription factors are found in this region: two adjacent sites at positions -50 and -54 bp and a more 5' site at position -67 bp. Using a series of constructs containing deletions and mutations in this region, we found that the 3'-most site alone was sufficient for binding GA-binding protein alpha (GABP alpha)/GABP beta and for a low level of transcriptional activation. When all three sites were present, a second complex \"a\" was detected, which contains an unknown member of the Ets family. Formation of complex a was cell-type specific and correlated with a high level of transcription. Deletion of the 5'-most Ets site had no effect on binding to GABP alpha/GABP beta, but it eliminated a. Concomitant with this loss of a, a new Ets-1-containing complex \"c\" appeared. Complex c substituted efficiently for complex a in transcriptional activation. We conclude that although neither of the two 5'-most Ets sites alone binds nuclear protein, they appear to act as modulators which control the pattern of Ets proteins that bind the alpha 4 gene promoter. This arrangement of Ets sites, coupled with the tissue- and developmental-specific expression of Ets members, likely play a key role in defining the pattern of alpha 4 integrin.\n"
],
"offsets": [
[
0,
2092
]
]
}
] | [
{
"id": "PMID-8195215_T1",
"type": "Protein",
"text": [
"alpha 4 integrin"
],
"offsets": [
[
112,
128
]
],
"normalized": []
},
{
"id": "PMID-8195215_T2",
"type": "Protein",
"text": [
"alpha 4 integrins"
],
"offsets": [
[
145,
162
]
],
"normalized": []
},
{
"id": "PMID-8195215_T3",
"type": "Protein",
"text": [
"alpha 4"
],
"offsets": [
[
402,
409
]
],
"normalized": []
},
{
"id": "PMID-8195215_T4",
"type": "Protein",
"text": [
"alpha 4"
],
"offsets": [
[
487,
494
]
],
"normalized": []
},
{
"id": "PMID-8195215_T5",
"type": "Protein",
"text": [
"alpha 4"
],
"offsets": [
[
574,
581
]
],
"normalized": []
},
{
"id": "PMID-8195215_T6",
"type": "Protein",
"text": [
"alpha 4"
],
"offsets": [
[
731,
738
]
],
"normalized": []
},
{
"id": "PMID-8195215_T7",
"type": "Protein",
"text": [
"alpha 4"
],
"offsets": [
[
802,
809
]
],
"normalized": []
},
{
"id": "PMID-8195215_T8",
"type": "Protein",
"text": [
"GA-binding protein alpha"
],
"offsets": [
[
1131,
1155
]
],
"normalized": []
},
{
"id": "PMID-8195215_T9",
"type": "Protein",
"text": [
"GABP alpha"
],
"offsets": [
[
1157,
1167
]
],
"normalized": []
},
{
"id": "PMID-8195215_T10",
"type": "Protein",
"text": [
"GABP alpha"
],
"offsets": [
[
1510,
1520
]
],
"normalized": []
},
{
"id": "PMID-8195215_T11",
"type": "Protein",
"text": [
"alpha 4"
],
"offsets": [
[
1891,
1898
]
],
"normalized": []
},
{
"id": "PMID-8195215_T12",
"type": "Protein",
"text": [
"alpha 4 integrin"
],
"offsets": [
[
2074,
2090
]
],
"normalized": []
},
{
"id": "PMID-8195215_T13",
"type": "Entity",
"text": [
"binding sites for the Ets family of transcription factors"
],
"offsets": [
[
28,
85
]
],
"normalized": []
},
{
"id": "PMID-8195215_T14",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
134,
142
]
],
"normalized": []
},
{
"id": "PMID-8195215_T15",
"type": "Entity",
"text": [
"5' deletion mutants"
],
"offsets": [
[
460,
479
]
],
"normalized": []
},
{
"id": "PMID-8195215_T16",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
500,
508
]
],
"normalized": []
},
{
"id": "PMID-8195215_T17",
"type": "Entity",
"text": [
"sequence between position -42 and -76 base pairs"
],
"offsets": [
[
614,
662
]
],
"normalized": []
},
{
"id": "PMID-8195215_T18",
"type": "Entity",
"text": [
"-42 and -76 base pairs"
],
"offsets": [
[
640,
662
]
],
"normalized": []
},
{
"id": "PMID-8195215_T19",
"type": "Entity",
"text": [
"binding sites"
],
"offsets": [
[
817,
830
]
],
"normalized": []
},
{
"id": "PMID-8195215_T20",
"type": "Entity",
"text": [
"sites at positions"
],
"offsets": [
[
914,
932
]
],
"normalized": []
},
{
"id": "PMID-8195215_T21",
"type": "Entity",
"text": [
"-50"
],
"offsets": [
[
933,
936
]
],
"normalized": []
},
{
"id": "PMID-8195215_T22",
"type": "Entity",
"text": [
"-54"
],
"offsets": [
[
941,
944
]
],
"normalized": []
},
{
"id": "PMID-8195215_T23",
"type": "Entity",
"text": [
"bp"
],
"offsets": [
[
945,
947
]
],
"normalized": []
},
{
"id": "PMID-8195215_T24",
"type": "Entity",
"text": [
"more 5' site at position -67 bp"
],
"offsets": [
[
954,
985
]
],
"normalized": []
},
{
"id": "PMID-8195215_T25",
"type": "Entity",
"text": [
"5' site"
],
"offsets": [
[
959,
966
]
],
"normalized": []
},
{
"id": "PMID-8195215_T26",
"type": "Entity",
"text": [
"-67 bp"
],
"offsets": [
[
979,
985
]
],
"normalized": []
},
{
"id": "PMID-8195215_T27",
"type": "Entity",
"text": [
"3'-most site"
],
"offsets": [
[
1085,
1097
]
],
"normalized": []
},
{
"id": "PMID-8195215_T28",
"type": "Entity",
"text": [
"/GABP beta"
],
"offsets": [
[
1168,
1178
]
],
"normalized": []
},
{
"id": "PMID-8195215_T29",
"type": "Entity",
"text": [
"complex \"a\""
],
"offsets": [
[
1274,
1285
]
],
"normalized": []
},
{
"id": "PMID-8195215_T30",
"type": "Entity",
"text": [
"complex a"
],
"offsets": [
[
1365,
1374
]
],
"normalized": []
},
{
"id": "PMID-8195215_T31",
"type": "Entity",
"text": [
"5'-most Ets site"
],
"offsets": [
[
1465,
1481
]
],
"normalized": []
},
{
"id": "PMID-8195215_T32",
"type": "Entity",
"text": [
"/GABP beta"
],
"offsets": [
[
1520,
1530
]
],
"normalized": []
},
{
"id": "PMID-8195215_T33",
"type": "Entity",
"text": [
"a"
],
"offsets": [
[
1550,
1551
]
],
"normalized": []
},
{
"id": "PMID-8195215_T34",
"type": "Entity",
"text": [
"new Ets-1-containing complex"
],
"offsets": [
[
1588,
1616
]
],
"normalized": []
},
{
"id": "PMID-8195215_T35",
"type": "Entity",
"text": [
"c"
],
"offsets": [
[
1618,
1619
]
],
"normalized": []
},
{
"id": "PMID-8195215_T36",
"type": "Entity",
"text": [
"Complex c"
],
"offsets": [
[
1631,
1640
]
],
"normalized": []
},
{
"id": "PMID-8195215_T37",
"type": "Entity",
"text": [
"complex a"
],
"offsets": [
[
1669,
1678
]
],
"normalized": []
},
{
"id": "PMID-8195215_T38",
"type": "Entity",
"text": [
"5'-most Ets sites"
],
"offsets": [
[
1755,
1772
]
],
"normalized": []
},
{
"id": "PMID-8195215_T39",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
1904,
1912
]
],
"normalized": []
},
{
"id": "PMID-8195215_T40",
"type": "Entity",
"text": [
"Ets sites"
],
"offsets": [
[
1934,
1943
]
],
"normalized": []
}
] | [] | [
{
"id": "PMID-8195215_1",
"entity_ids": [
"PMID-8195215_T8",
"PMID-8195215_T9"
]
}
] | [
{
"id": "PMID-8195215_R1",
"type": "Protein-Component",
"arg1_id": "PMID-8195215_T1",
"arg2_id": "PMID-8195215_T14",
"normalized": []
},
{
"id": "PMID-8195215_R2",
"type": "Protein-Component",
"arg1_id": "PMID-8195215_T4",
"arg2_id": "PMID-8195215_T16",
"normalized": []
},
{
"id": "PMID-8195215_R3",
"type": "Subunit-Complex",
"arg1_id": "PMID-8195215_T8",
"arg2_id": "PMID-8195215_T28",
"normalized": []
},
{
"id": "PMID-8195215_R4",
"type": "Subunit-Complex",
"arg1_id": "PMID-8195215_T10",
"arg2_id": "PMID-8195215_T32",
"normalized": []
},
{
"id": "PMID-8195215_R5",
"type": "Protein-Component",
"arg1_id": "PMID-8195215_T11",
"arg2_id": "PMID-8195215_T39",
"normalized": []
}
] |
118 | PMID-8504248 | [
{
"id": "PMID-8504248__text",
"type": "abstract",
"text": [
"Regulation of the beta-globin locus. \nTranscription of the human beta-globin gene cluster depends upon upstream regulatory sequences, which are collectively termed the locus control region. Recent studies have provided new insights into how the individual genes of the cluster are regulated through development. The crux of transcriptional activation is how the locus control region communicates with the gene-proximal regulatory elements.\n"
],
"offsets": [
[
0,
440
]
]
}
] | [
{
"id": "PMID-8504248_T1",
"type": "Protein",
"text": [
"beta-globin"
],
"offsets": [
[
18,
29
]
],
"normalized": []
},
{
"id": "PMID-8504248_T2",
"type": "Protein",
"text": [
"beta-globin"
],
"offsets": [
[
65,
76
]
],
"normalized": []
},
{
"id": "PMID-8504248_T3",
"type": "Entity",
"text": [
"locus"
],
"offsets": [
[
30,
35
]
],
"normalized": []
},
{
"id": "PMID-8504248_T4",
"type": "Entity",
"text": [
"gene cluster"
],
"offsets": [
[
77,
89
]
],
"normalized": []
},
{
"id": "PMID-8504248_T5",
"type": "Entity",
"text": [
"upstream regulatory sequences"
],
"offsets": [
[
103,
132
]
],
"normalized": []
},
{
"id": "PMID-8504248_T6",
"type": "Entity",
"text": [
"locus control region"
],
"offsets": [
[
168,
188
]
],
"normalized": []
},
{
"id": "PMID-8504248_T7",
"type": "Entity",
"text": [
"the individual genes of the cluster"
],
"offsets": [
[
241,
276
]
],
"normalized": []
},
{
"id": "PMID-8504248_T8",
"type": "Entity",
"text": [
"locus control region"
],
"offsets": [
[
362,
382
]
],
"normalized": []
},
{
"id": "PMID-8504248_T9",
"type": "Entity",
"text": [
"gene-proximal regulatory elements"
],
"offsets": [
[
405,
438
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "PMID-8504248_R1",
"type": "Protein-Component",
"arg1_id": "PMID-8504248_T2",
"arg2_id": "PMID-8504248_T6",
"normalized": []
},
{
"id": "PMID-8504248_R2",
"type": "Protein-Component",
"arg1_id": "PMID-8504248_T2",
"arg2_id": "PMID-8504248_T5",
"normalized": []
}
] |
119 | PMID-7512565 | [
{
"id": "PMID-7512565__text",
"type": "abstract",
"text": [
"Sp1 is a critical factor for the monocytic specific expression of human CD14. \nCD14 is a membrane glycoprotein expressed specifically on monocytes and macrophages, and its expression is markedly increased during the process of monocyte differentiation. In order to study CD14 gene regulation, the human CD14 gene was cloned from a partial EcoRI digested chromosome 5 library. A 5.5-kilobase genomic clone contained the full-length CD14 coding sequence and 4.2 kilobases of 5'-upstream sequence. One major and one minor transcription start site were identified 101 and 130 base pairs (bp) upstream, respectively, from the protein translation start ATG. A DNA fragment containing 128 bp of upstream sequence had strong, monocyte-specific promoter activity in the CD14 positive monocytic cell line Mono Mac 6 as compared to the nonmonocytic cell lines HeLa and REX. Four regions in this DNA fragment interact with nuclear proteins isolated from monocytic cells. The Sp1 transcription factor bound to three different regions in the CD14 promoter. Mutation of the major Sp1 binding site (-110 bp) decreased tissue-specific promoter activity, and these results, together with transactivation experiments, demonstrate that Sp1 plays a critical role in the tissue-specific expression of CD14 in monocytic cells. CD14 Sp1 site oligonucleotides bound preferentially to a 105-kDa Sp1 species, which is present in higher relative levels in monocytic than non-monocytic cells, suggesting that modification of Sp1, such as phosphorylation, may explain how the Sp1 site mediates monocytic specific promoter activity.\n"
],
"offsets": [
[
0,
1602
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}
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0,
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"CD14"
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"id": "PMID-7512565_T3",
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],
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"id": "PMID-7512565_T4",
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"id": "PMID-7512565_T5",
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"id": "PMID-7512565_T6",
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],
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"id": "PMID-7512565_T7",
"type": "Protein",
"text": [
"CD14"
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"id": "PMID-7512565_T8",
"type": "Protein",
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761,
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],
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"Sp1"
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"Sp1"
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"id": "PMID-7512565_T13",
"type": "Protein",
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"CD14"
],
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"normalized": []
},
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"id": "PMID-7512565_T14",
"type": "Protein",
"text": [
"CD14"
],
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1304,
1308
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},
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"id": "PMID-7512565_T15",
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"Sp1"
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"Sp1"
],
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},
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"id": "PMID-7512565_T18",
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"Sp1"
],
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1546,
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]
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},
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"id": "PMID-7512565_T19",
"type": "Entity",
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"4.2 kilobases of 5'-upstream sequence"
],
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[
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493
]
],
"normalized": []
},
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"id": "PMID-7512565_T20",
"type": "Entity",
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"transcription start site"
],
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519,
543
]
],
"normalized": []
},
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"id": "PMID-7512565_T21",
"type": "Entity",
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"protein translation start ATG"
],
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[
621,
650
]
],
"normalized": []
},
{
"id": "PMID-7512565_T22",
"type": "Entity",
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"promoter"
],
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[
1033,
1041
]
],
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},
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"id": "PMID-7512565_T23",
"type": "Entity",
"text": [
"binding site"
],
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[
1069,
1081
]
],
"normalized": []
},
{
"id": "PMID-7512565_T24",
"type": "Entity",
"text": [
"-110 bp"
],
"offsets": [
[
1083,
1090
]
],
"normalized": []
},
{
"id": "PMID-7512565_T25",
"type": "Entity",
"text": [
"tissue-specific promoter"
],
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[
1102,
1126
]
],
"normalized": []
},
{
"id": "PMID-7512565_T26",
"type": "Entity",
"text": [
"site oligonucleotides"
],
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[
1313,
1334
]
],
"normalized": []
},
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"id": "PMID-7512565_T27",
"type": "Entity",
"text": [
"monocytic specific promoter"
],
"offsets": [
[
1564,
1591
]
],
"normalized": []
}
] | [] | [] | [
{
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"type": "Protein-Component",
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},
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"type": "Protein-Component",
"arg1_id": "PMID-7512565_T13",
"arg2_id": "PMID-7512565_T23",
"normalized": []
}
] |
120 | PMID-9011569 | [
{
"id": "PMID-9011569__text",
"type": "abstract",
"text": [
"Glycation-dependent, reactive oxygen species-mediated suppression of the insulin gene promoter activity in HIT cells. \nProlonged poor glycemic control in non-insulin-dependent diabetes mellitus patients often leads to a decline in insulin secretion from pancreatic beta cells, accompanied by a decrease in the insulin content of the cells. As a step toward elucidating the pathophysiological background of the so-called glucose toxicity to pancreatic beta cells, we induced glycation in HIT-T15 cells using a sugar with strong deoxidizing activity, D-ribose, and examined the effects on insulin gene transcription. The results of reporter gene analyses revealed that the insulin gene promoter is more sensitive to glycation than the control beta-actin gene promoter; approximately 50 and 80% of the insulin gene promoter activity was lost when the cells were kept for 3 d in the presence of 40 and 60 mM D-ribose, respectively. In agreement with this, decrease in the insulin mRNA and insulin content was observed in the glycation-induced cells. Also, gel mobility shift analyses using specific antiserum revealed decrease in the DNA-binding activity of an insulin gene transcription factor, PDX-1/IPF1/STF-1. These effects of D-ribose seemed almost irreversible but could be prevented by addition of 1 mM aminoguanidine or 10 mM N-acetylcysteine, thus suggesting that glycation and reactive oxygen species, generated through the glycation reaction, serve as mediators of the phenomena. These observations suggest that protein glycation in pancreatic beta cells, which occurs in vivo under chronic hyperglycemia, suppresses insulin gene transcription and thus can explain part of the beta cell glucose toxicity.\n"
],
"offsets": [
[
0,
1712
]
]
}
] | [
{
"id": "PMID-9011569_T1",
"type": "Protein",
"text": [
"insulin"
],
"offsets": [
[
73,
80
]
],
"normalized": []
},
{
"id": "PMID-9011569_T2",
"type": "Protein",
"text": [
"insulin"
],
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[
158,
165
]
],
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},
{
"id": "PMID-9011569_T3",
"type": "Protein",
"text": [
"insulin"
],
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[
231,
238
]
],
"normalized": []
},
{
"id": "PMID-9011569_T4",
"type": "Protein",
"text": [
"insulin"
],
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[
587,
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]
],
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},
{
"id": "PMID-9011569_T5",
"type": "Protein",
"text": [
"insulin"
],
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[
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]
],
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},
{
"id": "PMID-9011569_T6",
"type": "Protein",
"text": [
"beta-actin"
],
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]
],
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},
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"id": "PMID-9011569_T7",
"type": "Protein",
"text": [
"insulin"
],
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]
],
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},
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"id": "PMID-9011569_T8",
"type": "Protein",
"text": [
"insulin"
],
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[
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]
],
"normalized": []
},
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"id": "PMID-9011569_T9",
"type": "Protein",
"text": [
"insulin"
],
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[
985,
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]
],
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},
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"id": "PMID-9011569_T10",
"type": "Protein",
"text": [
"insulin gene transcription factor"
],
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[
1157,
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]
],
"normalized": []
},
{
"id": "PMID-9011569_T11",
"type": "Protein",
"text": [
"PDX-1"
],
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[
1192,
1197
]
],
"normalized": []
},
{
"id": "PMID-9011569_T12",
"type": "Protein",
"text": [
"IPF1"
],
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[
1198,
1202
]
],
"normalized": []
},
{
"id": "PMID-9011569_T13",
"type": "Protein",
"text": [
"STF-1"
],
"offsets": [
[
1203,
1208
]
],
"normalized": []
},
{
"id": "PMID-9011569_T14",
"type": "Protein",
"text": [
"insulin"
],
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[
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]
],
"normalized": []
},
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"id": "PMID-9011569_T15",
"type": "Entity",
"text": [
"promoter"
],
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[
86,
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]
],
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},
{
"id": "PMID-9011569_T16",
"type": "Entity",
"text": [
"reporter gene"
],
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[
630,
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]
],
"normalized": []
},
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"id": "PMID-9011569_T17",
"type": "Entity",
"text": [
"promoter"
],
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684,
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]
],
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},
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"id": "PMID-9011569_T18",
"type": "Entity",
"text": [
"promoter"
],
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[
757,
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]
],
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},
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"id": "PMID-9011569_T19",
"type": "Entity",
"text": [
"promoter"
],
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[
812,
820
]
],
"normalized": []
},
{
"id": "PMID-9011569_T20",
"type": "Entity",
"text": [
"N-acetylcysteine"
],
"offsets": [
[
1330,
1346
]
],
"normalized": []
}
] | [] | [
{
"id": "PMID-9011569_1",
"entity_ids": [
"PMID-9011569_T10",
"PMID-9011569_T11",
"PMID-9011569_T12",
"PMID-9011569_T13"
]
}
] | [
{
"id": "PMID-9011569_R1",
"type": "Protein-Component",
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"arg2_id": "PMID-9011569_T15",
"normalized": []
},
{
"id": "PMID-9011569_R2",
"type": "Protein-Component",
"arg1_id": "PMID-9011569_T5",
"arg2_id": "PMID-9011569_T17",
"normalized": []
},
{
"id": "PMID-9011569_R3",
"type": "Protein-Component",
"arg1_id": "PMID-9011569_T6",
"arg2_id": "PMID-9011569_T18",
"normalized": []
},
{
"id": "PMID-9011569_R4",
"type": "Protein-Component",
"arg1_id": "PMID-9011569_T7",
"arg2_id": "PMID-9011569_T19",
"normalized": []
}
] |
121 | PMID-9231664 | [
{
"id": "PMID-9231664__text",
"type": "abstract",
"text": [
"Pancreatic islet expression studies and polymorphic DNA markers in the genes encoding hepatocyte nuclear factor-3alpha, -3beta, -3gamma, -4gamma, and -6. \nThe genes encoding the functionally related hepatocyte nuclear factors HNF-1alpha and HNF-4alpha play a critical role in normal pancreatic beta-cell function. Mutations in these liver-enriched transcription factors result in two forms of early-onset type 2 diabetes (maturity-onset diabetes of the young [MODY]), MODY3 and MODY1, which are characterized by impaired glucose-stimulated insulin secretion, early disease onset, and autosomal dominant inheritance. The transcriptional hierarchy of HNFs suggests that other proteins of the regulatory cascade might be responsible for other forms of MODY and/or late-onset type 2 diabetes. In this study, we show that HNF-3alpha, -3beta, -3gamma, -4gamma, and -6 are expressed in pancreatic beta-cells. We report the identification and characterization of simple tandem repeat DNA polymorphisms in the genes encoding HNF-3alpha, -3beta, -3gamma, -4gamma, and -6 and the mapping of HNF-6 to chromosome bands 15q21.1-21.2 by fluorescence in situ hybridization. These markers will be useful to study the role of genetic variation in these genes in the pathogenesis of type 2 diabetes.\n"
],
"offsets": [
[
0,
1281
]
]
}
] | [
{
"id": "PMID-9231664_T1",
"type": "Protein",
"text": [
"hepatocyte nuclear factor-3alpha"
],
"offsets": [
[
86,
118
]
],
"normalized": []
},
{
"id": "PMID-9231664_T2",
"type": "Protein",
"text": [
"-3beta"
],
"offsets": [
[
120,
126
]
],
"normalized": []
},
{
"id": "PMID-9231664_T3",
"type": "Protein",
"text": [
"-3gamma"
],
"offsets": [
[
128,
135
]
],
"normalized": []
},
{
"id": "PMID-9231664_T4",
"type": "Protein",
"text": [
"-4gamma"
],
"offsets": [
[
137,
144
]
],
"normalized": []
},
{
"id": "PMID-9231664_T5",
"type": "Protein",
"text": [
"-6"
],
"offsets": [
[
150,
152
]
],
"normalized": []
},
{
"id": "PMID-9231664_T6",
"type": "Protein",
"text": [
"HNF-1alpha"
],
"offsets": [
[
226,
236
]
],
"normalized": []
},
{
"id": "PMID-9231664_T7",
"type": "Protein",
"text": [
"HNF-4alpha"
],
"offsets": [
[
241,
251
]
],
"normalized": []
},
{
"id": "PMID-9231664_T8",
"type": "Protein",
"text": [
"HNF-3alpha"
],
"offsets": [
[
817,
827
]
],
"normalized": []
},
{
"id": "PMID-9231664_T9",
"type": "Protein",
"text": [
"-3beta"
],
"offsets": [
[
829,
835
]
],
"normalized": []
},
{
"id": "PMID-9231664_T10",
"type": "Protein",
"text": [
"-3gamma"
],
"offsets": [
[
837,
844
]
],
"normalized": []
},
{
"id": "PMID-9231664_T11",
"type": "Protein",
"text": [
"-4gamma"
],
"offsets": [
[
846,
853
]
],
"normalized": []
},
{
"id": "PMID-9231664_T12",
"type": "Protein",
"text": [
"-6"
],
"offsets": [
[
859,
861
]
],
"normalized": []
},
{
"id": "PMID-9231664_T13",
"type": "Protein",
"text": [
"HNF-3alpha"
],
"offsets": [
[
1016,
1026
]
],
"normalized": []
},
{
"id": "PMID-9231664_T14",
"type": "Protein",
"text": [
"-3beta"
],
"offsets": [
[
1028,
1034
]
],
"normalized": []
},
{
"id": "PMID-9231664_T15",
"type": "Protein",
"text": [
"-3gamma"
],
"offsets": [
[
1036,
1043
]
],
"normalized": []
},
{
"id": "PMID-9231664_T16",
"type": "Protein",
"text": [
"-4gamma"
],
"offsets": [
[
1045,
1052
]
],
"normalized": []
},
{
"id": "PMID-9231664_T17",
"type": "Protein",
"text": [
"-6"
],
"offsets": [
[
1058,
1060
]
],
"normalized": []
},
{
"id": "PMID-9231664_T18",
"type": "Protein",
"text": [
"HNF-6"
],
"offsets": [
[
1080,
1085
]
],
"normalized": []
},
{
"id": "PMID-9231664_T19",
"type": "Entity",
"text": [
"The genes encoding"
],
"offsets": [
[
155,
173
]
],
"normalized": []
},
{
"id": "PMID-9231664_T20",
"type": "Entity",
"text": [
"liver-enriched transcription factors"
],
"offsets": [
[
333,
369
]
],
"normalized": []
},
{
"id": "PMID-9231664_T21",
"type": "Entity",
"text": [
"simple tandem repeat DNA"
],
"offsets": [
[
955,
979
]
],
"normalized": []
},
{
"id": "PMID-9231664_T22",
"type": "Entity",
"text": [
"chromosome bands"
],
"offsets": [
[
1089,
1105
]
],
"normalized": []
},
{
"id": "PMID-9231664_T23",
"type": "Entity",
"text": [
"15q21.1-21.2"
],
"offsets": [
[
1106,
1118
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "PMID-9231664_R1",
"type": "Protein-Component",
"arg1_id": "PMID-9231664_T14",
"arg2_id": "PMID-9231664_T21",
"normalized": []
},
{
"id": "PMID-9231664_R2",
"type": "Protein-Component",
"arg1_id": "PMID-9231664_T15",
"arg2_id": "PMID-9231664_T21",
"normalized": []
},
{
"id": "PMID-9231664_R3",
"type": "Protein-Component",
"arg1_id": "PMID-9231664_T13",
"arg2_id": "PMID-9231664_T21",
"normalized": []
}
] |
122 | PMID-9052735 | [
{
"id": "PMID-9052735__text",
"type": "abstract",
"text": [
"A negative regulatory region containing a glucocorticosteroid response element (nGRE) in the human interleukin-1beta gene. \nInterleukin-1 beta (IL-1beta) is one of the most important inflammatory mediators in human inflammatory and immunological diseases. The regulation of human IL-1beta gene expression has been studied for several years, and a few regulatory elements have been discovered in the promoter region. However, little is known about negative regulation of IL-1beta expression at the transcriptional level, which may play an important role in anti-inflammatory and immunosuppressive effects. We have identified a negative regulatory element located in the region between -685 and -395. Within this region, a 19-bp nuclear factor binding site (-570 to -552) was characterized by DNase I footprinting and electromobility shift assay. A consensus sequence for a negative glucocorticoid response element (nGRE) and a transcription activator protein-2 binding site were noted within this footprint. Functional studies showed a 2.5-fold increase in promoter activity when this 19-bp binding site was deleted in the reporter constructs IL-1beta/CAT and IL-1beta/SV40 promoter/CAT. Dexamethasone (10(-8) M) repressed chloramphenicol acetyltransferase (CAT) production by 75% in the wild-type fragment but not in a deletion mutant lacking the 19-bp site. A protein of about 150 kD that bound to this negative regulatory sequence was identified by UV cross-linking. This is the first description of a negative regulatory region responsive to glucocorticoids in a cytokine gene.\n"
],
"offsets": [
[
0,
1581
]
]
}
] | [
{
"id": "PMID-9052735_T1",
"type": "Protein",
"text": [
"interleukin-1beta"
],
"offsets": [
[
99,
116
]
],
"normalized": []
},
{
"id": "PMID-9052735_T2",
"type": "Protein",
"text": [
"Interleukin-1 beta"
],
"offsets": [
[
124,
142
]
],
"normalized": []
},
{
"id": "PMID-9052735_T3",
"type": "Protein",
"text": [
"IL-1beta"
],
"offsets": [
[
144,
152
]
],
"normalized": []
},
{
"id": "PMID-9052735_T4",
"type": "Protein",
"text": [
"IL-1beta"
],
"offsets": [
[
280,
288
]
],
"normalized": []
},
{
"id": "PMID-9052735_T5",
"type": "Protein",
"text": [
"IL-1beta"
],
"offsets": [
[
470,
478
]
],
"normalized": []
},
{
"id": "PMID-9052735_T6",
"type": "Protein",
"text": [
"transcription activator protein-2"
],
"offsets": [
[
926,
959
]
],
"normalized": []
},
{
"id": "PMID-9052735_T7",
"type": "Protein",
"text": [
"IL-1beta"
],
"offsets": [
[
1142,
1150
]
],
"normalized": []
},
{
"id": "PMID-9052735_T8",
"type": "Protein",
"text": [
"CAT"
],
"offsets": [
[
1151,
1154
]
],
"normalized": []
},
{
"id": "PMID-9052735_T9",
"type": "Protein",
"text": [
"IL-1beta"
],
"offsets": [
[
1159,
1167
]
],
"normalized": []
},
{
"id": "PMID-9052735_T10",
"type": "Protein",
"text": [
"CAT"
],
"offsets": [
[
1182,
1185
]
],
"normalized": []
},
{
"id": "PMID-9052735_T11",
"type": "Protein",
"text": [
"chloramphenicol acetyltransferase"
],
"offsets": [
[
1222,
1255
]
],
"normalized": []
},
{
"id": "PMID-9052735_T12",
"type": "Protein",
"text": [
"CAT"
],
"offsets": [
[
1257,
1260
]
],
"normalized": []
},
{
"id": "PMID-9052735_T13",
"type": "Entity",
"text": [
"nGRE"
],
"offsets": [
[
80,
84
]
],
"normalized": []
},
{
"id": "PMID-9052735_T14",
"type": "Entity",
"text": [
"regulatory elements"
],
"offsets": [
[
351,
370
]
],
"normalized": []
},
{
"id": "PMID-9052735_T15",
"type": "Entity",
"text": [
"promoter region"
],
"offsets": [
[
399,
414
]
],
"normalized": []
},
{
"id": "PMID-9052735_T16",
"type": "Entity",
"text": [
"negative regulatory element"
],
"offsets": [
[
626,
653
]
],
"normalized": []
},
{
"id": "PMID-9052735_T17",
"type": "Entity",
"text": [
"-685 and -395"
],
"offsets": [
[
684,
697
]
],
"normalized": []
},
{
"id": "PMID-9052735_T18",
"type": "Entity",
"text": [
"19-bp nuclear factor binding site"
],
"offsets": [
[
721,
754
]
],
"normalized": []
},
{
"id": "PMID-9052735_T19",
"type": "Entity",
"text": [
"-570 to -552"
],
"offsets": [
[
756,
768
]
],
"normalized": []
},
{
"id": "PMID-9052735_T20",
"type": "Entity",
"text": [
"consensus sequence"
],
"offsets": [
[
847,
865
]
],
"normalized": []
},
{
"id": "PMID-9052735_T21",
"type": "Entity",
"text": [
"negative glucocorticoid response element"
],
"offsets": [
[
872,
912
]
],
"normalized": []
},
{
"id": "PMID-9052735_T22",
"type": "Entity",
"text": [
"nGRE"
],
"offsets": [
[
914,
918
]
],
"normalized": []
},
{
"id": "PMID-9052735_T23",
"type": "Entity",
"text": [
"binding site"
],
"offsets": [
[
960,
972
]
],
"normalized": []
},
{
"id": "PMID-9052735_T24",
"type": "Entity",
"text": [
"19-bp binding site"
],
"offsets": [
[
1084,
1102
]
],
"normalized": []
},
{
"id": "PMID-9052735_T25",
"type": "Entity",
"text": [
"reporter constructs"
],
"offsets": [
[
1122,
1141
]
],
"normalized": []
},
{
"id": "PMID-9052735_T26",
"type": "Entity",
"text": [
"SV40 promoter"
],
"offsets": [
[
1168,
1181
]
],
"normalized": []
},
{
"id": "PMID-9052735_T27",
"type": "Entity",
"text": [
"wild-type fragment"
],
"offsets": [
[
1287,
1305
]
],
"normalized": []
},
{
"id": "PMID-9052735_T28",
"type": "Entity",
"text": [
"deletion mutant"
],
"offsets": [
[
1319,
1334
]
],
"normalized": []
},
{
"id": "PMID-9052735_T29",
"type": "Entity",
"text": [
"19-bp site"
],
"offsets": [
[
1347,
1357
]
],
"normalized": []
},
{
"id": "PMID-9052735_T30",
"type": "Entity",
"text": [
"negative regulatory sequence"
],
"offsets": [
[
1404,
1432
]
],
"normalized": []
},
{
"id": "PMID-9052735_T31",
"type": "Entity",
"text": [
"negative regulatory region"
],
"offsets": [
[
1504,
1530
]
],
"normalized": []
},
{
"id": "PMID-9052735_T32",
"type": "Entity",
"text": [
"cytokine gene"
],
"offsets": [
[
1566,
1579
]
],
"normalized": []
}
] | [] | [
{
"id": "PMID-9052735_1",
"entity_ids": [
"PMID-9052735_T2",
"PMID-9052735_T3"
]
},
{
"id": "PMID-9052735_2",
"entity_ids": [
"PMID-9052735_T11",
"PMID-9052735_T12"
]
}
] | [] |
123 | PMID-1656391 | [
{
"id": "PMID-1656391__text",
"type": "abstract",
"text": [
"An erythroid specific enhancer upstream to the gene encoding the cell-type specific transcription factor GATA-1. \nThe transcription factor GATA-1 is expressed in a subset of hemopoietic cells, where it mediates the cell-type specific expression of several genes. We have cloned the mouse and human GATA-1 genes. A region upstream to the first exon, and highly conserved between mouse and man, acts as an erythroid specific enhancer in transient assays, if linked to the GATA-1 or to the SV40 promoter. The activity of the enhancer is almost completely dependent on the integrity of a dimeric GATA-1 binding site.\n"
],
"offsets": [
[
0,
613
]
]
}
] | [
{
"id": "PMID-1656391_T1",
"type": "Protein",
"text": [
"GATA-1"
],
"offsets": [
[
105,
111
]
],
"normalized": []
},
{
"id": "PMID-1656391_T2",
"type": "Protein",
"text": [
"GATA-1"
],
"offsets": [
[
139,
145
]
],
"normalized": []
},
{
"id": "PMID-1656391_T3",
"type": "Protein",
"text": [
"GATA-1"
],
"offsets": [
[
470,
476
]
],
"normalized": []
},
{
"id": "PMID-1656391_T4",
"type": "Protein",
"text": [
"GATA-1"
],
"offsets": [
[
592,
598
]
],
"normalized": []
},
{
"id": "PMID-1656391_T5",
"type": "Entity",
"text": [
"erythroid specific enhancer"
],
"offsets": [
[
3,
30
]
],
"normalized": []
},
{
"id": "PMID-1656391_T6",
"type": "Entity",
"text": [
"several genes"
],
"offsets": [
[
248,
261
]
],
"normalized": []
},
{
"id": "PMID-1656391_T7",
"type": "Entity",
"text": [
"GATA-1 genes"
],
"offsets": [
[
298,
310
]
],
"normalized": []
},
{
"id": "PMID-1656391_T8",
"type": "Entity",
"text": [
"region upstream"
],
"offsets": [
[
314,
329
]
],
"normalized": []
},
{
"id": "PMID-1656391_T9",
"type": "Entity",
"text": [
"erythroid specific enhancer"
],
"offsets": [
[
404,
431
]
],
"normalized": []
},
{
"id": "PMID-1656391_T10",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
492,
500
]
],
"normalized": []
},
{
"id": "PMID-1656391_T11",
"type": "Entity",
"text": [
"dimeric GATA-1"
],
"offsets": [
[
584,
598
]
],
"normalized": []
},
{
"id": "PMID-1656391_T12",
"type": "Entity",
"text": [
"binding site"
],
"offsets": [
[
599,
611
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "PMID-1656391_R1",
"type": "Protein-Component",
"arg1_id": "PMID-1656391_T1",
"arg2_id": "PMID-1656391_T5",
"normalized": []
},
{
"id": "PMID-1656391_R2",
"type": "Protein-Component",
"arg1_id": "PMID-1656391_T3",
"arg2_id": "PMID-1656391_T10",
"normalized": []
},
{
"id": "PMID-1656391_R3",
"type": "Subunit-Complex",
"arg1_id": "PMID-1656391_T4",
"arg2_id": "PMID-1656391_T11",
"normalized": []
}
] |
124 | PMID-1583734 | [
{
"id": "PMID-1583734__text",
"type": "abstract",
"text": [
"Specific NF-kappa B subunits act in concert with Tat to stimulate human immunodeficiency virus type 1 transcription. \nNF-kappa B is a protein complex which functions in concert with the tat-I gene product to stimulate human immunodeficiency virus (HIV) transcription. To determine whether specific members of the NF-kappa B family contribute to this effect, we have examined the abilities of different NF-kappa B subunits to act with Tat-I to stimulate transcription of HIV in Jurkat T-leukemia cells. We have found that the p49(100) DNA binding subunit, together with p65, can act in concert with Tat-I to stimulate the expression of HIV-CAT plasmid. Little effect was observed with 50-kDa forms of p105 NF-kappa B or rel, in combination with p65 or full-length c-rel, which do not stimulate the HIV enhancer in these cells. These findings suggest that the combination of p49(100) and p65 NF-kappa B can act in concert with the tat-I gene product to stimulate the synthesis of HIV RNA.\n"
],
"offsets": [
[
0,
987
]
]
}
] | [
{
"id": "PMID-1583734_T1",
"type": "Protein",
"text": [
"Tat"
],
"offsets": [
[
49,
52
]
],
"normalized": []
},
{
"id": "PMID-1583734_T2",
"type": "Protein",
"text": [
"tat-I"
],
"offsets": [
[
186,
191
]
],
"normalized": []
},
{
"id": "PMID-1583734_T3",
"type": "Protein",
"text": [
"Tat-I"
],
"offsets": [
[
434,
439
]
],
"normalized": []
},
{
"id": "PMID-1583734_T4",
"type": "Protein",
"text": [
"p49(100)"
],
"offsets": [
[
525,
533
]
],
"normalized": []
},
{
"id": "PMID-1583734_T5",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
569,
572
]
],
"normalized": []
},
{
"id": "PMID-1583734_T6",
"type": "Protein",
"text": [
"Tat-I"
],
"offsets": [
[
598,
603
]
],
"normalized": []
},
{
"id": "PMID-1583734_T7",
"type": "Protein",
"text": [
"CAT"
],
"offsets": [
[
639,
642
]
],
"normalized": []
},
{
"id": "PMID-1583734_T8",
"type": "Protein",
"text": [
"p105"
],
"offsets": [
[
700,
704
]
],
"normalized": []
},
{
"id": "PMID-1583734_T9",
"type": "Protein",
"text": [
"rel"
],
"offsets": [
[
719,
722
]
],
"normalized": []
},
{
"id": "PMID-1583734_T10",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
744,
747
]
],
"normalized": []
},
{
"id": "PMID-1583734_T11",
"type": "Protein",
"text": [
"c-rel"
],
"offsets": [
[
763,
768
]
],
"normalized": []
},
{
"id": "PMID-1583734_T12",
"type": "Protein",
"text": [
"p49(100)"
],
"offsets": [
[
873,
881
]
],
"normalized": []
},
{
"id": "PMID-1583734_T13",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
886,
889
]
],
"normalized": []
},
{
"id": "PMID-1583734_T14",
"type": "Protein",
"text": [
"tat-I"
],
"offsets": [
[
929,
934
]
],
"normalized": []
},
{
"id": "PMID-1583734_T15",
"type": "Entity",
"text": [
"NF-kappa B"
],
"offsets": [
[
9,
19
]
],
"normalized": []
},
{
"id": "PMID-1583734_T16",
"type": "Entity",
"text": [
"NF-kappa B"
],
"offsets": [
[
118,
128
]
],
"normalized": []
},
{
"id": "PMID-1583734_T17",
"type": "Entity",
"text": [
"NF-kappa B"
],
"offsets": [
[
402,
412
]
],
"normalized": []
},
{
"id": "PMID-1583734_T18",
"type": "Entity",
"text": [
"DNA"
],
"offsets": [
[
534,
537
]
],
"normalized": []
},
{
"id": "PMID-1583734_T19",
"type": "Entity",
"text": [
"HIV enhancer"
],
"offsets": [
[
797,
809
]
],
"normalized": []
}
] | [] | [] | [] |
125 | PMID-7540942 | [
{
"id": "PMID-7540942__text",
"type": "abstract",
"text": [
"Cross-linking of CD30 induces HIV expression in chronically infected T cells. \nCD30, a member of the tumor necrosis factor (TNF) receptor family, is expressed constitutively on the surface of the human T cell line ACH-2, which is chronically infected with human immunodeficiency virus type-1 (HIV)-1. We demonstrate that cross-linking CD30 with an anti-CD30-specific monoclonal antibody, which mimics the described biological activities of the CD30 ligand (CD30L), results in HIV expression. CD30 cross-linking does not alter proliferation of ACH-2 cells and the induction of HIV expression is not mediated by endogenous TNF alpha/beta. Furthermore, cross-linking of CD30 leads to NF-kappa B activation and enhanced HIV transcription. Thus, CD30-CD30L interactions mediate the induction of HIV expression by a kappa B-dependent pathway that is independent of TNF. This mechanism may be important in the activation of HIV expression from latently infected CD4+ T cells, especially in lymphoid organs where cell to cell contact is conducive to receptor-ligand interactions.\n"
],
"offsets": [
[
0,
1072
]
]
}
] | [
{
"id": "PMID-7540942_T1",
"type": "Protein",
"text": [
"CD30"
],
"offsets": [
[
17,
21
]
],
"normalized": []
},
{
"id": "PMID-7540942_T2",
"type": "Protein",
"text": [
"CD30"
],
"offsets": [
[
79,
83
]
],
"normalized": []
},
{
"id": "PMID-7540942_T3",
"type": "Protein",
"text": [
"CD30"
],
"offsets": [
[
335,
339
]
],
"normalized": []
},
{
"id": "PMID-7540942_T4",
"type": "Protein",
"text": [
"CD30"
],
"offsets": [
[
353,
357
]
],
"normalized": []
},
{
"id": "PMID-7540942_T5",
"type": "Protein",
"text": [
"CD30 ligand"
],
"offsets": [
[
444,
455
]
],
"normalized": []
},
{
"id": "PMID-7540942_T6",
"type": "Protein",
"text": [
"CD30L"
],
"offsets": [
[
457,
462
]
],
"normalized": []
},
{
"id": "PMID-7540942_T7",
"type": "Protein",
"text": [
"CD30"
],
"offsets": [
[
492,
496
]
],
"normalized": []
},
{
"id": "PMID-7540942_T8",
"type": "Protein",
"text": [
"TNF alpha"
],
"offsets": [
[
621,
630
]
],
"normalized": []
},
{
"id": "PMID-7540942_T9",
"type": "Protein",
"text": [
"beta"
],
"offsets": [
[
631,
635
]
],
"normalized": []
},
{
"id": "PMID-7540942_T10",
"type": "Protein",
"text": [
"CD30"
],
"offsets": [
[
667,
671
]
],
"normalized": []
},
{
"id": "PMID-7540942_T11",
"type": "Protein",
"text": [
"CD30"
],
"offsets": [
[
741,
745
]
],
"normalized": []
},
{
"id": "PMID-7540942_T12",
"type": "Protein",
"text": [
"CD30L"
],
"offsets": [
[
746,
751
]
],
"normalized": []
},
{
"id": "PMID-7540942_T13",
"type": "Protein",
"text": [
"CD4"
],
"offsets": [
[
955,
958
]
],
"normalized": []
},
{
"id": "PMID-7540942_T14",
"type": "Entity",
"text": [
"NF-kappa B"
],
"offsets": [
[
681,
691
]
],
"normalized": []
},
{
"id": "PMID-7540942_T15",
"type": "Entity",
"text": [
"kappa B"
],
"offsets": [
[
810,
817
]
],
"normalized": []
}
] | [] | [
{
"id": "PMID-7540942_1",
"entity_ids": [
"PMID-7540942_T5",
"PMID-7540942_T6"
]
}
] | [] |
126 | PMID-10369255 | [
{
"id": "PMID-10369255__text",
"type": "abstract",
"text": [
"A polymorphism that affects OCT-1 binding to the TNF promoter region is associated with severe malaria [see comments] \nGenetic variation in cytokine promoter regions is postulated to influence susceptibility to infection, but the molecular mechanisms by which such polymorphisms might affect gene regulation are unknown. Through systematic DNA footprinting of the TNF (encoding tumour necrosis factor, TNF) promoter region, we have identified a single nucleotide polymorphism (SNP) that causes the helix-turn-helix transcription factor OCT-1 to bind to a novel region of complex protein-DNA interactions and alters gene expression in human monocytes. The OCT-1-binding genotype, found in approximately 5% of Africans, is associated with fourfold increased susceptibility to cerebral malaria in large case-control studies of West African and East African populations, after correction for other known TNF polymorphisms and linked HLA alleles.\n"
],
"offsets": [
[
0,
942
]
]
}
] | [
{
"id": "PMID-10369255_T1",
"type": "Protein",
"text": [
"OCT-1"
],
"offsets": [
[
28,
33
]
],
"normalized": []
},
{
"id": "PMID-10369255_T2",
"type": "Protein",
"text": [
"TNF"
],
"offsets": [
[
49,
52
]
],
"normalized": []
},
{
"id": "PMID-10369255_T3",
"type": "Protein",
"text": [
"TNF"
],
"offsets": [
[
364,
367
]
],
"normalized": []
},
{
"id": "PMID-10369255_T4",
"type": "Protein",
"text": [
"tumour necrosis factor"
],
"offsets": [
[
378,
400
]
],
"normalized": []
},
{
"id": "PMID-10369255_T5",
"type": "Protein",
"text": [
"TNF"
],
"offsets": [
[
402,
405
]
],
"normalized": []
},
{
"id": "PMID-10369255_T6",
"type": "Protein",
"text": [
"OCT-1"
],
"offsets": [
[
536,
541
]
],
"normalized": []
},
{
"id": "PMID-10369255_T7",
"type": "Protein",
"text": [
"OCT-1"
],
"offsets": [
[
655,
660
]
],
"normalized": []
},
{
"id": "PMID-10369255_T8",
"type": "Protein",
"text": [
"TNF"
],
"offsets": [
[
900,
903
]
],
"normalized": []
},
{
"id": "PMID-10369255_T9",
"type": "Entity",
"text": [
"promoter region"
],
"offsets": [
[
53,
68
]
],
"normalized": []
},
{
"id": "PMID-10369255_T10",
"type": "Entity",
"text": [
"cytokine promoter regions"
],
"offsets": [
[
140,
165
]
],
"normalized": []
},
{
"id": "PMID-10369255_T11",
"type": "Entity",
"text": [
"promoter region"
],
"offsets": [
[
407,
422
]
],
"normalized": []
},
{
"id": "PMID-10369255_T12",
"type": "Entity",
"text": [
"helix-turn-helix"
],
"offsets": [
[
498,
514
]
],
"normalized": []
},
{
"id": "PMID-10369255_T13",
"type": "Entity",
"text": [
"novel region"
],
"offsets": [
[
555,
567
]
],
"normalized": []
},
{
"id": "PMID-10369255_T14",
"type": "Entity",
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"complex protein"
],
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[
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"id": "PMID-10369255_T15",
"type": "Entity",
"text": [
"DNA"
],
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587,
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"id": "PMID-10369255_T16",
"type": "Entity",
"text": [
"HLA alleles"
],
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[
929,
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],
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] | [] | [
{
"id": "PMID-10369255_1",
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"PMID-10369255_T4",
"PMID-10369255_T5"
]
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}
] |
127 | PMID-9915779 | [
{
"id": "PMID-9915779__text",
"type": "abstract",
"text": [
"Anoxia/reoxygenation-induced tolerance with respect to polymorphonuclear leukocyte adhesion to cultured endothelial cells. A nuclear factor-kappaB-mediated phenomenon. \nExposing human umbilical vein endothelial cells (HUVECs) to anoxia/reoxygenation (A/R) results in an increase in polymorphonuclear leukocyte (PMN) adhesion to HUVECs. This A/R-induced hyperadhesion is completely prevented by a previous (24 hours earlier) exposure of HUVECs to A/R. This phenomenon has been termed \"A/R tolerance.\" Exposing HUVECs to A/R induces an increase in nuclear factor kappaB (NF-kappaB) in HUVEC nuclei within 4 hours. Interfering with either NF-kappaB activation (proteasome inhibitor) or translocation (double-stranded oligonucleotides containing NF-kappaB binding sequence) prevents the development of A/R tolerance (ie, the increase in A/R-induced PMN adhesion to HUVECs is the same after the first and second A/R challenges). NO production by HUVECs is increased after the second A/R challenge, but not after the first A/R challenge. Inhibition of NO synthase (NOS) during the second A/R challenge prevents the development of A/R tolerance with respect to PMN adhesion. However, while HUVECs contained endothelial NOS protein, no inducible NOS was detected in either tolerant or nontolerant cells. Further studies indicated that inhibition of GTP-cyclohydrolase I (an enzyme involved in de novo synthesis of an important cofactor for NOS activity, tetrahydrobiopterin) prevented the generation of NO in A/R-tolerant cells. Extracellular generation of NO (NO donor) did not effect the hyperadhesion response induced by the initial A/R challenge. A/R also induced an oxidant stress in naive HUVECs, but not in A/R-tolerant HUVECs. Inhibition of NOS during the second A/R insult results in the generation of an oxidant stress similar to that observed after the first A/R challenge. Taken together, the findings of the present study are consistent with a role for NF-kappaB in the development of A/R tolerance (with respect to PMN adhesion), perhaps by transcriptional regulation of GTP-cyclohydrolase. The increased NO production during the second A/R insult reduces PMN adhesion most likely by reducing the intracellular oxidant stress induced by A/R.\n"
],
"offsets": [
[
0,
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]
]
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] | [
{
"id": "PMID-9915779_T1",
"type": "Protein",
"text": [
"NO synthase"
],
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"id": "PMID-9915779_T2",
"type": "Protein",
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"NOS"
],
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"id": "PMID-9915779_T3",
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"NOS"
],
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"id": "PMID-9915779_T4",
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"id": "PMID-9915779_T5",
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"GTP-cyclohydrolase I"
],
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"id": "PMID-9915779_T6",
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"id": "PMID-9915779_T7",
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"NOS"
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"id": "PMID-9915779_T8",
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"GTP-cyclohydrolase"
],
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"id": "PMID-9915779_T9",
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"nuclear factor-kappaB"
],
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125,
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]
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"id": "PMID-9915779_T10",
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"nuclear factor kappaB"
],
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],
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"id": "PMID-9915779_T11",
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"id": "PMID-9915779_T12",
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"NF-kappaB"
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"id": "PMID-9915779_T13",
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"proteasome"
],
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658,
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]
],
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},
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"id": "PMID-9915779_T14",
"type": "Entity",
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"double-stranded oligonucleotides"
],
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698,
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],
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"id": "PMID-9915779_T15",
"type": "Entity",
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"NF-kappaB binding sequence"
],
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"id": "PMID-9915779_T16",
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"NF-kappaB"
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"id": "PMID-9915779_T17",
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"NF-kappaB"
],
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}
] | [] | [
{
"id": "PMID-9915779_1",
"entity_ids": [
"PMID-9915779_T1",
"PMID-9915779_T2"
]
}
] | [] |
128 | PMID-2006151 | [
{
"id": "PMID-2006151__text",
"type": "abstract",
"text": [
"Comparison of constitutive and inducible transcriptional enhancement mediated by kappa B-related sequences: modulation of activity in B cells by human T-cell leukemia virus type I tax gene. \nThe kappa B sequence (GGGACTTTCC) binds a factor, NF-kappa B, that is constitutively found in its functional, DNA binding form only in B lymphocytes. A factor with apparently indistinguishable sequence specificity can be induced in many other cell types, where it is used to regulate inducible gene expression. For example, kappa B-related sequences have been shown to be important for the transcription of a few inducible genes, such as the interleukin 2 receptor alpha-chain gene and the beta-interferon gene. However, these genes are not constitutively active in B lymphocytes, suggesting that other regulatory mechanisms must play a role in determining the patterns of expression. We have investigated the constitutive and inducible transcriptional activity mediated by five kappa B-related sequence elements in two different cell types. We show that in S194 plasma cells the activity of each element correlates well with the relative affinity of B-cell-derived NF-kappa B for that element. This leads to significantly lower transcription enhancement by sites derived from the interleukin 2 receptor or T-cell receptor genes in S194 cells. However, in either EL-4 (T) cells or S194 cells, both lower-affinity sites can be significantly induced by the tax gene product of human T-cell leukemia virus type I, showing that NF-kappa B activity can be modulated even in a B-cell line that constitutively expresses this factor.\n"
],
"offsets": [
[
0,
1617
]
]
}
] | [
{
"id": "PMID-2006151_T1",
"type": "Protein",
"text": [
"tax"
],
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[
180,
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]
],
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},
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"id": "PMID-2006151_T2",
"type": "Protein",
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"interleukin 2 receptor alpha-chain"
],
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633,
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]
],
"normalized": []
},
{
"id": "PMID-2006151_T3",
"type": "Protein",
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"beta-interferon"
],
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[
681,
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]
],
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},
{
"id": "PMID-2006151_T4",
"type": "Protein",
"text": [
"tax"
],
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1446,
1449
]
],
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},
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"id": "PMID-2006151_T5",
"type": "Entity",
"text": [
"kappa B-related sequences"
],
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[
81,
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]
],
"normalized": []
},
{
"id": "PMID-2006151_T6",
"type": "Entity",
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"kappa B sequence"
],
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195,
211
]
],
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},
{
"id": "PMID-2006151_T7",
"type": "Entity",
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"GGGACTTTCC"
],
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213,
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]
],
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},
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"id": "PMID-2006151_T8",
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"NF-kappa B"
],
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241,
251
]
],
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},
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"id": "PMID-2006151_T9",
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"kappa B-related sequences"
],
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515,
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]
],
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},
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"id": "PMID-2006151_T10",
"type": "Entity",
"text": [
"inducible genes"
],
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[
604,
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]
],
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},
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"id": "PMID-2006151_T11",
"type": "Entity",
"text": [
"kappa B-related sequence elements"
],
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],
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},
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"id": "PMID-2006151_T12",
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],
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]
],
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},
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"id": "PMID-2006151_T13",
"type": "Entity",
"text": [
"sites derived from"
],
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1249,
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],
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},
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"id": "PMID-2006151_T14",
"type": "Entity",
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"interleukin 2 receptor"
],
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1272,
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],
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},
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"id": "PMID-2006151_T15",
"type": "Entity",
"text": [
"T-cell receptor genes"
],
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1298,
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]
],
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},
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"id": "PMID-2006151_T16",
"type": "Entity",
"text": [
"NF-kappa B"
],
"offsets": [
[
1515,
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]
],
"normalized": []
}
] | [] | [] | [] |
129 | PMID-9199300 | [
{
"id": "PMID-9199300__text",
"type": "abstract",
"text": [
"Comparison of the transactivation domains of Stat5 and Stat6 in lymphoid cells and mammary epithelial cells. \nStat (signal transducers and activators of transcription) and Jak (Janus kinases) proteins are central components in the signal transduction events in hematopoietic and epithelial cells. They are rapidly activated by various cytokines, hormones, and growth factors. Upon ligand binding and cytokine receptor dimerization, Stat proteins are phosphorylated on tyrosine residues by Jak kinases. Activated Stat proteins form homo- or heterodimers, translocate to the nucleus, and induce transcription from responsive genes. Stat5 and Stat6 are transcription factors active in mammary epithelial cells and immune cells. Prolactin activates Stat5, and interleukin-4 (IL-4) activates Stat6. Both cytokines are able to stimulate cell proliferation, differentiation, and survival. We investigated the transactivation potential of Stat6 and found that it is not restricted to lymphocytes. IL-4-dependent activation of Stat6 was also observed in HC11 mammary epithelial cells. In these cells, Stat6 activation led to the induction of the beta-casein gene promoter. The induction of this promoter was confirmed in COS7 cells. The glucocorticoid receptor was able to further enhance IL-4-induced gene transcription through the action of Stat6. Deletion analysis of the carboxyl-terminal region of Stat6 and recombination of this region with a heterologous DNA binding domain allowed the delimitation and characterization of the transactivation domain of Stat6. The potencies of the transactivation domains of Stat5, Stat6, and viral protein VP16 were compared. Stat6 had a transactivation domain which was about 10-fold stronger than that of Stat5. In pre-B cells (Ba/F3), the transactivation domain of Stat6 was IL-4 regulated, independently from its DNA binding function.\n"
],
"offsets": [
[
0,
1871
]
]
}
] | [
{
"id": "PMID-9199300_T1",
"type": "Protein",
"text": [
"Stat5"
],
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[
45,
50
]
],
"normalized": []
},
{
"id": "PMID-9199300_T2",
"type": "Protein",
"text": [
"Stat6"
],
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[
55,
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]
],
"normalized": []
},
{
"id": "PMID-9199300_T3",
"type": "Protein",
"text": [
"Stat5"
],
"offsets": [
[
630,
635
]
],
"normalized": []
},
{
"id": "PMID-9199300_T4",
"type": "Protein",
"text": [
"Stat6"
],
"offsets": [
[
640,
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]
],
"normalized": []
},
{
"id": "PMID-9199300_T5",
"type": "Protein",
"text": [
"Prolactin"
],
"offsets": [
[
725,
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]
],
"normalized": []
},
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"id": "PMID-9199300_T6",
"type": "Protein",
"text": [
"Stat5"
],
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[
745,
750
]
],
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},
{
"id": "PMID-9199300_T7",
"type": "Protein",
"text": [
"interleukin-4"
],
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[
756,
769
]
],
"normalized": []
},
{
"id": "PMID-9199300_T8",
"type": "Protein",
"text": [
"IL-4"
],
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[
771,
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]
],
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},
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"id": "PMID-9199300_T9",
"type": "Protein",
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"Stat6"
],
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787,
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]
],
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},
{
"id": "PMID-9199300_T10",
"type": "Protein",
"text": [
"Stat6"
],
"offsets": [
[
931,
936
]
],
"normalized": []
},
{
"id": "PMID-9199300_T11",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
989,
993
]
],
"normalized": []
},
{
"id": "PMID-9199300_T12",
"type": "Protein",
"text": [
"Stat6"
],
"offsets": [
[
1018,
1023
]
],
"normalized": []
},
{
"id": "PMID-9199300_T13",
"type": "Protein",
"text": [
"Stat6"
],
"offsets": [
[
1092,
1097
]
],
"normalized": []
},
{
"id": "PMID-9199300_T14",
"type": "Protein",
"text": [
"glucocorticoid receptor"
],
"offsets": [
[
1228,
1251
]
],
"normalized": []
},
{
"id": "PMID-9199300_T15",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
1280,
1284
]
],
"normalized": []
},
{
"id": "PMID-9199300_T16",
"type": "Protein",
"text": [
"Stat6"
],
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[
1334,
1339
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],
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},
{
"id": "PMID-9199300_T17",
"type": "Protein",
"text": [
"Stat6"
],
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[
1394,
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],
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},
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"id": "PMID-9199300_T18",
"type": "Protein",
"text": [
"Stat6"
],
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1551,
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],
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},
{
"id": "PMID-9199300_T19",
"type": "Protein",
"text": [
"Stat5"
],
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[
1606,
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]
],
"normalized": []
},
{
"id": "PMID-9199300_T20",
"type": "Protein",
"text": [
"Stat6"
],
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[
1613,
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]
],
"normalized": []
},
{
"id": "PMID-9199300_T21",
"type": "Protein",
"text": [
"VP16"
],
"offsets": [
[
1638,
1642
]
],
"normalized": []
},
{
"id": "PMID-9199300_T22",
"type": "Protein",
"text": [
"Stat6"
],
"offsets": [
[
1658,
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]
],
"normalized": []
},
{
"id": "PMID-9199300_T23",
"type": "Protein",
"text": [
"Stat5"
],
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[
1739,
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],
"normalized": []
},
{
"id": "PMID-9199300_T24",
"type": "Protein",
"text": [
"Stat6"
],
"offsets": [
[
1800,
1805
]
],
"normalized": []
},
{
"id": "PMID-9199300_T25",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
1810,
1814
]
],
"normalized": []
},
{
"id": "PMID-9199300_T26",
"type": "Entity",
"text": [
"transactivation domains"
],
"offsets": [
[
18,
41
]
],
"normalized": []
},
{
"id": "PMID-9199300_T27",
"type": "Entity",
"text": [
"ligand"
],
"offsets": [
[
381,
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]
],
"normalized": []
},
{
"id": "PMID-9199300_T28",
"type": "Entity",
"text": [
"tyrosine residues"
],
"offsets": [
[
468,
485
]
],
"normalized": []
},
{
"id": "PMID-9199300_T29",
"type": "Entity",
"text": [
"responsive genes"
],
"offsets": [
[
612,
628
]
],
"normalized": []
},
{
"id": "PMID-9199300_T30",
"type": "Entity",
"text": [
"beta-casein gene promoter"
],
"offsets": [
[
1137,
1162
]
],
"normalized": []
},
{
"id": "PMID-9199300_T31",
"type": "Entity",
"text": [
"carboxyl-terminal region"
],
"offsets": [
[
1366,
1390
]
],
"normalized": []
},
{
"id": "PMID-9199300_T32",
"type": "Entity",
"text": [
"heterologous DNA binding domain"
],
"offsets": [
[
1440,
1471
]
],
"normalized": []
},
{
"id": "PMID-9199300_T33",
"type": "Entity",
"text": [
"transactivation domains"
],
"offsets": [
[
1579,
1602
]
],
"normalized": []
},
{
"id": "PMID-9199300_T34",
"type": "Entity",
"text": [
"transactivation domain"
],
"offsets": [
[
1774,
1796
]
],
"normalized": []
}
] | [] | [
{
"id": "PMID-9199300_1",
"entity_ids": [
"PMID-9199300_T7",
"PMID-9199300_T8"
]
}
] | [
{
"id": "PMID-9199300_R1",
"type": "Protein-Component",
"arg1_id": "PMID-9199300_T1",
"arg2_id": "PMID-9199300_T26",
"normalized": []
},
{
"id": "PMID-9199300_R2",
"type": "Protein-Component",
"arg1_id": "PMID-9199300_T2",
"arg2_id": "PMID-9199300_T26",
"normalized": []
},
{
"id": "PMID-9199300_R3",
"type": "Protein-Component",
"arg1_id": "PMID-9199300_T17",
"arg2_id": "PMID-9199300_T32",
"normalized": []
},
{
"id": "PMID-9199300_R4",
"type": "Protein-Component",
"arg1_id": "PMID-9199300_T17",
"arg2_id": "PMID-9199300_T31",
"normalized": []
},
{
"id": "PMID-9199300_R5",
"type": "Protein-Component",
"arg1_id": "PMID-9199300_T21",
"arg2_id": "PMID-9199300_T33",
"normalized": []
},
{
"id": "PMID-9199300_R6",
"type": "Protein-Component",
"arg1_id": "PMID-9199300_T20",
"arg2_id": "PMID-9199300_T33",
"normalized": []
},
{
"id": "PMID-9199300_R7",
"type": "Protein-Component",
"arg1_id": "PMID-9199300_T19",
"arg2_id": "PMID-9199300_T33",
"normalized": []
},
{
"id": "PMID-9199300_R8",
"type": "Protein-Component",
"arg1_id": "PMID-9199300_T24",
"arg2_id": "PMID-9199300_T34",
"normalized": []
}
] |
130 | PMID-8666795 | [
{
"id": "PMID-8666795__text",
"type": "abstract",
"text": [
"Induction of CIITA and modification of in vivo HLA-DR promoter occupancy in normal thymic epithelial cells treated with IFN-gamma: similarities and distinctions with respect to HLA-DR-constitutive B cells. \nIn this study, the IFN-gamma induction of MHC class II gene expression in primary cultures of thymic epithelial cells (TEC) was analyzed. This cellular system offers the advantage that MHC class II induction is studied in a \"physiologic\" cell lineage that, as a result of this expression within the thymus, is thought to participate to the selection and maturation of the T cells. It was found that the MHC class II gene expression was associated with the de novo transcription of the gene encoding the CIITA trans-activator, a crucial MHC class II gene regulatory factor. Furthermore, the anatomy of interaction between the MHC class II DRA promoter and corresponding binding factors was analyzed by in vivo DNAse I footprint. It was found that treatment with IFN-gamma induces changes in the occupancy of the DRA gene regulatory sequences by nuclear factors. The resulting occupancy displays strong similarities with the one observed in the MHC class II-constitutive B cells, represented by both the Burkitt lymphoma line Raji and normal tonsil- derived B cells. However, some peculiar differences were observed between the TEC, either IFN-gamma-induced or not, and the constitutive B cells. These results suggest that both common mechanisms, such as the one mediated by the CIITA trans-activator, and distinct tissue-specific constraints contribute to the transcriptional control of constitutive and IFN-gamma-induced MHC class II gene expression.\n"
],
"offsets": [
[
0,
1658
]
]
}
] | [
{
"id": "PMID-8666795_T1",
"type": "Protein",
"text": [
"CIITA"
],
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[
13,
18
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{
"id": "PMID-8666795_T2",
"type": "Protein",
"text": [
"IFN-gamma"
],
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120,
129
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{
"id": "PMID-8666795_T3",
"type": "Protein",
"text": [
"IFN-gamma"
],
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226,
235
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"normalized": []
},
{
"id": "PMID-8666795_T4",
"type": "Protein",
"text": [
"CIITA"
],
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"id": "PMID-8666795_T5",
"type": "Protein",
"text": [
"IFN-gamma"
],
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"id": "PMID-8666795_T6",
"type": "Protein",
"text": [
"IFN-gamma"
],
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1345,
1354
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"id": "PMID-8666795_T7",
"type": "Protein",
"text": [
"CIITA"
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"id": "PMID-8666795_T8",
"type": "Protein",
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"IFN-gamma"
],
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1610,
1619
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"id": "PMID-8666795_T9",
"type": "Entity",
"text": [
"HLA-DR promoter"
],
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47,
62
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},
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"id": "PMID-8666795_T10",
"type": "Entity",
"text": [
"MHC class II gene"
],
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249,
266
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"id": "PMID-8666795_T11",
"type": "Entity",
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"MHC class II gene"
],
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610,
627
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"id": "PMID-8666795_T12",
"type": "Entity",
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"MHC class II gene"
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"id": "PMID-8666795_T13",
"type": "Entity",
"text": [
"MHC class II DRA promoter"
],
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832,
857
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],
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},
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"id": "PMID-8666795_T14",
"type": "Entity",
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"DRA gene regulatory sequences"
],
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1018,
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},
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"id": "PMID-8666795_T15",
"type": "Entity",
"text": [
"MHC class II gene"
],
"offsets": [
[
1628,
1645
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],
"normalized": []
}
] | [] | [] | [] |
131 | PMID-2105887 | [
{
"id": "PMID-2105887__text",
"type": "abstract",
"text": [
"A factor known to bind to endogenous Ig heavy chain enhancer only in lymphocytes is a ubiquitously active transcription factor. \nThe transcriptional enhancer located in the first intron of the immunoglobulin heavy chain constant region is a major determinant of B-cell-specific expression of immunoglobulin genes. Like other enhancers, the Ig heavy chain enhancer contains several short sequence motifs that bind specific transcription factors. Each binding site contributes to the overall activity of the enhancer, however no single element seems absolutely required for activity. For a better understanding of the Ig heavy chain enhancer components, we have cloned and analyzed individual sequence elements. We find that the factor that binds to the E3 enhancer motif, CATGTGGC, is a ubiquitous transcription factor. It is present in an active form in both B cells and non-B cells, where it can mediate transcriptional activation in vitro and in vivo. However, despite its ability to activate transcription of a transfected reporter gene, the factor is apparently unable to bind to the endogenous Ig heavy chain enhancer in non-lymphoid cells: In previous experiments by others, the characteristic in vivo footprint of this factor, designated NF-muE3, was detected in B cells but not in non-B cells. From this and other findings the picture emerges that there are at least three categories of factors which mediate cell-type-specific transcription in B lymphocytes: (a) cell-specific factors such as Oct-2A and Oct-2B that are not expressed in most other cell types: (b) ubiquitous factors such as NF-kappa B that are constitutively active in B cells but are sequestered in an inactive form in other cells; (c) ubiquitously active factors, exemplified by the one binding to the E3 sequence motif. This factor is present in an active form in a variety of cell types but is apparently unable to bind to the endogenous Ig heavy chain enhancer in non-B cells, perhaps due to a non-permissive chromatin structure of the Ig heavy chain locus.\n"
],
"offsets": [
[
0,
2039
]
]
}
] | [
{
"id": "PMID-2105887_T1",
"type": "Protein",
"text": [
"NF-muE3"
],
"offsets": [
[
1245,
1252
]
],
"normalized": []
},
{
"id": "PMID-2105887_T2",
"type": "Protein",
"text": [
"Oct-2A"
],
"offsets": [
[
1502,
1508
]
],
"normalized": []
},
{
"id": "PMID-2105887_T3",
"type": "Protein",
"text": [
"Oct-2B"
],
"offsets": [
[
1513,
1519
]
],
"normalized": []
},
{
"id": "PMID-2105887_T4",
"type": "Entity",
"text": [
"endogenous Ig heavy chain enhancer"
],
"offsets": [
[
26,
60
]
],
"normalized": []
},
{
"id": "PMID-2105887_T5",
"type": "Entity",
"text": [
"transcriptional enhancer"
],
"offsets": [
[
133,
157
]
],
"normalized": []
},
{
"id": "PMID-2105887_T6",
"type": "Entity",
"text": [
"immunoglobulin heavy chain constant region"
],
"offsets": [
[
193,
235
]
],
"normalized": []
},
{
"id": "PMID-2105887_T7",
"type": "Entity",
"text": [
"immunoglobulin genes"
],
"offsets": [
[
292,
312
]
],
"normalized": []
},
{
"id": "PMID-2105887_T8",
"type": "Entity",
"text": [
"enhancers"
],
"offsets": [
[
325,
334
]
],
"normalized": []
},
{
"id": "PMID-2105887_T9",
"type": "Entity",
"text": [
"Ig heavy chain enhancer"
],
"offsets": [
[
340,
363
]
],
"normalized": []
},
{
"id": "PMID-2105887_T10",
"type": "Entity",
"text": [
"sequence motifs"
],
"offsets": [
[
387,
402
]
],
"normalized": []
},
{
"id": "PMID-2105887_T11",
"type": "Entity",
"text": [
"binding site"
],
"offsets": [
[
450,
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]
],
"normalized": []
},
{
"id": "PMID-2105887_T12",
"type": "Entity",
"text": [
"enhancer"
],
"offsets": [
[
506,
514
]
],
"normalized": []
},
{
"id": "PMID-2105887_T13",
"type": "Entity",
"text": [
"single element"
],
"offsets": [
[
527,
541
]
],
"normalized": []
},
{
"id": "PMID-2105887_T14",
"type": "Entity",
"text": [
"Ig heavy chain enhancer components"
],
"offsets": [
[
616,
650
]
],
"normalized": []
},
{
"id": "PMID-2105887_T15",
"type": "Entity",
"text": [
"sequence elements"
],
"offsets": [
[
691,
708
]
],
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},
{
"id": "PMID-2105887_T16",
"type": "Entity",
"text": [
"E3 enhancer motif"
],
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[
752,
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],
"normalized": []
},
{
"id": "PMID-2105887_T17",
"type": "Entity",
"text": [
"CATGTGGC"
],
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[
771,
779
]
],
"normalized": []
},
{
"id": "PMID-2105887_T18",
"type": "Entity",
"text": [
"transfected reporter gene"
],
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[
1014,
1039
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],
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},
{
"id": "PMID-2105887_T19",
"type": "Entity",
"text": [
"Ig heavy chain enhancer"
],
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[
1099,
1122
]
],
"normalized": []
},
{
"id": "PMID-2105887_T20",
"type": "Entity",
"text": [
"NF-kappa B"
],
"offsets": [
[
1600,
1610
]
],
"normalized": []
},
{
"id": "PMID-2105887_T21",
"type": "Entity",
"text": [
"E3 sequence motif"
],
"offsets": [
[
1780,
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]
],
"normalized": []
},
{
"id": "PMID-2105887_T22",
"type": "Entity",
"text": [
"Ig heavy chain enhancer"
],
"offsets": [
[
1918,
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]
],
"normalized": []
},
{
"id": "PMID-2105887_T23",
"type": "Entity",
"text": [
"chromatin"
],
"offsets": [
[
1990,
1999
]
],
"normalized": []
},
{
"id": "PMID-2105887_T24",
"type": "Entity",
"text": [
"Ig heavy chain locus"
],
"offsets": [
[
2017,
2037
]
],
"normalized": []
}
] | [] | [] | [] |
132 | PMID-8480425 | [
{
"id": "PMID-8480425__text",
"type": "abstract",
"text": [
"HIV-1 Nef protein inhibits the recruitment of AP-1 DNA-binding activity in human T-cells. \nThe human immunodeficiency virus type 1 long terminal repeat, HIV-1-LTR, contains binding sites for several cellular transcription factors which contribute to HIV-1 gene expression. Our previous studies on the function of the HIV-1-encoded Nef protein suggested that Nef may be an inhibitor HIV-1 transcription. To determine whether Nef affects the binding of cellular factors implicated in HIV-1 regulation, 32P-labeled oligonucleotides corresponding to the binding sites were incubated with nuclear extracts prepared from Nef-expressing T-cell lines that were not stimulated or were stimulated with T-cell mitogens. We found that Nef inhibited the recruitment of AP-1 DNA-binding activity in mitogen-stimulated human T-cells. Additionally, Nef expressing cells were transiently transfected with a plasmid in which HIV-1 AP-1 DNA recognition sequences were cloned downstream of the chloramphenicol acetyltransferase (CAT) gene. Mitogen-mediated transcriptional activation of the CAT gene in this construct was inhibited in Nef-expressing cells but not in control cells. These studies suggest that, by inhibiting AP-1 activation, Nef may play a role in regulating HIV-1 gene expression in infected T-cells.\n"
],
"offsets": [
[
0,
1298
]
]
}
] | [
{
"id": "PMID-8480425_T1",
"type": "Protein",
"text": [
"Nef"
],
"offsets": [
[
6,
9
]
],
"normalized": []
},
{
"id": "PMID-8480425_T2",
"type": "Protein",
"text": [
"Nef"
],
"offsets": [
[
331,
334
]
],
"normalized": []
},
{
"id": "PMID-8480425_T3",
"type": "Protein",
"text": [
"Nef"
],
"offsets": [
[
358,
361
]
],
"normalized": []
},
{
"id": "PMID-8480425_T4",
"type": "Protein",
"text": [
"Nef"
],
"offsets": [
[
424,
427
]
],
"normalized": []
},
{
"id": "PMID-8480425_T5",
"type": "Protein",
"text": [
"Nef"
],
"offsets": [
[
615,
618
]
],
"normalized": []
},
{
"id": "PMID-8480425_T6",
"type": "Protein",
"text": [
"Nef"
],
"offsets": [
[
723,
726
]
],
"normalized": []
},
{
"id": "PMID-8480425_T7",
"type": "Protein",
"text": [
"Nef"
],
"offsets": [
[
833,
836
]
],
"normalized": []
},
{
"id": "PMID-8480425_T8",
"type": "Protein",
"text": [
"chloramphenicol acetyltransferase"
],
"offsets": [
[
974,
1007
]
],
"normalized": []
},
{
"id": "PMID-8480425_T9",
"type": "Protein",
"text": [
"CAT"
],
"offsets": [
[
1009,
1012
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],
"normalized": []
},
{
"id": "PMID-8480425_T10",
"type": "Protein",
"text": [
"CAT"
],
"offsets": [
[
1071,
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],
"normalized": []
},
{
"id": "PMID-8480425_T11",
"type": "Protein",
"text": [
"Nef"
],
"offsets": [
[
1115,
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],
"normalized": []
},
{
"id": "PMID-8480425_T12",
"type": "Protein",
"text": [
"Nef"
],
"offsets": [
[
1221,
1224
]
],
"normalized": []
},
{
"id": "PMID-8480425_T13",
"type": "Entity",
"text": [
"AP-1"
],
"offsets": [
[
46,
50
]
],
"normalized": []
},
{
"id": "PMID-8480425_T14",
"type": "Entity",
"text": [
"DNA"
],
"offsets": [
[
51,
54
]
],
"normalized": []
},
{
"id": "PMID-8480425_T15",
"type": "Entity",
"text": [
"human immunodeficiency virus type 1 long terminal repeat"
],
"offsets": [
[
95,
151
]
],
"normalized": []
},
{
"id": "PMID-8480425_T16",
"type": "Entity",
"text": [
"HIV-1-LTR"
],
"offsets": [
[
153,
162
]
],
"normalized": []
},
{
"id": "PMID-8480425_T17",
"type": "Entity",
"text": [
"binding sites for several cellular transcription factors"
],
"offsets": [
[
173,
229
]
],
"normalized": []
},
{
"id": "PMID-8480425_T18",
"type": "Entity",
"text": [
"32P-labeled oligonucleotides"
],
"offsets": [
[
500,
528
]
],
"normalized": []
},
{
"id": "PMID-8480425_T19",
"type": "Entity",
"text": [
"AP-1"
],
"offsets": [
[
756,
760
]
],
"normalized": []
},
{
"id": "PMID-8480425_T20",
"type": "Entity",
"text": [
"DNA"
],
"offsets": [
[
761,
764
]
],
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},
{
"id": "PMID-8480425_T21",
"type": "Entity",
"text": [
"HIV-1 AP-1 DNA recognition sequences"
],
"offsets": [
[
907,
943
]
],
"normalized": []
},
{
"id": "PMID-8480425_T22",
"type": "Entity",
"text": [
"AP-1"
],
"offsets": [
[
913,
917
]
],
"normalized": []
},
{
"id": "PMID-8480425_T23",
"type": "Entity",
"text": [
"AP-1"
],
"offsets": [
[
1204,
1208
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],
"normalized": []
},
{
"id": "PMID-8480425_T24",
"type": "Entity",
"text": [
"HIV-1 gene"
],
"offsets": [
[
1255,
1265
]
],
"normalized": []
}
] | [] | [
{
"id": "PMID-8480425_1",
"entity_ids": [
"PMID-8480425_T8",
"PMID-8480425_T9"
]
}
] | [] |
133 | PMID-8608243 | [
{
"id": "PMID-8608243__text",
"type": "abstract",
"text": [
"AM580, a stable benzoic derivative of retinoic acid, has powerful and selective cyto-differentiating effects on acute promyelocytic leukemia cells. \nAll-trans retinoic acid (ATRA) is successfully used in the cyto-differentiating treatment of acute promyelocytic leukemia (APL). Paradoxically, APL cells express PML-RAR, an aberrant form of the retinoic acid receptor type alpha (RAR alpha) derived from the leukemia-specific t(15;17) chromosomal translocation. We show here that AM580, a stable retinobenzoic derivative originally synthesized as a RAR alpha agonist, is a powerful inducer of granulocytic maturation in NB4, an APL-derived cell line, and in freshly isolated APL blasts. After treatment of APL cells with AM580 either alone or in combination with granulocyte colony-stimulating factor (G-CSF), the compound induces granulocytic maturation, as assessed by determination of the levels of leukocyte alkaline phosphatase, CD11b, CD33, and G-CSF receptor mRNA, at concentrations that are 10- to 100-fold lower than those of ATRA necessary to produce similar effects. By contrast, AM580 is not effective as ATRA in modulating the expression of these differentiation markers in the HL-60 cell line and in freshly isolated granulocytes obtained from the peripheral blood of chronic myelogenous leukemia patients during the stable phase of the disease. In NB4 cells, two other synthetic nonselective RAR ligands are capable of inducing LAP as much as AM580, whereas RAR beta- or RAR gamma-specific ligands are totally ineffective. These results show that AM580 is more powerful than ATRA in modulating the expression of differentiation antigens only in cells in which PML-RAR is present. Binding experiments, using COS-7 cells transiently transfected with PML-RAR and the normal RAR alpha, show that AM580 has a lower affinity than ATRA for both receptors. However, in the presence of PML-RAR, the synthetic retinoid is a much better transactivator of retinoic acid-responsive element-containing promoters than the natural retinoid, whereas, in the presence of RAR alpha, AM580 and ATRA have similar activity. This may explain the strong cyto-differentiating potential of AM580 in PML-RAR-containing leukemic cells.\n"
],
"offsets": [
[
0,
2222
]
]
}
] | [
{
"id": "PMID-8608243_T1",
"type": "Protein",
"text": [
"PML-RAR"
],
"offsets": [
[
311,
318
]
],
"normalized": []
},
{
"id": "PMID-8608243_T2",
"type": "Protein",
"text": [
"retinoic acid receptor type alpha"
],
"offsets": [
[
344,
377
]
],
"normalized": []
},
{
"id": "PMID-8608243_T3",
"type": "Protein",
"text": [
"RAR alpha"
],
"offsets": [
[
379,
388
]
],
"normalized": []
},
{
"id": "PMID-8608243_T4",
"type": "Protein",
"text": [
"RAR alpha"
],
"offsets": [
[
548,
557
]
],
"normalized": []
},
{
"id": "PMID-8608243_T5",
"type": "Protein",
"text": [
"granulocyte colony-stimulating factor"
],
"offsets": [
[
762,
799
]
],
"normalized": []
},
{
"id": "PMID-8608243_T6",
"type": "Protein",
"text": [
"G-CSF"
],
"offsets": [
[
801,
806
]
],
"normalized": []
},
{
"id": "PMID-8608243_T7",
"type": "Protein",
"text": [
"leukocyte alkaline phosphatase"
],
"offsets": [
[
901,
931
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],
"normalized": []
},
{
"id": "PMID-8608243_T8",
"type": "Protein",
"text": [
"CD11b"
],
"offsets": [
[
933,
938
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],
"normalized": []
},
{
"id": "PMID-8608243_T9",
"type": "Protein",
"text": [
"CD33"
],
"offsets": [
[
940,
944
]
],
"normalized": []
},
{
"id": "PMID-8608243_T10",
"type": "Protein",
"text": [
"G-CSF receptor"
],
"offsets": [
[
950,
964
]
],
"normalized": []
},
{
"id": "PMID-8608243_T11",
"type": "Protein",
"text": [
"LAP"
],
"offsets": [
[
1442,
1445
]
],
"normalized": []
},
{
"id": "PMID-8608243_T12",
"type": "Protein",
"text": [
"RAR beta"
],
"offsets": [
[
1472,
1480
]
],
"normalized": []
},
{
"id": "PMID-8608243_T13",
"type": "Protein",
"text": [
"RAR gamma"
],
"offsets": [
[
1485,
1494
]
],
"normalized": []
},
{
"id": "PMID-8608243_T14",
"type": "Protein",
"text": [
"PML-RAR"
],
"offsets": [
[
1674,
1681
]
],
"normalized": []
},
{
"id": "PMID-8608243_T15",
"type": "Protein",
"text": [
"PML-RAR"
],
"offsets": [
[
1762,
1769
]
],
"normalized": []
},
{
"id": "PMID-8608243_T16",
"type": "Protein",
"text": [
"RAR alpha"
],
"offsets": [
[
1785,
1794
]
],
"normalized": []
},
{
"id": "PMID-8608243_T17",
"type": "Protein",
"text": [
"PML-RAR"
],
"offsets": [
[
1891,
1898
]
],
"normalized": []
},
{
"id": "PMID-8608243_T18",
"type": "Protein",
"text": [
"RAR alpha"
],
"offsets": [
[
2067,
2076
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],
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},
{
"id": "PMID-8608243_T19",
"type": "Protein",
"text": [
"PML-RAR"
],
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2194
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],
"normalized": []
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"id": "PMID-8608243_T20",
"type": "Entity",
"text": [
"retinoic acid-responsive element-containing promoters"
],
"offsets": [
[
1958,
2011
]
],
"normalized": []
}
] | [] | [
{
"id": "PMID-8608243_1",
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"PMID-8608243_T2",
"PMID-8608243_T3"
]
},
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"id": "PMID-8608243_2",
"entity_ids": [
"PMID-8608243_T5",
"PMID-8608243_T6"
]
}
] | [] |
134 | PMID-9144472 | [
{
"id": "PMID-9144472__text",
"type": "abstract",
"text": [
"Regulation of CD95 (Fas) ligand expression by TCR-mediated signaling events. \nStimulation of mature peripheral T cells by TCR engagement results in activation of signals that drive induction of cytokine gene expression and clonal expansion. However, under some conditions, engagement of the TCR leads instead to apoptosis. Recent studies demonstrate that TCR-stimulated apoptosis requires expression of CD95 ligand on activated T cells followed by an interaction between CD95 ligand and the CD95 receptor also expressed on this population. The experiments reported in this study were designed to address the signaling events triggered by TCR engagement that are important for regulating CD95 ligand gene expression. To approach this, we generated a luciferase reporter construct containing elements of the CD95 ligand promoter. Using a previously described mutant of the Jurkat T cell line, we show that proximal signaling events dependent on the presence of the CD45 tyrosine phosphatase are required for TCR-stimulated CD95 ligand expression. Transient transfection studies demonstrate further that TCR-stimulated activation of the Ras signaling pathway is required for optimal activation of CD95 ligand. Next, in an effort to determine critical transcription factors that regulate CD95 ligand expression, we demonstrate a cyclosporin A-sensitive nuclear factor-AT response element in the promoter region of this gene that is critical for optimal CD95 ligand reporter activity in stimulated T cells. Together, these studies begin a dissection of the biochemical events that lead to expression of CD95 ligand, a required step for TCR-induced apoptosis.\n"
],
"offsets": [
[
0,
1654
]
]
}
] | [
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"id": "PMID-9144472_T1",
"type": "Protein",
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"CD95 (Fas) ligand"
],
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31
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"id": "PMID-9144472_T2",
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"CD95 ligand"
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"id": "PMID-9144472_T3",
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"CD95 ligand"
],
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482
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"id": "PMID-9144472_T4",
"type": "Protein",
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"CD95"
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"id": "PMID-9144472_T5",
"type": "Protein",
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"CD95 ligand"
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"id": "PMID-9144472_T6",
"type": "Protein",
"text": [
"luciferase"
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759
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"id": "PMID-9144472_T7",
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"CD95 ligand"
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"id": "PMID-9144472_T8",
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"CD45 tyrosine phosphatase"
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"CD95 ligand"
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"CD95 ligand"
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"type": "Protein",
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"CD95 ligand"
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},
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"id": "PMID-9144472_T12",
"type": "Protein",
"text": [
"cyclosporin A"
],
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1325,
1338
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},
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"id": "PMID-9144472_T13",
"type": "Protein",
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"CD95 ligand"
],
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},
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"id": "PMID-9144472_T14",
"type": "Protein",
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"CD95 ligand"
],
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1598,
1609
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},
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"id": "PMID-9144472_T15",
"type": "Entity",
"text": [
"cytokine gene"
],
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194,
207
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],
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},
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"id": "PMID-9144472_T16",
"type": "Entity",
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"promoter"
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826
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},
{
"id": "PMID-9144472_T17",
"type": "Entity",
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"-sensitive nuclear factor-AT response element"
],
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1338,
1383
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"id": "PMID-9144472_T18",
"type": "Entity",
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"promoter region"
],
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1391,
1406
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"id": "PMID-9144472_T19",
"type": "Entity",
"text": [
"reporter"
],
"offsets": [
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1461,
1469
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],
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}
] | [] | [] | [
{
"id": "PMID-9144472_R1",
"type": "Protein-Component",
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},
{
"id": "PMID-9144472_R2",
"type": "Protein-Component",
"arg1_id": "PMID-9144472_T11",
"arg2_id": "PMID-9144472_T17",
"normalized": []
}
] |
135 | PMID-9326236 | [
{
"id": "PMID-9326236__text",
"type": "abstract",
"text": [
"Interleukin-7 upregulates the interleukin-2-gene expression in activated human T lymphocytes at the transcriptional level by enhancing the DNA binding activities of both nuclear factor of activated T cells and activator protein-1. \nIn the present report, we studied the role of the stromal-derived cytokine interleukin-7 (IL-7) in the IL-2-gene regulation in activated T lymphocytes. Production of IL-2 requires the formation of transcription factors involved in the IL-2-gene regulation. T-cell receptor (TCR)/CD3 engagement results in the activation of nuclear factor of activated T cells (NFAT), activator protein-1 (AP-1), and nuclear factor kappaB (NFkappaB), whereas the CD28 responsive complex (CD28RC) is activated in response to the CD28 signal. Costimulation of phytohemagglutinin/anti-CD28 activated T lymphocytes with IL-7 induces a fivefold enhanced IL-2-mRNA accumulation and a 2.5-fold enhanced protein secretion. The IL-2-gene transcription rate is increased 3.4-fold, indicating that the effect of IL-7 is in part mediated at the transcriptional level. The molecular mechanisms underlying the IL-7 effect involve the upregulation of the DNA binding activity of NFAT (60%) and AP-1 (120%), without affecting the activities of NFkappaB and CD28RC, which was confirmed by transfection assays. We also show that the IL-7-induced enhancement of the AP-1-DNA binding activity is not cyclosporin A-sensitive. Since AP-1 is part of the NFAT complex, we conclude that the IL-7-signaling pathway is involved in the activation of the fos and jun proteins of which AP-1 consists.\n"
],
"offsets": [
[
0,
1585
]
]
}
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"id": "PMID-9326236_T1",
"type": "Protein",
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"Interleukin-7"
],
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0,
13
]
],
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},
{
"id": "PMID-9326236_T2",
"type": "Protein",
"text": [
"interleukin-2"
],
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30,
43
]
],
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},
{
"id": "PMID-9326236_T3",
"type": "Protein",
"text": [
"interleukin-7"
],
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307,
320
]
],
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},
{
"id": "PMID-9326236_T4",
"type": "Protein",
"text": [
"IL-7"
],
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322,
326
]
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},
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"id": "PMID-9326236_T5",
"type": "Protein",
"text": [
"IL-2"
],
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335,
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]
],
"normalized": []
},
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"id": "PMID-9326236_T6",
"type": "Protein",
"text": [
"IL-2"
],
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398,
402
]
],
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},
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"id": "PMID-9326236_T7",
"type": "Protein",
"text": [
"IL-2"
],
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467,
471
]
],
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},
{
"id": "PMID-9326236_T8",
"type": "Protein",
"text": [
"CD28"
],
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742,
746
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],
"normalized": []
},
{
"id": "PMID-9326236_T9",
"type": "Protein",
"text": [
"phytohemagglutinin"
],
"offsets": [
[
772,
790
]
],
"normalized": []
},
{
"id": "PMID-9326236_T10",
"type": "Protein",
"text": [
"CD28"
],
"offsets": [
[
796,
800
]
],
"normalized": []
},
{
"id": "PMID-9326236_T11",
"type": "Protein",
"text": [
"IL-7"
],
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[
830,
834
]
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"normalized": []
},
{
"id": "PMID-9326236_T12",
"type": "Protein",
"text": [
"IL-2"
],
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[
863,
867
]
],
"normalized": []
},
{
"id": "PMID-9326236_T13",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
933,
937
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],
"normalized": []
},
{
"id": "PMID-9326236_T14",
"type": "Protein",
"text": [
"IL-7"
],
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[
1015,
1019
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},
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"id": "PMID-9326236_T15",
"type": "Protein",
"text": [
"IL-7"
],
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1110,
1114
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"normalized": []
},
{
"id": "PMID-9326236_T16",
"type": "Protein",
"text": [
"IL-7"
],
"offsets": [
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1329,
1333
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],
"normalized": []
},
{
"id": "PMID-9326236_T17",
"type": "Protein",
"text": [
"IL-7"
],
"offsets": [
[
1480,
1484
]
],
"normalized": []
},
{
"id": "PMID-9326236_T18",
"type": "Protein",
"text": [
"fos"
],
"offsets": [
[
1540,
1543
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],
"normalized": []
},
{
"id": "PMID-9326236_T19",
"type": "Protein",
"text": [
"jun"
],
"offsets": [
[
1548,
1551
]
],
"normalized": []
},
{
"id": "PMID-9326236_T20",
"type": "Entity",
"text": [
"DNA"
],
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[
139,
142
]
],
"normalized": []
},
{
"id": "PMID-9326236_T21",
"type": "Entity",
"text": [
"activator protein-1"
],
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[
210,
229
]
],
"normalized": []
},
{
"id": "PMID-9326236_T22",
"type": "Entity",
"text": [
"T-cell receptor"
],
"offsets": [
[
489,
504
]
],
"normalized": []
},
{
"id": "PMID-9326236_T23",
"type": "Entity",
"text": [
"TCR"
],
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[
506,
509
]
],
"normalized": []
},
{
"id": "PMID-9326236_T24",
"type": "Entity",
"text": [
"CD3"
],
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[
511,
514
]
],
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},
{
"id": "PMID-9326236_T25",
"type": "Entity",
"text": [
"activator protein-1"
],
"offsets": [
[
599,
618
]
],
"normalized": []
},
{
"id": "PMID-9326236_T26",
"type": "Entity",
"text": [
"AP-1"
],
"offsets": [
[
620,
624
]
],
"normalized": []
},
{
"id": "PMID-9326236_T27",
"type": "Entity",
"text": [
"nuclear factor kappaB"
],
"offsets": [
[
631,
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]
],
"normalized": []
},
{
"id": "PMID-9326236_T28",
"type": "Entity",
"text": [
"NFkappaB"
],
"offsets": [
[
654,
662
]
],
"normalized": []
},
{
"id": "PMID-9326236_T29",
"type": "Entity",
"text": [
"CD28 responsive complex"
],
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677,
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]
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},
{
"id": "PMID-9326236_T30",
"type": "Entity",
"text": [
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],
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702,
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},
{
"id": "PMID-9326236_T31",
"type": "Entity",
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"DNA"
],
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1154,
1157
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},
{
"id": "PMID-9326236_T32",
"type": "Entity",
"text": [
"AP-1"
],
"offsets": [
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1193,
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"normalized": []
},
{
"id": "PMID-9326236_T33",
"type": "Entity",
"text": [
"NFkappaB"
],
"offsets": [
[
1242,
1250
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"normalized": []
},
{
"id": "PMID-9326236_T34",
"type": "Entity",
"text": [
"CD28RC"
],
"offsets": [
[
1255,
1261
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"normalized": []
},
{
"id": "PMID-9326236_T35",
"type": "Entity",
"text": [
"AP-1"
],
"offsets": [
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1361,
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"normalized": []
},
{
"id": "PMID-9326236_T36",
"type": "Entity",
"text": [
"DNA"
],
"offsets": [
[
1366,
1369
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],
"normalized": []
},
{
"id": "PMID-9326236_T37",
"type": "Entity",
"text": [
"cyclosporin A"
],
"offsets": [
[
1394,
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],
"normalized": []
},
{
"id": "PMID-9326236_T38",
"type": "Entity",
"text": [
"AP-1"
],
"offsets": [
[
1425,
1429
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],
"normalized": []
},
{
"id": "PMID-9326236_T39",
"type": "Entity",
"text": [
"NFAT complex"
],
"offsets": [
[
1445,
1457
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],
"normalized": []
},
{
"id": "PMID-9326236_T40",
"type": "Entity",
"text": [
"AP-1"
],
"offsets": [
[
1570,
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],
"normalized": []
}
] | [] | [
{
"id": "PMID-9326236_1",
"entity_ids": [
"PMID-9326236_T3",
"PMID-9326236_T4"
]
}
] | [
{
"id": "PMID-9326236_R1",
"type": "Subunit-Complex",
"arg1_id": "PMID-9326236_T19",
"arg2_id": "PMID-9326236_T40",
"normalized": []
},
{
"id": "PMID-9326236_R2",
"type": "Subunit-Complex",
"arg1_id": "PMID-9326236_T18",
"arg2_id": "PMID-9326236_T40",
"normalized": []
}
] |
136 | PMID-10064103 | [
{
"id": "PMID-10064103__text",
"type": "abstract",
"text": [
"Peripheral blood mononuclear cells isolated from patients with diabetic nephropathy show increased activation of the oxidative-stress sensitive transcription factor NF-kappaB. \nIncreased oxidative stress and subsequent activation of the transcription factor NF-kappaB has been linked to the development of late diabetic complications. To determine whether oxidative stress dependent NF-kappaB activation is evident in patients with diabetic nephropathy we used an Electrophoretic Mobility Shift Assay based semiquantitative detection system which enabled us to determine NF-kappaB activation in ex vivo isolated peripheral blood mononuclear cells. We examined 33 patients with diabetes mellitus (Type I and Type II). Patients with diabetic nephropathy showed higher NF-kappaB binding activity in Electrophoretic Mobility Shift Assays and stronger immunohistological staining for activated NF-kappaBp65 than patients without renal complications. NF-kappaB binding activity correlated with the degree of albuminuria (r = 0.316) and with thrombomodulin plasma concentrations (r = 0.33), indicative for albuminuria associated endothelial dysfunction. In a 3 day intervention study in which 600 mg of the antioxidant thioctic acid (alpha-lipoic acid) per day were given to nine patients with diabetic nephropathy oxidative stress in plasma samples was decreased by 48% and NF-kappaB binding activity in ex vivo isolated peripheral blood mononuclear cells by 38%. In conclusion, activation of the transcription factor NF-kappaB in ex vivo isolated peripheral blood mononuclear cells of patients with diabetes mellitus correlates with the degree of diabetic nephropathy. NF-kappaB activation is at least in part dependent on oxidative stress since thioctic acid (alpha-lipoic acid) reduced NF-kappaB binding activity.\n"
],
"offsets": [
[
0,
1811
]
]
}
] | [
{
"id": "PMID-10064103_T1",
"type": "Protein",
"text": [
"NF-kappaBp65"
],
"offsets": [
[
889,
901
]
],
"normalized": []
},
{
"id": "PMID-10064103_T2",
"type": "Protein",
"text": [
"thrombomodulin"
],
"offsets": [
[
1035,
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]
],
"normalized": []
},
{
"id": "PMID-10064103_T3",
"type": "Entity",
"text": [
"NF-kappaB"
],
"offsets": [
[
165,
174
]
],
"normalized": []
},
{
"id": "PMID-10064103_T4",
"type": "Entity",
"text": [
"transcription factor NF-kappaB"
],
"offsets": [
[
237,
267
]
],
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},
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"id": "PMID-10064103_T5",
"type": "Entity",
"text": [
"NF-kappaB"
],
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383,
392
]
],
"normalized": []
},
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"id": "PMID-10064103_T6",
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"text": [
"NF-kappaB"
],
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571,
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]
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"normalized": []
},
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"id": "PMID-10064103_T7",
"type": "Entity",
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],
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775
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},
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"id": "PMID-10064103_T8",
"type": "Entity",
"text": [
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],
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},
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"id": "PMID-10064103_T9",
"type": "Entity",
"text": [
"NF-kappaB"
],
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1368,
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},
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"id": "PMID-10064103_T10",
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],
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"id": "PMID-10064103_T11",
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},
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"id": "PMID-10064103_T12",
"type": "Entity",
"text": [
"NF-kappaB"
],
"offsets": [
[
1783,
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],
"normalized": []
}
] | [] | [] | [] |
137 | PMID-9130477 | [
{
"id": "PMID-9130477__text",
"type": "abstract",
"text": [
"Regulation of human epsilon germline transcription: role of B-cell-specific activator protein. \nGermline transcripts initiate from promoters upstream of the immunoglobulin switch region, and are necessary to target the appropriate switch region for recombination and switching. Different cytokines activate transcription at the appropriate germline promoter. Because binding sites for B-cell-specific activator protein (BSAP) are located upstream of several switch regions in the immunoglobulin heavy chain gene cluster, BSAP might play a role in the regulation of germline transcription and isotype switching. We investigated whether BSAP plays a role in the transcriptional regulation of the epsilon germline promoter in human B cells. Our results showed that BSAP plays a role in both IL-4-dependent induction and CD40-mediated upregulation of human epsilon germline transcription. BSAP is unique among the transcription factors that regulate epsilon germline expression, because it is B cell specific, and is at the merging point of two signalling pathways that are critical for IgE switching.\n"
],
"offsets": [
[
0,
1098
]
]
}
] | [
{
"id": "PMID-9130477_T1",
"type": "Protein",
"text": [
"B-cell-specific activator protein"
],
"offsets": [
[
60,
93
]
],
"normalized": []
},
{
"id": "PMID-9130477_T2",
"type": "Protein",
"text": [
"B-cell-specific activator protein"
],
"offsets": [
[
385,
418
]
],
"normalized": []
},
{
"id": "PMID-9130477_T3",
"type": "Protein",
"text": [
"BSAP"
],
"offsets": [
[
420,
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]
],
"normalized": []
},
{
"id": "PMID-9130477_T4",
"type": "Protein",
"text": [
"BSAP"
],
"offsets": [
[
521,
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]
],
"normalized": []
},
{
"id": "PMID-9130477_T5",
"type": "Protein",
"text": [
"BSAP"
],
"offsets": [
[
635,
639
]
],
"normalized": []
},
{
"id": "PMID-9130477_T6",
"type": "Protein",
"text": [
"BSAP"
],
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762,
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},
{
"id": "PMID-9130477_T7",
"type": "Protein",
"text": [
"IL-4"
],
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788,
792
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},
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"id": "PMID-9130477_T8",
"type": "Protein",
"text": [
"CD40"
],
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821
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},
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"id": "PMID-9130477_T9",
"type": "Protein",
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"BSAP"
],
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885,
889
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},
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"id": "PMID-9130477_T10",
"type": "Entity",
"text": [
"epsilon germline"
],
"offsets": [
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20,
36
]
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},
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"id": "PMID-9130477_T11",
"type": "Entity",
"text": [
"promoters"
],
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131,
140
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],
"normalized": []
},
{
"id": "PMID-9130477_T12",
"type": "Entity",
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"immunoglobulin switch region"
],
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157,
185
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},
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"id": "PMID-9130477_T13",
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],
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231,
244
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"id": "PMID-9130477_T14",
"type": "Entity",
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"germline promoter"
],
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340,
357
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},
{
"id": "PMID-9130477_T15",
"type": "Entity",
"text": [
"binding sites"
],
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367,
380
]
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},
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"id": "PMID-9130477_T16",
"type": "Entity",
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"immunoglobulin heavy chain gene cluster"
],
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480,
519
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"normalized": []
},
{
"id": "PMID-9130477_T17",
"type": "Entity",
"text": [
"germline"
],
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565,
573
]
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},
{
"id": "PMID-9130477_T18",
"type": "Entity",
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"epsilon germline promoter"
],
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694,
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},
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"id": "PMID-9130477_T19",
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"germline promoter"
],
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702,
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},
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"id": "PMID-9130477_T20",
"type": "Entity",
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"epsilon germline"
],
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853,
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"id": "PMID-9130477_T21",
"type": "Entity",
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"epsilon germline"
],
"offsets": [
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946,
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}
] | [] | [
{
"id": "PMID-9130477_1",
"entity_ids": [
"PMID-9130477_T2",
"PMID-9130477_T3"
]
}
] | [] |
138 | PMID-9119999 | [
{
"id": "PMID-9119999__text",
"type": "abstract",
"text": [
"HIV does not replicate in naive CD4 T cells stimulated with CD3/CD28. \nIn this report, we demonstrate that the T cell tropic strain of HIV, LAI, does not replicate in naive CD4 T cells stimulated by cross-linking CD3 and CD28. In contrast, LAI replicates well in memory CD4 T cells stimulated in the same way. Unlike this physiologically relevant stimulation, PHA stimulates productive LAI replication in both naive and memory T cells. These studies were conducted with highly purified (FACS-isolated) subsets of CD4 T cells identified by expression of both CD45RA and CD62L. Remixing of purified T cells showed that naive T cells do not suppress LAI replication in memory T cells and that memory T cells do not restore LAI expression in naive T cells. The suppression of productive LAI replication in naive T cells is not due to differential expression of viral coreceptors, nor is it due to inhibition of activation of the important HIV transcription factors, nuclear factor-kappaB and activator protein-1. The inherent resistance of naive T cells to productive HIV infection, coupled with their proliferative advantage as demonstrated here, provides a sound basis for proposed clinical therapies using ex vivo expansion and reinfusion of CD4 T cells from HIV-infected adults.\n"
],
"offsets": [
[
0,
1279
]
]
}
] | [
{
"id": "PMID-9119999_T1",
"type": "Protein",
"text": [
"CD4"
],
"offsets": [
[
32,
35
]
],
"normalized": []
},
{
"id": "PMID-9119999_T2",
"type": "Protein",
"text": [
"CD28"
],
"offsets": [
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64,
68
]
],
"normalized": []
},
{
"id": "PMID-9119999_T3",
"type": "Protein",
"text": [
"CD4"
],
"offsets": [
[
173,
176
]
],
"normalized": []
},
{
"id": "PMID-9119999_T4",
"type": "Protein",
"text": [
"CD28"
],
"offsets": [
[
221,
225
]
],
"normalized": []
},
{
"id": "PMID-9119999_T5",
"type": "Protein",
"text": [
"CD4"
],
"offsets": [
[
270,
273
]
],
"normalized": []
},
{
"id": "PMID-9119999_T6",
"type": "Protein",
"text": [
"PHA"
],
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[
360,
363
]
],
"normalized": []
},
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"id": "PMID-9119999_T7",
"type": "Protein",
"text": [
"CD4"
],
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513,
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]
],
"normalized": []
},
{
"id": "PMID-9119999_T8",
"type": "Protein",
"text": [
"CD45RA"
],
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[
558,
564
]
],
"normalized": []
},
{
"id": "PMID-9119999_T9",
"type": "Protein",
"text": [
"CD62L"
],
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[
569,
574
]
],
"normalized": []
},
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"id": "PMID-9119999_T10",
"type": "Protein",
"text": [
"CD4"
],
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1241,
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]
],
"normalized": []
},
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"id": "PMID-9119999_T11",
"type": "Entity",
"text": [
"CD3"
],
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60,
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]
],
"normalized": []
},
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"id": "PMID-9119999_T12",
"type": "Entity",
"text": [
"CD3"
],
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[
213,
216
]
],
"normalized": []
},
{
"id": "PMID-9119999_T13",
"type": "Entity",
"text": [
"nuclear factor-kappaB"
],
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[
962,
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]
],
"normalized": []
},
{
"id": "PMID-9119999_T14",
"type": "Entity",
"text": [
"activator protein-1"
],
"offsets": [
[
988,
1007
]
],
"normalized": []
}
] | [] | [] | [] |
139 | PMID-7641319 | [
{
"id": "PMID-7641319__text",
"type": "abstract",
"text": [
"Characterization of 5' end of human thromboxane receptor gene. Organizational analysis and mapping of protein kinase C--responsive elements regulating expression in platelets. \nPlatelet thromboxane receptors are acutely and reversibly upregulated after acute myocardial infarction. To determine if platelet thromboxane receptors are under transcriptional control, we isolated and characterized human genomic DNA clones containing the 5' flanking region of the thromboxane receptor gene. The exon-intron structure of the 5' portion of the thromboxane receptor gene was determined initially by comparing the nucleotide sequence of the 5' flanking genomic clone with that of a novel human uterine thromboxane receptor cDNA that extended the mRNA 141 bp further upstream than the previously identified human placental cDNA. A major transcription initiation site was located in three human tissues approximately 560 bp upstream from the translation initiation codon and 380 bp upstream from any previously identified transcription initiation site. The thromboxane receptor gene has neither a TATA nor a CAAT consensus site. Promoter function of the 5' flanking region of the thromboxane receptor gene was evaluated by transfection of thromboxane receptor gene promoter/chloramphenicol acetyltransferase (CAT) chimera plasmids into platelet-like K562 cells. Thromboxane receptor promoter activity, as assessed by CAT expression, was relatively weak but was significantly enhanced by phorbol ester treatment. Functional analysis of 5' deletion constructs in transfected K562 cells and gel mobility shift localized the major phorbol ester-responsive motifs in the thromboxane receptor gene promoter to a cluster of activator protein-2 (AP-2) binding consensus sites located approximately 1.8 kb 5' from the transcription initiation site. These studies are the first to determine the structure and organization of the 5' end of the thromboxane receptor gene and demonstrate that thromboxane receptor gene expression can be regulated by activation of protein kinase C via induction of an AP-2-like nuclear factor binding to upstream promoter elements. These findings strongly suggest that the mechanism for previously described upregulation of platelet thromboxane receptors after acute myocardial infarction is increased thromboxane receptor gene transcription in platelet-progenitor cells.\n"
],
"offsets": [
[
0,
2382
]
]
}
] | [
{
"id": "PMID-7641319_T1",
"type": "Protein",
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"thromboxane receptor"
],
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[
36,
56
]
],
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},
{
"id": "PMID-7641319_T2",
"type": "Protein",
"text": [
"thromboxane receptors"
],
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[
186,
207
]
],
"normalized": []
},
{
"id": "PMID-7641319_T3",
"type": "Protein",
"text": [
"thromboxane receptors"
],
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307,
328
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},
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"id": "PMID-7641319_T4",
"type": "Protein",
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],
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},
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"id": "PMID-7641319_T5",
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"id": "PMID-7641319_T6",
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"id": "PMID-7641319_T8",
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},
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"id": "PMID-7641319_T9",
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},
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"id": "PMID-7641319_T10",
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],
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},
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"id": "PMID-7641319_T11",
"type": "Protein",
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"CAT"
],
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],
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},
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"id": "PMID-7641319_T12",
"type": "Protein",
"text": [
"Thromboxane receptor"
],
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1352,
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],
"normalized": []
},
{
"id": "PMID-7641319_T13",
"type": "Protein",
"text": [
"CAT"
],
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[
1407,
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]
],
"normalized": []
},
{
"id": "PMID-7641319_T14",
"type": "Protein",
"text": [
"thromboxane receptor"
],
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[
1656,
1676
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],
"normalized": []
},
{
"id": "PMID-7641319_T15",
"type": "Protein",
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"thromboxane receptor"
],
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},
{
"id": "PMID-7641319_T16",
"type": "Protein",
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"thromboxane receptor"
],
"offsets": [
[
1970,
1990
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],
"normalized": []
},
{
"id": "PMID-7641319_T17",
"type": "Protein",
"text": [
"thromboxane receptors"
],
"offsets": [
[
2243,
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],
"normalized": []
},
{
"id": "PMID-7641319_T18",
"type": "Protein",
"text": [
"thromboxane receptor"
],
"offsets": [
[
2312,
2332
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],
"normalized": []
},
{
"id": "PMID-7641319_T19",
"type": "Entity",
"text": [
"protein kinase C--responsive elements"
],
"offsets": [
[
102,
139
]
],
"normalized": []
},
{
"id": "PMID-7641319_T20",
"type": "Entity",
"text": [
"protein kinase C"
],
"offsets": [
[
102,
118
]
],
"normalized": []
},
{
"id": "PMID-7641319_T21",
"type": "Entity",
"text": [
"human genomic DNA clones"
],
"offsets": [
[
394,
418
]
],
"normalized": []
},
{
"id": "PMID-7641319_T22",
"type": "Entity",
"text": [
"5' flanking region"
],
"offsets": [
[
434,
452
]
],
"normalized": []
},
{
"id": "PMID-7641319_T23",
"type": "Entity",
"text": [
"exon-intron structure"
],
"offsets": [
[
491,
512
]
],
"normalized": []
},
{
"id": "PMID-7641319_T24",
"type": "Entity",
"text": [
"5' portion"
],
"offsets": [
[
520,
530
]
],
"normalized": []
},
{
"id": "PMID-7641319_T25",
"type": "Entity",
"text": [
"nucleotide sequence"
],
"offsets": [
[
606,
625
]
],
"normalized": []
},
{
"id": "PMID-7641319_T26",
"type": "Entity",
"text": [
"141 bp further upstream"
],
"offsets": [
[
743,
766
]
],
"normalized": []
},
{
"id": "PMID-7641319_T27",
"type": "Entity",
"text": [
"transcription initiation site"
],
"offsets": [
[
828,
857
]
],
"normalized": []
},
{
"id": "PMID-7641319_T28",
"type": "Entity",
"text": [
"560 bp upstream"
],
"offsets": [
[
907,
922
]
],
"normalized": []
},
{
"id": "PMID-7641319_T29",
"type": "Entity",
"text": [
"translation initiation codon"
],
"offsets": [
[
932,
960
]
],
"normalized": []
},
{
"id": "PMID-7641319_T30",
"type": "Entity",
"text": [
"380 bp upstream"
],
"offsets": [
[
965,
980
]
],
"normalized": []
},
{
"id": "PMID-7641319_T31",
"type": "Entity",
"text": [
"transcription initiation site"
],
"offsets": [
[
1012,
1041
]
],
"normalized": []
},
{
"id": "PMID-7641319_T32",
"type": "Entity",
"text": [
"TATA"
],
"offsets": [
[
1087,
1091
]
],
"normalized": []
},
{
"id": "PMID-7641319_T33",
"type": "Entity",
"text": [
"CAAT consensus site"
],
"offsets": [
[
1098,
1117
]
],
"normalized": []
},
{
"id": "PMID-7641319_T34",
"type": "Entity",
"text": [
"5' flanking region"
],
"offsets": [
[
1144,
1162
]
],
"normalized": []
},
{
"id": "PMID-7641319_T35",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
1373,
1381
]
],
"normalized": []
},
{
"id": "PMID-7641319_T36",
"type": "Entity",
"text": [
"major phorbol ester-responsive motifs"
],
"offsets": [
[
1611,
1648
]
],
"normalized": []
},
{
"id": "PMID-7641319_T37",
"type": "Entity",
"text": [
"activator protein-2 (AP-2) binding consensus sites"
],
"offsets": [
[
1707,
1757
]
],
"normalized": []
},
{
"id": "PMID-7641319_T38",
"type": "Entity",
"text": [
"activator protein-2"
],
"offsets": [
[
1707,
1726
]
],
"normalized": []
},
{
"id": "PMID-7641319_T39",
"type": "Entity",
"text": [
"AP-2"
],
"offsets": [
[
1728,
1732
]
],
"normalized": []
},
{
"id": "PMID-7641319_T40",
"type": "Entity",
"text": [
"transcription initiation site"
],
"offsets": [
[
1799,
1828
]
],
"normalized": []
},
{
"id": "PMID-7641319_T41",
"type": "Entity",
"text": [
"protein kinase C"
],
"offsets": [
[
2041,
2057
]
],
"normalized": []
},
{
"id": "PMID-7641319_T42",
"type": "Entity",
"text": [
"AP-2"
],
"offsets": [
[
2078,
2082
]
],
"normalized": []
},
{
"id": "PMID-7641319_T43",
"type": "Entity",
"text": [
"upstream promoter elements"
],
"offsets": [
[
2114,
2140
]
],
"normalized": []
}
] | [] | [
{
"id": "PMID-7641319_1",
"entity_ids": [
"PMID-7641319_T10",
"PMID-7641319_T11"
]
}
] | [
{
"id": "PMID-7641319_R1",
"type": "Protein-Component",
"arg1_id": "PMID-7641319_T4",
"arg2_id": "PMID-7641319_T22",
"normalized": []
},
{
"id": "PMID-7641319_R2",
"type": "Protein-Component",
"arg1_id": "PMID-7641319_T5",
"arg2_id": "PMID-7641319_T23",
"normalized": []
},
{
"id": "PMID-7641319_R3",
"type": "Protein-Component",
"arg1_id": "PMID-7641319_T5",
"arg2_id": "PMID-7641319_T24",
"normalized": []
},
{
"id": "PMID-7641319_R4",
"type": "Protein-Component",
"arg1_id": "PMID-7641319_T7",
"arg2_id": "PMID-7641319_T33",
"normalized": []
},
{
"id": "PMID-7641319_R5",
"type": "Protein-Component",
"arg1_id": "PMID-7641319_T7",
"arg2_id": "PMID-7641319_T32",
"normalized": []
},
{
"id": "PMID-7641319_R6",
"type": "Protein-Component",
"arg1_id": "PMID-7641319_T8",
"arg2_id": "PMID-7641319_T34",
"normalized": []
},
{
"id": "PMID-7641319_R7",
"type": "Protein-Component",
"arg1_id": "PMID-7641319_T12",
"arg2_id": "PMID-7641319_T35",
"normalized": []
},
{
"id": "PMID-7641319_R8",
"type": "Protein-Component",
"arg1_id": "PMID-7641319_T14",
"arg2_id": "PMID-7641319_T36",
"normalized": []
}
] |
140 | PMID-9697844 | [
{
"id": "PMID-9697844__text",
"type": "abstract",
"text": [
"Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function. \nMyD88, originally isolated as a myeloid differentiation primary response gene, is shown to act as an adaptor in interleukin-1 (IL-1) signaling by interacting with both the IL-1 receptor complex and IL-1 receptor-associated kinase (IRAK). Mice generated by gene targeting to lack MyD88 have defects in T cell proliferation as well as induction of acute phase proteins and cytokines in response to IL-1. Increases in interferon-gamma production and natural killer cell activity in response to IL-18 are abrogated. In vivo Th1 response is also impaired. Furthermore, IL-18-induced activation of NF-kappaB and c-Jun N-terminal kinase (JNK) is blocked in MyD88-/- Th1-developing cells. Taken together, these results demonstrate that MyD88 is a critical component in the signaling cascade that is mediated by IL-1 receptor as well as IL-18 receptor.\n"
],
"offsets": [
[
0,
937
]
]
}
] | [
{
"id": "PMID-9697844_T1",
"type": "Protein",
"text": [
"MyD88"
],
"offsets": [
[
27,
32
]
],
"normalized": []
},
{
"id": "PMID-9697844_T2",
"type": "Protein",
"text": [
"IL-18"
],
"offsets": [
[
67,
72
]
],
"normalized": []
},
{
"id": "PMID-9697844_T3",
"type": "Protein",
"text": [
"MyD88"
],
"offsets": [
[
93,
98
]
],
"normalized": []
},
{
"id": "PMID-9697844_T4",
"type": "Protein",
"text": [
"MyD88"
],
"offsets": [
[
372,
377
]
],
"normalized": []
},
{
"id": "PMID-9697844_T5",
"type": "Protein",
"text": [
"IL-18"
],
"offsets": [
[
584,
589
]
],
"normalized": []
},
{
"id": "PMID-9697844_T6",
"type": "Protein",
"text": [
"IL-18"
],
"offsets": [
[
657,
662
]
],
"normalized": []
},
{
"id": "PMID-9697844_T7",
"type": "Protein",
"text": [
"MyD88"
],
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"id": "PMID-9697844_T8",
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],
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"id": "PMID-9697844_T9",
"type": "Protein",
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"id": "PMID-9697844_T10",
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"myeloid differentiation primary response gene"
],
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125,
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"id": "PMID-9697844_T11",
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],
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265,
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"id": "PMID-9697844_T12",
"type": "Entity",
"text": [
"NF-kappaB"
],
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685,
694
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}
] | [] | [] | [] |
141 | PMID-1668145 | [
{
"id": "PMID-1668145__text",
"type": "abstract",
"text": [
"Every enhancer works with every promoter for all the combinations tested: could new regulatory pathways evolve by enhancer shuffling? \nThe promoters and enhancers of cell type-specific genes are often conserved in evolution, and hence one might expect that a given enhancer has evolved to work best with its own promoter. While this expectation may be realized in some cases, we have not found evidence for it. A total of 27 combinations of different promoters and enhancers were tested by transfection into cultured cells. We found that the relative efficiency of the enhancers is approximately the same, irrespective of the type of promoter used, i.e., there was no strong preference for any given enhancer/promoter combination. Notably, we do not see particularly strong transcription when the immunoglobulin kappa enhancer (or the immunoglobulin heavy chain enhancer) is used to activate a kappa gene promoter. We propose that a generally permissive enhancer/promoter interaction is of evolutionary benefit for higher eukaryotes: by enhancer shuffling, genes could be easily brought under a new type of inducibility/cell type specificity.\n"
],
"offsets": [
[
0,
1143
]
]
}
] | [
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"id": "PMID-1668145_T1",
"type": "Entity",
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"enhancer"
],
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6,
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"id": "PMID-1668145_T2",
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"id": "PMID-1668145_T3",
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"id": "PMID-1668145_T4",
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"id": "PMID-1668145_T5",
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"enhancers"
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153,
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"id": "PMID-1668145_T6",
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265,
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]
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"id": "PMID-1668145_T7",
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],
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304,
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],
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"genes"
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}
] | [] | [] | [] |
142 | PMID-8504932 | [
{
"id": "PMID-8504932__text",
"type": "abstract",
"text": [
"Ectopic expression of a conditional GATA-2/estrogen receptor chimera arrests erythroid differentiation in a hormone-dependent manner. \nThe GATA factors are a family of transcriptional regulatory proteins in eukaryotes that share extensive homology in their DNA-binding domains. One enigmatic aspect of GATA factor expression is that several GATA proteins, which ostensibly share the same DNA-binding site specificity, are coexpressed in erythroid cells. To elucidate the roles of individual GATA factors in erythropoiesis, conditional alleles of GATA-1, GATA-2, and GATA-3 were prepared by fusing each of the factors to the hormone-binding domain of the human estrogen receptor (ER). These GATA/ER chimeric factors were shown to be hormone-inducible trans-activating proteins in transient transfection assays. When stably introduced into primary erythroblasts or conditionally transformed erythroid progenitors cells, exogenous GATA-2/ER promoted proliferation and inhibited terminal differentiation in an estrogen-dependent manner. These phenotypic effects are specifically attributable to the action of ectopically expressed GATA-2/ER because erythroblasts expressing exogenous GATA-2 are constitutively arrested in differentiation and because erythroid progenitors expressing either Gal/ER or GATA-3/ER do not display a hormone-responsive block in differentiation. Thus, the GATA-2 transcription factor appears to play a role in regulating the self-renewal capacity of early erythroid progenitor cells.\n"
],
"offsets": [
[
0,
1506
]
]
}
] | [
{
"id": "PMID-8504932_T1",
"type": "Protein",
"text": [
"GATA-2"
],
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[
36,
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]
],
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},
{
"id": "PMID-8504932_T2",
"type": "Protein",
"text": [
"estrogen receptor"
],
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43,
60
]
],
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},
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"id": "PMID-8504932_T3",
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],
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546,
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],
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},
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"id": "PMID-8504932_T4",
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],
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},
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"id": "PMID-8504932_T5",
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"id": "PMID-8504932_T6",
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"text": [
"estrogen receptor"
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],
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},
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"id": "PMID-8504932_T7",
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"ER"
],
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]
],
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},
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"id": "PMID-8504932_T8",
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"id": "PMID-8504932_T9",
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},
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"id": "PMID-8504932_T10",
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},
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"id": "PMID-8504932_T11",
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},
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"id": "PMID-8504932_T12",
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},
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"id": "PMID-8504932_T14",
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"id": "PMID-8504932_T16",
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"id": "PMID-8504932_T17",
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],
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},
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"id": "PMID-8504932_T18",
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"DNA-binding domains"
],
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257,
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]
],
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},
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"id": "PMID-8504932_T19",
"type": "Entity",
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],
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388,
404
]
],
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},
{
"id": "PMID-8504932_T20",
"type": "Entity",
"text": [
"hormone-binding domain"
],
"offsets": [
[
624,
646
]
],
"normalized": []
}
] | [] | [
{
"id": "PMID-8504932_1",
"entity_ids": [
"PMID-8504932_T6",
"PMID-8504932_T7"
]
}
] | [
{
"id": "PMID-8504932_R1",
"type": "Protein-Component",
"arg1_id": "PMID-8504932_T6",
"arg2_id": "PMID-8504932_T20",
"normalized": []
}
] |
143 | PMID-8843413 | [
{
"id": "PMID-8843413__text",
"type": "abstract",
"text": [
"Transcriptional control of steroid-regulated apoptosis in murine thymoma cells. \nEarly studies in murine T cell lines indicated that transcriptional transactivation functions encoded in the glucocorticoid receptor (GR) N-terminal domain are required for glucocorticoid-mediated apoptosis. However, more recent studies in human T cell lines have suggested that the N-terminal domain is not necessary for steroid-regulated apoptosis and that GR-mediated transrepression may be the more critical mechanism. To better understand the contribution of the GR N-terminal transactivation domain in mediating murine thymocyte apoptosis, we stably transfected GR, GR variants, and the androgen receptor (AR) into receptor-negative S49 murine thymoma cells. GR expression levels were shown to be rate-limiting for initiating the apoptotic pathway, and a positive correlation between steroid sensitivity and GR-mediated induction of an integrated mouse mammary tumor virus (MMTV) LTR reporter gene was observed. Analysis of GR chimeric receptors containing the potent VP16 and E1A viral transactivation domains in place of the GR N terminus revealed that even low level expression of these receptors resulted in both enhanced steroid sensitivity and MMTV induction, thus supporting a role for transactivation in apoptosis. In contrast, we found that AR can initiate apoptosis in S49 cells after treatment with 5 alpha-dihydrotestosterone, despite its relative inability to induce high level expression of MMTV. To investigate this further, we examined the steroid-regulated expression of an endogenous thymocyte-specific gene called GIG18. We found that GIG18 was rapidly induced to comparable levels by both AR and GR, demonstrating that AR can indeed function as a transcriptional activator in S49 cells and, moreover, that GIG18 induction may be a marker of early apoptotic events in steroid-treated cells. Taken together, these results support our conclusion that transcriptional transactivation is a necessary signaling component of S49 cell apoptosis, although an additional role for GR-mediated transrepression cannot be excluded.\n"
],
"offsets": [
[
0,
2125
]
]
}
] | [
{
"id": "PMID-8843413_T1",
"type": "Protein",
"text": [
"glucocorticoid receptor"
],
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[
190,
213
]
],
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},
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"id": "PMID-8843413_T2",
"type": "Protein",
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"GR"
],
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[
215,
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]
],
"normalized": []
},
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"id": "PMID-8843413_T3",
"type": "Protein",
"text": [
"GR"
],
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440,
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]
],
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},
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"id": "PMID-8843413_T4",
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},
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},
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653,
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]
],
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},
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"id": "PMID-8843413_T7",
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"androgen receptor"
],
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674,
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]
],
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},
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},
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},
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"id": "PMID-8843413_T12",
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"VP16"
],
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]
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},
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"id": "PMID-8843413_T13",
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"E1A"
],
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},
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},
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],
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"id": "PMID-8843413_T18",
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},
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},
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"id": "PMID-8843413_T21",
"type": "Protein",
"text": [
"GIG18"
],
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1813,
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},
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"id": "PMID-8843413_T22",
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"GR"
],
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[
2077,
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},
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"id": "PMID-8843413_T23",
"type": "Entity",
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"glucocorticoid receptor (GR) N-terminal domain"
],
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190,
236
]
],
"normalized": []
},
{
"id": "PMID-8843413_T24",
"type": "Entity",
"text": [
"N-terminal domain"
],
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364,
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],
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},
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"id": "PMID-8843413_T25",
"type": "Entity",
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],
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552,
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]
],
"normalized": []
},
{
"id": "PMID-8843413_T26",
"type": "Entity",
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"mouse mammary tumor virus (MMTV) LTR reporter gene"
],
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[
934,
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]
],
"normalized": []
},
{
"id": "PMID-8843413_T27",
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"text": [
"viral transactivation domains"
],
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[
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],
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},
{
"id": "PMID-8843413_T28",
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"N terminus"
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},
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"id": "PMID-8843413_T29",
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"id": "PMID-8843413_T30",
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},
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"id": "PMID-8843413_T31",
"type": "Entity",
"text": [
"thymocyte-specific gene"
],
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1589,
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}
] | [] | [
{
"id": "PMID-8843413_1",
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]
},
{
"id": "PMID-8843413_2",
"entity_ids": [
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}
] | [
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},
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},
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"type": "Protein-Component",
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},
{
"id": "PMID-8843413_R4",
"type": "Protein-Component",
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},
{
"id": "PMID-8843413_R5",
"type": "Protein-Component",
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"arg2_id": "PMID-8843413_T27",
"normalized": []
}
] |
144 | PMID-9115366 | [
{
"id": "PMID-9115366__text",
"type": "abstract",
"text": [
"A novel genetic system to isolate a dominant negative effector on DNA-binding activity of Oct-2. \nRecent studies have revealed that interactions between transcription factors play an important role in regulation of gene expression in eukaryotic cells. To isolate cDNA clones that dominantly inhibit the DNA-binding activity of Oct-2, chosen as a representative factor, we have developed a novel screening system. This employs an Escherichia coli tester strain carrying a modified lac operon as a reporter gene, with the lac operator sequence replaced by an octamer sequence. Oct-2 expressed in this tester strain represses the expression of the reporter gene and changes the phenotype of the cell from Lac+to Lac-. Introduction of a cDNA expression library prepared from a human T-cell line into the Oct-2-harboring tester strain allowed selection of three Lac+clones out of 1 x 10(5) transformants. One of them, hT86, encoding a putative zinc finger protein was found to derepress beta-galactosidase activity in the Oct-2-harboring tester strain at the transcriptional level. In gel mobility shift assays, hT86 attenuated the intensity of the retarded band composed of the octamer probe and Oct-2, suggesting a dominant negative effect on the DNA-binding activity of Oct-2. The strategy described here provides a new approach for studying protein-protein interactions that govern the complex regulation of gene expression.\n"
],
"offsets": [
[
0,
1424
]
]
}
] | [
{
"id": "PMID-9115366_T1",
"type": "Protein",
"text": [
"Oct-2"
],
"offsets": [
[
90,
95
]
],
"normalized": []
},
{
"id": "PMID-9115366_T2",
"type": "Protein",
"text": [
"Oct-2"
],
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327,
332
]
],
"normalized": []
},
{
"id": "PMID-9115366_T3",
"type": "Protein",
"text": [
"Oct-2"
],
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575,
580
]
],
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},
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"id": "PMID-9115366_T4",
"type": "Protein",
"text": [
"Oct-2"
],
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800,
805
]
],
"normalized": []
},
{
"id": "PMID-9115366_T5",
"type": "Protein",
"text": [
"beta-galactosidase"
],
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[
982,
1000
]
],
"normalized": []
},
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"id": "PMID-9115366_T6",
"type": "Protein",
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"Oct-2"
],
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1017,
1022
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],
"normalized": []
},
{
"id": "PMID-9115366_T7",
"type": "Protein",
"text": [
"Oct-2"
],
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1192,
1197
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],
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},
{
"id": "PMID-9115366_T8",
"type": "Protein",
"text": [
"Oct-2"
],
"offsets": [
[
1268,
1273
]
],
"normalized": []
},
{
"id": "PMID-9115366_T9",
"type": "Entity",
"text": [
"cDNA clones"
],
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[
263,
274
]
],
"normalized": []
},
{
"id": "PMID-9115366_T10",
"type": "Entity",
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],
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471,
490
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},
{
"id": "PMID-9115366_T11",
"type": "Entity",
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"reporter gene"
],
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496,
509
]
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},
{
"id": "PMID-9115366_T12",
"type": "Entity",
"text": [
"octamer sequence"
],
"offsets": [
[
557,
573
]
],
"normalized": []
}
] | [] | [] | [] |
145 | PMID-10428853 | [
{
"id": "PMID-10428853__text",
"type": "abstract",
"text": [
"Tissue-specific regulation of the ecto-5'-nucleotidase promoter. Role of the camp response element site in mediating repression by the upstream regulatory region. \nWe have isolated the 5' region of the ecto-5'-nucleotidase (low K(m) 5'-NT) gene and established that a 969-base pair (bp) fragment confers cell-specific expression of a CAT reporter gene that correlates with the expression of endogenous ecto-5'-NT mRNA and enzymatic activity. A 768-bp upstream negative regulatory region has been identified that conferred lymphocyte-specific negative regulation in a heterologous system with a 244-bp deoxycytidine kinase core promoter. DNase I footprinting identified several protected areas including Sp1, Sp1/AP-2, and cAMP response element (CRE) binding sites within the 201-bp core promoter region and Sp1, NRE-2a, TCF-1/LEF-1, and Sp1/NF-AT binding sites in the upstream regulatory region. Whereas the CRE site was essential in mediating the negative activity of the upstream regulatory region in Jurkat but not in HeLa cells, mutation of the Sp1/AP-2 site decreased promoter activity in both cell lines. Electrophoretic mobility shift assay analysis of proteins binding to the CRE site identified both ATF-1 and ATF-2 in Jurkat cells. Finally, phorbol 12-myristate 13-acetate increased the activity of both the core and the 969-bp promoter fragments, and this increase was abrogated by mutations at the CRE site. In summary, we have identified a tissue-specific regulatory region 5' of the ecto-5'-NT core promoter that requires the presence of a functional CRE site within the basal promoter for its suppressive activity.\n"
],
"offsets": [
[
0,
1630
]
]
}
] | [
{
"id": "PMID-10428853_T1",
"type": "Protein",
"text": [
"ecto-5'-nucleotidase"
],
"offsets": [
[
34,
54
]
],
"normalized": []
},
{
"id": "PMID-10428853_T2",
"type": "Protein",
"text": [
"ecto-5'-nucleotidase"
],
"offsets": [
[
202,
222
]
],
"normalized": []
},
{
"id": "PMID-10428853_T3",
"type": "Protein",
"text": [
"5'-NT"
],
"offsets": [
[
233,
238
]
],
"normalized": []
},
{
"id": "PMID-10428853_T4",
"type": "Protein",
"text": [
"CAT"
],
"offsets": [
[
334,
337
]
],
"normalized": []
},
{
"id": "PMID-10428853_T5",
"type": "Protein",
"text": [
"ecto-5'-NT"
],
"offsets": [
[
402,
412
]
],
"normalized": []
},
{
"id": "PMID-10428853_T6",
"type": "Protein",
"text": [
"DNase I"
],
"offsets": [
[
637,
644
]
],
"normalized": []
},
{
"id": "PMID-10428853_T7",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
703,
706
]
],
"normalized": []
},
{
"id": "PMID-10428853_T8",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
708,
711
]
],
"normalized": []
},
{
"id": "PMID-10428853_T9",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
807,
810
]
],
"normalized": []
},
{
"id": "PMID-10428853_T10",
"type": "Protein",
"text": [
"NRE-2a"
],
"offsets": [
[
812,
818
]
],
"normalized": []
},
{
"id": "PMID-10428853_T11",
"type": "Protein",
"text": [
"TCF-1"
],
"offsets": [
[
820,
825
]
],
"normalized": []
},
{
"id": "PMID-10428853_T12",
"type": "Protein",
"text": [
"LEF-1"
],
"offsets": [
[
826,
831
]
],
"normalized": []
},
{
"id": "PMID-10428853_T13",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
837,
840
]
],
"normalized": []
},
{
"id": "PMID-10428853_T14",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
1049,
1052
]
],
"normalized": []
},
{
"id": "PMID-10428853_T15",
"type": "Protein",
"text": [
"ATF-1"
],
"offsets": [
[
1209,
1214
]
],
"normalized": []
},
{
"id": "PMID-10428853_T16",
"type": "Protein",
"text": [
"ATF-2"
],
"offsets": [
[
1219,
1224
]
],
"normalized": []
},
{
"id": "PMID-10428853_T17",
"type": "Protein",
"text": [
"ecto-5'-NT"
],
"offsets": [
[
1497,
1507
]
],
"normalized": []
},
{
"id": "PMID-10428853_T18",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
55,
63
]
],
"normalized": []
},
{
"id": "PMID-10428853_T19",
"type": "Entity",
"text": [
"camp response element site"
],
"offsets": [
[
77,
103
]
],
"normalized": []
},
{
"id": "PMID-10428853_T20",
"type": "Entity",
"text": [
"upstream regulatory region"
],
"offsets": [
[
135,
161
]
],
"normalized": []
},
{
"id": "PMID-10428853_T21",
"type": "Entity",
"text": [
"5' region"
],
"offsets": [
[
185,
194
]
],
"normalized": []
},
{
"id": "PMID-10428853_T22",
"type": "Entity",
"text": [
"reporter gene"
],
"offsets": [
[
338,
351
]
],
"normalized": []
},
{
"id": "PMID-10428853_T23",
"type": "Entity",
"text": [
"768-bp upstream negative regulatory region"
],
"offsets": [
[
444,
486
]
],
"normalized": []
},
{
"id": "PMID-10428853_T24",
"type": "Entity",
"text": [
"244-bp deoxycytidine kinase core promoter"
],
"offsets": [
[
594,
635
]
],
"normalized": []
},
{
"id": "PMID-10428853_T25",
"type": "Entity",
"text": [
"binding sites"
],
"offsets": [
[
750,
763
]
],
"normalized": []
},
{
"id": "PMID-10428853_T26",
"type": "Entity",
"text": [
"binding sites"
],
"offsets": [
[
847,
860
]
],
"normalized": []
},
{
"id": "PMID-10428853_T27",
"type": "Entity",
"text": [
"upstream regulatory region"
],
"offsets": [
[
868,
894
]
],
"normalized": []
},
{
"id": "PMID-10428853_T28",
"type": "Entity",
"text": [
"CRE site"
],
"offsets": [
[
908,
916
]
],
"normalized": []
},
{
"id": "PMID-10428853_T29",
"type": "Entity",
"text": [
"upstream regulatory region"
],
"offsets": [
[
973,
999
]
],
"normalized": []
},
{
"id": "PMID-10428853_T30",
"type": "Entity",
"text": [
"/AP-2 site"
],
"offsets": [
[
1052,
1062
]
],
"normalized": []
},
{
"id": "PMID-10428853_T31",
"type": "Entity",
"text": [
"CRE site"
],
"offsets": [
[
1184,
1192
]
],
"normalized": []
},
{
"id": "PMID-10428853_T32",
"type": "Entity",
"text": [
"969-bp promoter fragments"
],
"offsets": [
[
1331,
1356
]
],
"normalized": []
},
{
"id": "PMID-10428853_T33",
"type": "Entity",
"text": [
"CRE site"
],
"offsets": [
[
1410,
1418
]
],
"normalized": []
},
{
"id": "PMID-10428853_T34",
"type": "Entity",
"text": [
"tissue-specific regulatory region"
],
"offsets": [
[
1453,
1486
]
],
"normalized": []
},
{
"id": "PMID-10428853_T35",
"type": "Entity",
"text": [
"core promoter"
],
"offsets": [
[
1508,
1521
]
],
"normalized": []
},
{
"id": "PMID-10428853_T36",
"type": "Entity",
"text": [
"CRE site"
],
"offsets": [
[
1565,
1573
]
],
"normalized": []
},
{
"id": "PMID-10428853_T37",
"type": "Entity",
"text": [
"basal promoter"
],
"offsets": [
[
1585,
1599
]
],
"normalized": []
}
] | [] | [
{
"id": "PMID-10428853_1",
"entity_ids": [
"PMID-10428853_T11",
"PMID-10428853_T12"
]
}
] | [
{
"id": "PMID-10428853_R1",
"type": "Protein-Component",
"arg1_id": "PMID-10428853_T1",
"arg2_id": "PMID-10428853_T18",
"normalized": []
},
{
"id": "PMID-10428853_R2",
"type": "Protein-Component",
"arg1_id": "PMID-10428853_T2",
"arg2_id": "PMID-10428853_T21",
"normalized": []
},
{
"id": "PMID-10428853_R3",
"type": "Protein-Component",
"arg1_id": "PMID-10428853_T3",
"arg2_id": "PMID-10428853_T21",
"normalized": []
},
{
"id": "PMID-10428853_R4",
"type": "Protein-Component",
"arg1_id": "PMID-10428853_T17",
"arg2_id": "PMID-10428853_T34",
"normalized": []
},
{
"id": "PMID-10428853_R5",
"type": "Protein-Component",
"arg1_id": "PMID-10428853_T17",
"arg2_id": "PMID-10428853_T35",
"normalized": []
}
] |
146 | PMID-2105528 | [
{
"id": "PMID-2105528__text",
"type": "abstract",
"text": [
"Two distinct transcription factors that bind the immunoglobulin enhancer microE5/kappa 2 motif. \nActivity of the immunoglobulin heavy and kappa light chain gene enhancers depends on a complex interplay of ubiquitous and developmentally regulated proteins. Two complementary DNAs were isolated that encode proteins, denoted ITF-1 and ITF-2, that are expressed in a variety of cell types and bind the microE5/kappa 2 motif found in both heavy and kappa light chain enhancers. The complementary DNAs are the products of distinct genes, yet both ITF-1 and ITF-2 are structurally and functionally similar. The two proteins interact with one another through their putative helix-loop-helix motifs and each possesses a distinct domain that dictates transcription activation.\n"
],
"offsets": [
[
0,
768
]
]
}
] | [
{
"id": "PMID-2105528_T1",
"type": "Protein",
"text": [
"ITF-1"
],
"offsets": [
[
323,
328
]
],
"normalized": []
},
{
"id": "PMID-2105528_T2",
"type": "Protein",
"text": [
"ITF-2"
],
"offsets": [
[
333,
338
]
],
"normalized": []
},
{
"id": "PMID-2105528_T3",
"type": "Protein",
"text": [
"ITF-1"
],
"offsets": [
[
542,
547
]
],
"normalized": []
},
{
"id": "PMID-2105528_T4",
"type": "Protein",
"text": [
"ITF-2"
],
"offsets": [
[
552,
557
]
],
"normalized": []
},
{
"id": "PMID-2105528_T5",
"type": "Entity",
"text": [
"immunoglobulin enhancer"
],
"offsets": [
[
49,
72
]
],
"normalized": []
},
{
"id": "PMID-2105528_T6",
"type": "Entity",
"text": [
"microE5/kappa 2 motif"
],
"offsets": [
[
73,
94
]
],
"normalized": []
},
{
"id": "PMID-2105528_T7",
"type": "Entity",
"text": [
"chain gene enhancers"
],
"offsets": [
[
150,
170
]
],
"normalized": []
},
{
"id": "PMID-2105528_T8",
"type": "Entity",
"text": [
"complementary DNAs"
],
"offsets": [
[
260,
278
]
],
"normalized": []
},
{
"id": "PMID-2105528_T9",
"type": "Entity",
"text": [
"microE5/kappa 2 motif"
],
"offsets": [
[
399,
420
]
],
"normalized": []
},
{
"id": "PMID-2105528_T10",
"type": "Entity",
"text": [
"chain enhancers"
],
"offsets": [
[
457,
472
]
],
"normalized": []
},
{
"id": "PMID-2105528_T11",
"type": "Entity",
"text": [
"complementary DNAs"
],
"offsets": [
[
478,
496
]
],
"normalized": []
},
{
"id": "PMID-2105528_T12",
"type": "Entity",
"text": [
"distinct genes"
],
"offsets": [
[
517,
531
]
],
"normalized": []
},
{
"id": "PMID-2105528_T13",
"type": "Entity",
"text": [
"helix-loop-helix motifs"
],
"offsets": [
[
667,
690
]
],
"normalized": []
},
{
"id": "PMID-2105528_T14",
"type": "Entity",
"text": [
"distinct domain"
],
"offsets": [
[
712,
727
]
],
"normalized": []
}
] | [] | [] | [] |
147 | PMID-2112575 | [
{
"id": "PMID-2112575__text",
"type": "abstract",
"text": [
"The expression of c-fos, c-jun, and c-myc genes is regulated by heat shock in human lymphoid cells. \nThe effect of heat shock on the expression of the nuclear protooncogenes c-fos, c-jun, and c-myc was studied in human lymphoid cells. Heat shock caused an increase in c-fos and c-jun mRNA levels and a decrease in c-myc mRNA levels in pre-B (Hyon) and T (DND-41) cell lines as well as in freshly isolated normal human thymocytes. The changes in the mRNA levels of these protooncogenes in Hyon cells were most pronounced at 42 and 43 degrees C; kinetic analysis demonstrated that the changes could be detected within 30 min of heat shock. Altered transcription of c-fos and c-myc genes was the primary effect of heat shock. Secondarily, heat shock of Hyon cells stabilized the c-myc mRNA level by increasing its half-life from 24 to 45 min. The overall effect of heat shock on c-myc mRNA level, however, was a marked inhibition of its transcription. These results demonstrate that the transcription of nuclear protooncogenes is regulated by heat shock indicating a role for nuclear protooncogenes in the stress response of lymphoid cells.\n"
],
"offsets": [
[
0,
1138
]
]
}
] | [
{
"id": "PMID-2112575_T1",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
18,
23
]
],
"normalized": []
},
{
"id": "PMID-2112575_T2",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
25,
30
]
],
"normalized": []
},
{
"id": "PMID-2112575_T3",
"type": "Protein",
"text": [
"c-myc"
],
"offsets": [
[
36,
41
]
],
"normalized": []
},
{
"id": "PMID-2112575_T4",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
174,
179
]
],
"normalized": []
},
{
"id": "PMID-2112575_T5",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
181,
186
]
],
"normalized": []
},
{
"id": "PMID-2112575_T6",
"type": "Protein",
"text": [
"c-myc"
],
"offsets": [
[
192,
197
]
],
"normalized": []
},
{
"id": "PMID-2112575_T7",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
268,
273
]
],
"normalized": []
},
{
"id": "PMID-2112575_T8",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
278,
283
]
],
"normalized": []
},
{
"id": "PMID-2112575_T9",
"type": "Protein",
"text": [
"c-myc"
],
"offsets": [
[
314,
319
]
],
"normalized": []
},
{
"id": "PMID-2112575_T10",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
663,
668
]
],
"normalized": []
},
{
"id": "PMID-2112575_T11",
"type": "Protein",
"text": [
"c-myc"
],
"offsets": [
[
673,
678
]
],
"normalized": []
},
{
"id": "PMID-2112575_T12",
"type": "Protein",
"text": [
"c-myc"
],
"offsets": [
[
776,
781
]
],
"normalized": []
},
{
"id": "PMID-2112575_T13",
"type": "Protein",
"text": [
"c-myc"
],
"offsets": [
[
876,
881
]
],
"normalized": []
},
{
"id": "PMID-2112575_T14",
"type": "Entity",
"text": [
"nuclear protooncogenes"
],
"offsets": [
[
151,
173
]
],
"normalized": []
},
{
"id": "PMID-2112575_T15",
"type": "Entity",
"text": [
"protooncogenes"
],
"offsets": [
[
470,
484
]
],
"normalized": []
},
{
"id": "PMID-2112575_T16",
"type": "Entity",
"text": [
"nuclear protooncogenes"
],
"offsets": [
[
1001,
1023
]
],
"normalized": []
},
{
"id": "PMID-2112575_T17",
"type": "Entity",
"text": [
"nuclear protooncogenes"
],
"offsets": [
[
1073,
1095
]
],
"normalized": []
}
] | [] | [] | [] |
148 | PMID-8649822 | [
{
"id": "PMID-8649822__text",
"type": "abstract",
"text": [
"Identification of a human LIM-Hox gene, hLH-2, aberrantly expressed in chronic myelogenous leukaemia and located on 9q33-34.1. \nWe describe the isolation of human LH-2, a putative transcription factor containing two cysteine-rich regions (LIM domains) and a homeobox (Hox) DNA-binding domain. High levels of hLH-2 expression were observed in all cases of chronic myelogenous leukaemia (CML) tested, regardless of disease status. hLH-2 was mapped to chromosome 9Q33-34.1, in the same region as the reciprocal translocation that creates the BCR-ABL chimera of the Philadelphia chromosome (Ph'), the hallmark of CML; hLH-2 was retained on the derivative 9 chromosome and is therefore centromeric of c-ABL. The proximity of hLH-2 to the breakpoint on chromosome 9 raises the possibility of cis-activation by the t(9;22)(q34;q11) translocation. In addition to finding hLH-2 expression in all cases of CML, expression was observed in lymphoid malignancies and myeloid cell lines, but not in primary cases of acute myelogenous leukaemia. The role of hLH-2 in the development or progression of leukaemia is not known. However, hLH-2 may prove useful as a marker of CML for monitoring residual disease.\n"
],
"offsets": [
[
0,
1194
]
]
}
] | [
{
"id": "PMID-8649822_T1",
"type": "Protein",
"text": [
"hLH-2"
],
"offsets": [
[
40,
45
]
],
"normalized": []
},
{
"id": "PMID-8649822_T2",
"type": "Protein",
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"LH-2"
],
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[
163,
167
]
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},
{
"id": "PMID-8649822_T3",
"type": "Protein",
"text": [
"hLH-2"
],
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[
308,
313
]
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},
{
"id": "PMID-8649822_T4",
"type": "Protein",
"text": [
"hLH-2"
],
"offsets": [
[
429,
434
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"normalized": []
},
{
"id": "PMID-8649822_T5",
"type": "Protein",
"text": [
"BCR"
],
"offsets": [
[
539,
542
]
],
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},
{
"id": "PMID-8649822_T6",
"type": "Protein",
"text": [
"ABL"
],
"offsets": [
[
543,
546
]
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},
{
"id": "PMID-8649822_T7",
"type": "Protein",
"text": [
"hLH-2"
],
"offsets": [
[
614,
619
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],
"normalized": []
},
{
"id": "PMID-8649822_T8",
"type": "Protein",
"text": [
"c-ABL"
],
"offsets": [
[
696,
701
]
],
"normalized": []
},
{
"id": "PMID-8649822_T9",
"type": "Protein",
"text": [
"hLH-2"
],
"offsets": [
[
720,
725
]
],
"normalized": []
},
{
"id": "PMID-8649822_T10",
"type": "Protein",
"text": [
"hLH-2"
],
"offsets": [
[
863,
868
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],
"normalized": []
},
{
"id": "PMID-8649822_T11",
"type": "Protein",
"text": [
"hLH-2"
],
"offsets": [
[
1043,
1048
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],
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},
{
"id": "PMID-8649822_T12",
"type": "Protein",
"text": [
"hLH-2"
],
"offsets": [
[
1119,
1124
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],
"normalized": []
},
{
"id": "PMID-8649822_T13",
"type": "Entity",
"text": [
"human LIM-Hox gene"
],
"offsets": [
[
20,
38
]
],
"normalized": []
},
{
"id": "PMID-8649822_T14",
"type": "Entity",
"text": [
"9q33-34.1"
],
"offsets": [
[
116,
125
]
],
"normalized": []
},
{
"id": "PMID-8649822_T15",
"type": "Entity",
"text": [
"cysteine-rich regions"
],
"offsets": [
[
216,
237
]
],
"normalized": []
},
{
"id": "PMID-8649822_T16",
"type": "Entity",
"text": [
"cysteine"
],
"offsets": [
[
216,
224
]
],
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},
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"id": "PMID-8649822_T17",
"type": "Entity",
"text": [
"LIM domains"
],
"offsets": [
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239,
250
]
],
"normalized": []
},
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"id": "PMID-8649822_T18",
"type": "Entity",
"text": [
"homeobox (Hox) DNA-binding domain"
],
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258,
291
]
],
"normalized": []
},
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"id": "PMID-8649822_T19",
"type": "Entity",
"text": [
"chromosome 9Q33-34.1"
],
"offsets": [
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449,
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]
],
"normalized": []
},
{
"id": "PMID-8649822_T20",
"type": "Entity",
"text": [
"t(9;22)(q34;q11)"
],
"offsets": [
[
808,
824
]
],
"normalized": []
}
] | [] | [] | [] |
149 | PMID-1984449 | [
{
"id": "PMID-1984449__text",
"type": "abstract",
"text": [
"Induction of NF-KB during monocyte differentiation by HIV type 1 infection. \nThe production of human immunodeficiency virus type 1 (HIV-1) progeny was followed in the U937 promonocytic cell line after stimulation either with retinoic acid or PMA, and in purified human monocytes and macrophages. Electrophoretic mobility shift assays and Southwestern blotting experiments were used to detect the binding of cellular transactivation factor NF-KB to the double repeat-KB enhancer sequence located in the long terminal repeat. PMA treatment, and not retinoic acid treatment of the U937 cells acts in inducing NF-KB expression in the nuclei. In nuclear extracts from monocytes or macrophages, induction of NF-KB occurred only if the cells were previously infected with HIV-1. When U937 cells were infected with HIV-1, no induction of NF-KB factor was detected, whereas high level of progeny virions was produced, suggesting that this factor was not required for viral replication. These results indicate that in monocytic cell lineage, HIV-1 could mimic some differentiation/activation stimuli allowing nuclear NF-KB expression.\n"
],
"offsets": [
[
0,
1125
]
]
}
] | [
{
"id": "PMID-1984449_T1",
"type": "Entity",
"text": [
"NF-KB"
],
"offsets": [
[
439,
444
]
],
"normalized": []
},
{
"id": "PMID-1984449_T2",
"type": "Entity",
"text": [
"double repeat-KB enhancer sequence"
],
"offsets": [
[
452,
486
]
],
"normalized": []
},
{
"id": "PMID-1984449_T3",
"type": "Entity",
"text": [
"long terminal repeat"
],
"offsets": [
[
502,
522
]
],
"normalized": []
}
] | [] | [] | [] |
150 | PMID-8605587 | [
{
"id": "PMID-8605587__text",
"type": "abstract",
"text": [
"Soluble tumor necrosis factor receptors inhibit phorbol myristate acetate and cytokine-induced HIV-1 expression chronically infected U1 cells. \nRecombinant human tumor necrosis factor (TNF) binding protein-1 (r-h TBP-1) and recombinant human soluble dimeric TNF receptor (rhu TNFR:Fc) were used to determine the relative contributions of TNF to phorbol myristate acetate (PMA) and cytokine-induced human immunodeficiency virus type 1 (HIV-1) replication in chronically infected cell lines. Treatment of HIV-1-infected promonocytic U1 cells with r-h-TBP-1 or rhu TNFR:Fc reduced PMA-induced HIV-1 p24 antigen production in a concentration-dependent manner, with a maximal inhibition of approximately 90%. Maximal inhibition of p24 antigen production in T-lymphocytic ACH-2 cells was 47% with r-hTBP-1 and 42% with rhu TNFR:Fc. r-hTBP-1 and rhu TNFR:Fc also decreased p24 antigen synthesized by U1 cells in response to other stimuli, including phytohemagglutinin (PHA)-induced supernatant, granulocyte-macrophage colony-stimulating factor, interleukin-6, and TNF. Addition of r-hTBP-1 to U1 cells during the last 4 h of a 24 h incubation with PMA still inhibited p24 antigen production by 15%. U1 cells stimulated with 10(-7) M PMA released approximately 1 ng/ml endogenous TBP-1 with an initial peak observed at 1 h and a second peak at 24 h after PMA stimulation. r-hTBP-1 also partially reversed inhibition of U1 cellular proliferation caused by PMA. Both r-hTBP-1 and rhu TNFR:Fc blocked PMA induction of nuclear factor (NK)- kappa B DNA-binding activity in U1 cells in association with decreases in HIV-1 replication. We conclude that soluble TNF receptors can inhibit stimuli-induced HIV-1 expression and NK- kappa B DNA-binding activity in chronically infected U1 cells.\n"
],
"offsets": [
[
0,
1776
]
]
}
] | [
{
"id": "PMID-8605587_T1",
"type": "Protein",
"text": [
"p24"
],
"offsets": [
[
596,
599
]
],
"normalized": []
},
{
"id": "PMID-8605587_T2",
"type": "Protein",
"text": [
"p24"
],
"offsets": [
[
726,
729
]
],
"normalized": []
},
{
"id": "PMID-8605587_T3",
"type": "Protein",
"text": [
"p24"
],
"offsets": [
[
866,
869
]
],
"normalized": []
},
{
"id": "PMID-8605587_T4",
"type": "Protein",
"text": [
"granulocyte-macrophage colony-stimulating factor"
],
"offsets": [
[
988,
1036
]
],
"normalized": []
},
{
"id": "PMID-8605587_T5",
"type": "Protein",
"text": [
"interleukin-6"
],
"offsets": [
[
1038,
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]
],
"normalized": []
},
{
"id": "PMID-8605587_T6",
"type": "Protein",
"text": [
"p24"
],
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[
1161,
1164
]
],
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},
{
"id": "PMID-8605587_T7",
"type": "Protein",
"text": [
"TBP-1"
],
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[
1272,
1277
]
],
"normalized": []
},
{
"id": "PMID-8605587_T8",
"type": "Entity",
"text": [
"nuclear factor (NK)- kappa B"
],
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[
1507,
1535
]
],
"normalized": []
},
{
"id": "PMID-8605587_T9",
"type": "Entity",
"text": [
"HIV-1"
],
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1688,
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]
],
"normalized": []
},
{
"id": "PMID-8605587_T10",
"type": "Entity",
"text": [
"NK- kappa B"
],
"offsets": [
[
1709,
1720
]
],
"normalized": []
}
] | [] | [] | [] |
151 | PMID-9341877 | [
{
"id": "PMID-9341877__text",
"type": "abstract",
"text": [
"The spatial distribution of human immunoglobulin genes within the nucleus: evidence for gene topography independent of cell type and transcriptional activity. \nThe three-dimensional positioning of immunoglobulin (Ig) genes within the nucleus of human cells was investigated using in situ hybridization and confocal microscopy. The visualization of heavy and light chain genes in B-lymphoid cells showed that the three Ig genes are differentially and nonrandomly distributed in different nuclear subvolumes: the kappa genes were found to be preferentially confined to an outer nuclear volume, whereas the gamma and lambda genes consistently occupied more central positions within the nucleus, the lambda genes being more interior when compared with the gamma genes. The data further show that these overall topographical distributions are independent of gene transcriptional activity and are conserved in different cell types. Although subtle gene movements within those defined topographical regions cannot be excluded by this study, the results indicate that tissue specificity of gene expression is not accompanied by drastic changes in gene nuclear topography, rather suggesting that gene organization within the nucleus may be primarily dependent on structural constraints imposed on the respective chromosomes.\n"
],
"offsets": [
[
0,
1316
]
]
}
] | [
{
"id": "PMID-9341877_T1",
"type": "Entity",
"text": [
"human immunoglobulin genes"
],
"offsets": [
[
28,
54
]
],
"normalized": []
},
{
"id": "PMID-9341877_T2",
"type": "Entity",
"text": [
"immunoglobulin (Ig) genes"
],
"offsets": [
[
197,
222
]
],
"normalized": []
},
{
"id": "PMID-9341877_T3",
"type": "Entity",
"text": [
"chain genes"
],
"offsets": [
[
364,
375
]
],
"normalized": []
},
{
"id": "PMID-9341877_T4",
"type": "Entity",
"text": [
"Ig genes"
],
"offsets": [
[
418,
426
]
],
"normalized": []
},
{
"id": "PMID-9341877_T5",
"type": "Entity",
"text": [
"kappa genes"
],
"offsets": [
[
511,
522
]
],
"normalized": []
},
{
"id": "PMID-9341877_T6",
"type": "Entity",
"text": [
"gamma"
],
"offsets": [
[
604,
609
]
],
"normalized": []
},
{
"id": "PMID-9341877_T7",
"type": "Entity",
"text": [
"lambda genes"
],
"offsets": [
[
614,
626
]
],
"normalized": []
},
{
"id": "PMID-9341877_T8",
"type": "Entity",
"text": [
"lambda genes"
],
"offsets": [
[
696,
708
]
],
"normalized": []
},
{
"id": "PMID-9341877_T9",
"type": "Entity",
"text": [
"gamma genes"
],
"offsets": [
[
752,
763
]
],
"normalized": []
}
] | [] | [] | [] |
152 | PMID-9442400 | [
{
"id": "PMID-9442400__text",
"type": "abstract",
"text": [
"Expression of transcription factor genes after influenza A virus infection. \nInfection of human monocytes with influenza A virus induces a broad range of proinflammatory cytokines and mononuclear cell attracting chemokines before the infected cells undergo apoptosis. The underlying mechanisms by which the corresponding genes are transcriptionally initiated after virus infection are still poorly understood. Activation of NF-kappa B seems to play an important role in the regulation of many proinflammatory cytokine genes, but cannot be the only mechanism, since several cytokine genes lack respective binding sites in their promoter regions. Therefore, we additionally investigated other transcription factors of possible importance such as CREB, CTF, OTF-1, and OTF-2. To explore long-term regulatory mechanisms, we investigated the induction of transcription factors on the gene expression level which may be important to substitute for metabolized transcription factor proteins after their activation. We identified a cell-type-specific differential response: CREB, CTF, OTF-1, OFT-2, and NF-kappa B genes were strongly induced 1 to 4 hours after influenza A virus infection in the monocytic cell line Mono Mac 6, while in freshly prepared human monocytes no significant changes were detected. In infected monocytes, which die by apoptosis, the expression of CREB, CTF, and OTF-2 was rather suppressed 8 hours after infection. In conclusion, the long-term regulation of transcription factor gene expression in non-proliferating cells seems to be of minor importance after influenza infection since in apoptosisprone cells an immediate availability of transcription factor proteins is required.\n"
],
"offsets": [
[
0,
1700
]
]
}
] | [
{
"id": "PMID-9442400_T1",
"type": "Protein",
"text": [
"CTF"
],
"offsets": [
[
750,
753
]
],
"normalized": []
},
{
"id": "PMID-9442400_T2",
"type": "Protein",
"text": [
"OTF-1"
],
"offsets": [
[
755,
760
]
],
"normalized": []
},
{
"id": "PMID-9442400_T3",
"type": "Protein",
"text": [
"OTF-2"
],
"offsets": [
[
766,
771
]
],
"normalized": []
},
{
"id": "PMID-9442400_T4",
"type": "Protein",
"text": [
"CTF"
],
"offsets": [
[
1072,
1075
]
],
"normalized": []
},
{
"id": "PMID-9442400_T5",
"type": "Protein",
"text": [
"OTF-1"
],
"offsets": [
[
1077,
1082
]
],
"normalized": []
},
{
"id": "PMID-9442400_T6",
"type": "Protein",
"text": [
"OFT-2"
],
"offsets": [
[
1084,
1089
]
],
"normalized": []
},
{
"id": "PMID-9442400_T7",
"type": "Protein",
"text": [
"CTF"
],
"offsets": [
[
1371,
1374
]
],
"normalized": []
},
{
"id": "PMID-9442400_T8",
"type": "Protein",
"text": [
"OTF-2"
],
"offsets": [
[
1380,
1385
]
],
"normalized": []
},
{
"id": "PMID-9442400_T9",
"type": "Entity",
"text": [
"transcription factor genes"
],
"offsets": [
[
14,
40
]
],
"normalized": []
},
{
"id": "PMID-9442400_T10",
"type": "Entity",
"text": [
"corresponding genes"
],
"offsets": [
[
307,
326
]
],
"normalized": []
},
{
"id": "PMID-9442400_T11",
"type": "Entity",
"text": [
"NF-kappa B"
],
"offsets": [
[
424,
434
]
],
"normalized": []
},
{
"id": "PMID-9442400_T12",
"type": "Entity",
"text": [
"proinflammatory cytokine genes"
],
"offsets": [
[
493,
523
]
],
"normalized": []
},
{
"id": "PMID-9442400_T13",
"type": "Entity",
"text": [
"cytokine genes"
],
"offsets": [
[
573,
587
]
],
"normalized": []
},
{
"id": "PMID-9442400_T14",
"type": "Entity",
"text": [
"binding sites"
],
"offsets": [
[
604,
617
]
],
"normalized": []
},
{
"id": "PMID-9442400_T15",
"type": "Entity",
"text": [
"promoter regions"
],
"offsets": [
[
627,
643
]
],
"normalized": []
}
] | [] | [] | [] |
153 | PMID-9835626 | [
{
"id": "PMID-9835626__text",
"type": "abstract",
"text": [
"In vitro suppression of programmed cell death of B cells by tissue inhibitor of metalloproteinases-1. \nCellular pathways for induction of programmed cell death (PCD) have been identified, but little is known about specific extracellular matrix processes that may affect apoptosis along those pathways. In this study, a series of Burkitt's lymphoma (BL) cell lines were assayed for their expression of tissue inhibitor of metalloproteinases (TIMP)-1. Results indicate that TIMP-1-positive BL lines show resistance to cold-shock-induced apoptosis. Furthermore, recombinant TIMP-1, but not TIMP-2 or a synthetic metalloproteinase inhibitor (BB-94), confers resistance to apoptosis induced by both CD95-dependent and -independent (cold shock, serum deprivation, and gamma-radiation) pathways in TIMP-1-negative BL lines. TIMP-1 suppression of PCD is not due to metalloproteinase inhibition, as reduction and alkylation of the TIMP-1 did not abolish this activity. Retroviral induction of TIMP-1 not only resulted in cell survival but also in continued DNA synthesis for up to 5 d in the absence of serum, while controls underwent apoptosis. This resistance to apoptosis is reversed by anti-TIMP-1 antibodies, demonstrating that secreted TIMP-1 is active in blocking apoptosis. Furthermore, TIMP-1 upregulation induced expression of Bcl-XL but not Bcl-2 as well as decreased NF-kappaB activity as compared with controls. These results demonstrate that TIMP-1 suppresses apoptosis in B cells and suggests a novel activity for TIMP-1 in tissue homeostasis.\n"
],
"offsets": [
[
0,
1550
]
]
}
] | [
{
"id": "PMID-9835626_T1",
"type": "Protein",
"text": [
"tissue inhibitor of metalloproteinases-1"
],
"offsets": [
[
60,
100
]
],
"normalized": []
},
{
"id": "PMID-9835626_T2",
"type": "Protein",
"text": [
"tissue inhibitor of metalloproteinases (TIMP)-1"
],
"offsets": [
[
401,
448
]
],
"normalized": []
},
{
"id": "PMID-9835626_T3",
"type": "Protein",
"text": [
"TIMP-1"
],
"offsets": [
[
472,
478
]
],
"normalized": []
},
{
"id": "PMID-9835626_T4",
"type": "Protein",
"text": [
"TIMP-1"
],
"offsets": [
[
571,
577
]
],
"normalized": []
},
{
"id": "PMID-9835626_T5",
"type": "Protein",
"text": [
"TIMP-2"
],
"offsets": [
[
587,
593
]
],
"normalized": []
},
{
"id": "PMID-9835626_T6",
"type": "Protein",
"text": [
"CD95"
],
"offsets": [
[
694,
698
]
],
"normalized": []
},
{
"id": "PMID-9835626_T7",
"type": "Protein",
"text": [
"TIMP-1"
],
"offsets": [
[
791,
797
]
],
"normalized": []
},
{
"id": "PMID-9835626_T8",
"type": "Protein",
"text": [
"TIMP-1"
],
"offsets": [
[
817,
823
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],
"normalized": []
},
{
"id": "PMID-9835626_T9",
"type": "Protein",
"text": [
"TIMP-1"
],
"offsets": [
[
922,
928
]
],
"normalized": []
},
{
"id": "PMID-9835626_T10",
"type": "Protein",
"text": [
"TIMP-1"
],
"offsets": [
[
984,
990
]
],
"normalized": []
},
{
"id": "PMID-9835626_T11",
"type": "Protein",
"text": [
"TIMP-1"
],
"offsets": [
[
1186,
1192
]
],
"normalized": []
},
{
"id": "PMID-9835626_T12",
"type": "Protein",
"text": [
"TIMP-1"
],
"offsets": [
[
1233,
1239
]
],
"normalized": []
},
{
"id": "PMID-9835626_T13",
"type": "Protein",
"text": [
"TIMP-1"
],
"offsets": [
[
1286,
1292
]
],
"normalized": []
},
{
"id": "PMID-9835626_T14",
"type": "Protein",
"text": [
"Bcl-XL"
],
"offsets": [
[
1328,
1334
]
],
"normalized": []
},
{
"id": "PMID-9835626_T15",
"type": "Protein",
"text": [
"Bcl-2"
],
"offsets": [
[
1343,
1348
]
],
"normalized": []
},
{
"id": "PMID-9835626_T16",
"type": "Protein",
"text": [
"TIMP-1"
],
"offsets": [
[
1447,
1453
]
],
"normalized": []
},
{
"id": "PMID-9835626_T17",
"type": "Protein",
"text": [
"TIMP-1"
],
"offsets": [
[
1520,
1526
]
],
"normalized": []
},
{
"id": "PMID-9835626_T18",
"type": "Entity",
"text": [
"NF-kappaB"
],
"offsets": [
[
1370,
1379
]
],
"normalized": []
}
] | [] | [] | [] |
154 | PMID-2121746 | [
{
"id": "PMID-2121746__text",
"type": "abstract",
"text": [
"Adherence-dependent increase in human monocyte PDGF(B) mRNA is associated with increases in c-fos, c-jun, and EGR2 mRNA. \nAdherence is an important initial step in the transition of a circulating monocyte to a tissue macrophage. This differentiation is accompanied by an augmented capacity to generate growth factors. We hypothesized that adherence itself might be an important trigger for a sequence of gene activation culminating in cells with increased mRNA encoding profibrotic growth factors such as platelet-derived growth factor B subunit (PDGF[B]) and transforming growth factor-beta (TGF-beta). After in vitro adherence, human monocytes had a biphasic increase in PDGF(B) mRNA with peaks at 6 h and 13 d. No increase in TGF-beta mRNA was observed. The 6-h increase in PDGF(B) mRNA was adherence dependent, and in addition, was abrogated when the cytoskeletal integrity was compromised by cytochalasin D. The 6-h increase in PDGF(B) mRNA was unaltered by adherence in the presence of the monocyte stimulus lipopolysaccharide. Adherence to either fibronectin or collagen-coated plastic had little consistent effect on PDGF(B) mRNA accumulation. The increased PDGF(B) mRNA observed in adherent monocytes was accompanied by increases in mRNAs of the early growth response genes c-fos (maximal at 20 min), c-jun, and EGR2 (maximal at 6-24 h). The increase in c-jun and EGR2, but not c-fos, mRNA was also abrogated by cytochalasin D. These observations suggest that adherence results in increases of c-fos, c-jun, EGR2, and PDGF(B) mRNA. In addition, the increases in c-jun, EGR2, and PDGF(B) may depend on cytoskeletal rearrangement. Modulation of these events at the time of adherence offers a mechanism by which differential priming of the cells may be accomplished.\n"
],
"offsets": [
[
0,
1773
]
]
}
] | [
{
"id": "PMID-2121746_T1",
"type": "Protein",
"text": [
"PDGF(B)"
],
"offsets": [
[
47,
54
]
],
"normalized": []
},
{
"id": "PMID-2121746_T2",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
92,
97
]
],
"normalized": []
},
{
"id": "PMID-2121746_T3",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
99,
104
]
],
"normalized": []
},
{
"id": "PMID-2121746_T4",
"type": "Protein",
"text": [
"EGR2"
],
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[
110,
114
]
],
"normalized": []
},
{
"id": "PMID-2121746_T5",
"type": "Protein",
"text": [
"platelet-derived growth factor B subunit"
],
"offsets": [
[
505,
545
]
],
"normalized": []
},
{
"id": "PMID-2121746_T6",
"type": "Protein",
"text": [
"PDGF[B]"
],
"offsets": [
[
547,
554
]
],
"normalized": []
},
{
"id": "PMID-2121746_T7",
"type": "Protein",
"text": [
"transforming growth factor-beta"
],
"offsets": [
[
560,
591
]
],
"normalized": []
},
{
"id": "PMID-2121746_T8",
"type": "Protein",
"text": [
"TGF-beta"
],
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[
593,
601
]
],
"normalized": []
},
{
"id": "PMID-2121746_T9",
"type": "Protein",
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"PDGF(B)"
],
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[
673,
680
]
],
"normalized": []
},
{
"id": "PMID-2121746_T10",
"type": "Protein",
"text": [
"TGF-beta"
],
"offsets": [
[
729,
737
]
],
"normalized": []
},
{
"id": "PMID-2121746_T11",
"type": "Protein",
"text": [
"PDGF(B)"
],
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[
777,
784
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],
"normalized": []
},
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"id": "PMID-2121746_T12",
"type": "Protein",
"text": [
"PDGF(B)"
],
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[
933,
940
]
],
"normalized": []
},
{
"id": "PMID-2121746_T13",
"type": "Protein",
"text": [
"fibronectin"
],
"offsets": [
[
1054,
1065
]
],
"normalized": []
},
{
"id": "PMID-2121746_T14",
"type": "Protein",
"text": [
"PDGF(B)"
],
"offsets": [
[
1125,
1132
]
],
"normalized": []
},
{
"id": "PMID-2121746_T15",
"type": "Protein",
"text": [
"PDGF(B)"
],
"offsets": [
[
1166,
1173
]
],
"normalized": []
},
{
"id": "PMID-2121746_T16",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
1283,
1288
]
],
"normalized": []
},
{
"id": "PMID-2121746_T17",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
1310,
1315
]
],
"normalized": []
},
{
"id": "PMID-2121746_T18",
"type": "Protein",
"text": [
"EGR2"
],
"offsets": [
[
1321,
1325
]
],
"normalized": []
},
{
"id": "PMID-2121746_T19",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
1363,
1368
]
],
"normalized": []
},
{
"id": "PMID-2121746_T20",
"type": "Protein",
"text": [
"EGR2"
],
"offsets": [
[
1373,
1377
]
],
"normalized": []
},
{
"id": "PMID-2121746_T21",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
1387,
1392
]
],
"normalized": []
},
{
"id": "PMID-2121746_T22",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
1503,
1508
]
],
"normalized": []
},
{
"id": "PMID-2121746_T23",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
1510,
1515
]
],
"normalized": []
},
{
"id": "PMID-2121746_T24",
"type": "Protein",
"text": [
"EGR2"
],
"offsets": [
[
1517,
1521
]
],
"normalized": []
},
{
"id": "PMID-2121746_T25",
"type": "Protein",
"text": [
"PDGF(B)"
],
"offsets": [
[
1527,
1534
]
],
"normalized": []
},
{
"id": "PMID-2121746_T26",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
1571,
1576
]
],
"normalized": []
},
{
"id": "PMID-2121746_T27",
"type": "Protein",
"text": [
"EGR2"
],
"offsets": [
[
1578,
1582
]
],
"normalized": []
},
{
"id": "PMID-2121746_T28",
"type": "Protein",
"text": [
"PDGF(B)"
],
"offsets": [
[
1588,
1595
]
],
"normalized": []
},
{
"id": "PMID-2121746_T29",
"type": "Entity",
"text": [
"early growth response genes"
],
"offsets": [
[
1255,
1282
]
],
"normalized": []
}
] | [] | [
{
"id": "PMID-2121746_1",
"entity_ids": [
"PMID-2121746_T5",
"PMID-2121746_T6"
]
},
{
"id": "PMID-2121746_2",
"entity_ids": [
"PMID-2121746_T7",
"PMID-2121746_T8"
]
}
] | [] |
155 | PMID-8973354 | [
{
"id": "PMID-8973354__text",
"type": "abstract",
"text": [
"Characterization of the murine cyclin-dependent kinase inhibitor gene p27Kip1. \nThe cyclin-dependent kinase inhibitor p27Kip1 plays an important role in regulating cell-cycle progression. p27Kip1 directly inhibits the catalytic activity of cyclin/cdks (cyclin-dependent kinase) complexes and/or interferes physically with cyclin/cdks activation by CAK. Interestingly, the expression level of p27Kip1 mRNA was maximal in resting Go T-cells and rapidly declined following anti-CD3 activation. We report here the cloning of p27Kip1 gene from murine genomic DNA and the functional analysis of the promoter of the p27Kip1 gene. The gene consists of at least three exons and spans more than 5.6 kb of DNA. Primer extension and nuclease S1 protection analysis revealed two major transcription initiation sites. The promoter region lacked a TATA box but contained potential binding sites for the transcriptional factors including two Sp1, CRE, Myb and NFkB located at positions -153, -178, -286, -875, and -1011, respectively. To analyze the regulatory mechanisms controlling p27Kip1 gene expression, we characterized the 5'-flanking region from nt -1609 to +178. The -326 to -615 region contained positive regulatory elements.\n"
],
"offsets": [
[
0,
1220
]
]
}
] | [
{
"id": "PMID-8973354_T1",
"type": "Protein",
"text": [
"p27Kip1"
],
"offsets": [
[
70,
77
]
],
"normalized": []
},
{
"id": "PMID-8973354_T2",
"type": "Protein",
"text": [
"p27Kip1"
],
"offsets": [
[
118,
125
]
],
"normalized": []
},
{
"id": "PMID-8973354_T3",
"type": "Protein",
"text": [
"p27Kip1"
],
"offsets": [
[
188,
195
]
],
"normalized": []
},
{
"id": "PMID-8973354_T4",
"type": "Protein",
"text": [
"p27Kip1"
],
"offsets": [
[
392,
399
]
],
"normalized": []
},
{
"id": "PMID-8973354_T5",
"type": "Protein",
"text": [
"p27Kip1"
],
"offsets": [
[
521,
528
]
],
"normalized": []
},
{
"id": "PMID-8973354_T6",
"type": "Protein",
"text": [
"p27Kip1"
],
"offsets": [
[
609,
616
]
],
"normalized": []
},
{
"id": "PMID-8973354_T7",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
926,
929
]
],
"normalized": []
},
{
"id": "PMID-8973354_T8",
"type": "Protein",
"text": [
"Myb"
],
"offsets": [
[
936,
939
]
],
"normalized": []
},
{
"id": "PMID-8973354_T9",
"type": "Protein",
"text": [
"p27Kip1"
],
"offsets": [
[
1068,
1075
]
],
"normalized": []
},
{
"id": "PMID-8973354_T10",
"type": "Entity",
"text": [
"murine cyclin-dependent kinase inhibitor gene"
],
"offsets": [
[
24,
69
]
],
"normalized": []
},
{
"id": "PMID-8973354_T11",
"type": "Entity",
"text": [
"cyclin-dependent kinase inhibitor"
],
"offsets": [
[
84,
117
]
],
"normalized": []
},
{
"id": "PMID-8973354_T12",
"type": "Entity",
"text": [
"cyclin/cdks (cyclin-dependent kinase) complexes"
],
"offsets": [
[
240,
287
]
],
"normalized": []
},
{
"id": "PMID-8973354_T13",
"type": "Entity",
"text": [
"cyclin/cdks"
],
"offsets": [
[
322,
333
]
],
"normalized": []
},
{
"id": "PMID-8973354_T14",
"type": "Entity",
"text": [
"murine genomic DNA"
],
"offsets": [
[
539,
557
]
],
"normalized": []
},
{
"id": "PMID-8973354_T15",
"type": "Entity",
"text": [
"5.6 kb of DNA"
],
"offsets": [
[
685,
698
]
],
"normalized": []
},
{
"id": "PMID-8973354_T16",
"type": "Entity",
"text": [
"transcription initiation sites"
],
"offsets": [
[
772,
802
]
],
"normalized": []
},
{
"id": "PMID-8973354_T17",
"type": "Entity",
"text": [
"promoter region"
],
"offsets": [
[
808,
823
]
],
"normalized": []
},
{
"id": "PMID-8973354_T18",
"type": "Entity",
"text": [
"TATA box"
],
"offsets": [
[
833,
841
]
],
"normalized": []
},
{
"id": "PMID-8973354_T19",
"type": "Entity",
"text": [
"NFkB"
],
"offsets": [
[
944,
948
]
],
"normalized": []
},
{
"id": "PMID-8973354_T20",
"type": "Entity",
"text": [
"positions -153"
],
"offsets": [
[
960,
974
]
],
"normalized": []
},
{
"id": "PMID-8973354_T21",
"type": "Entity",
"text": [
"-178"
],
"offsets": [
[
976,
980
]
],
"normalized": []
},
{
"id": "PMID-8973354_T22",
"type": "Entity",
"text": [
"-286"
],
"offsets": [
[
982,
986
]
],
"normalized": []
},
{
"id": "PMID-8973354_T23",
"type": "Entity",
"text": [
"-875"
],
"offsets": [
[
988,
992
]
],
"normalized": []
},
{
"id": "PMID-8973354_T24",
"type": "Entity",
"text": [
"-1011"
],
"offsets": [
[
998,
1003
]
],
"normalized": []
},
{
"id": "PMID-8973354_T25",
"type": "Entity",
"text": [
"5'-flanking region"
],
"offsets": [
[
1114,
1132
]
],
"normalized": []
},
{
"id": "PMID-8973354_T26",
"type": "Entity",
"text": [
"nt -1609 to +178"
],
"offsets": [
[
1138,
1154
]
],
"normalized": []
},
{
"id": "PMID-8973354_T27",
"type": "Entity",
"text": [
"-326 to -615 region"
],
"offsets": [
[
1160,
1179
]
],
"normalized": []
},
{
"id": "PMID-8973354_T28",
"type": "Entity",
"text": [
"positive regulatory elements"
],
"offsets": [
[
1190,
1218
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "PMID-8973354_R1",
"type": "Protein-Component",
"arg1_id": "PMID-8973354_T7",
"arg2_id": "PMID-8973354_T21",
"normalized": []
},
{
"id": "PMID-8973354_R2",
"type": "Protein-Component",
"arg1_id": "PMID-8973354_T7",
"arg2_id": "PMID-8973354_T22",
"normalized": []
},
{
"id": "PMID-8973354_R3",
"type": "Protein-Component",
"arg1_id": "PMID-8973354_T7",
"arg2_id": "PMID-8973354_T23",
"normalized": []
},
{
"id": "PMID-8973354_R4",
"type": "Protein-Component",
"arg1_id": "PMID-8973354_T7",
"arg2_id": "PMID-8973354_T24",
"normalized": []
},
{
"id": "PMID-8973354_R5",
"type": "Protein-Component",
"arg1_id": "PMID-8973354_T7",
"arg2_id": "PMID-8973354_T20",
"normalized": []
},
{
"id": "PMID-8973354_R6",
"type": "Protein-Component",
"arg1_id": "PMID-8973354_T8",
"arg2_id": "PMID-8973354_T21",
"normalized": []
},
{
"id": "PMID-8973354_R7",
"type": "Protein-Component",
"arg1_id": "PMID-8973354_T8",
"arg2_id": "PMID-8973354_T22",
"normalized": []
},
{
"id": "PMID-8973354_R8",
"type": "Protein-Component",
"arg1_id": "PMID-8973354_T8",
"arg2_id": "PMID-8973354_T23",
"normalized": []
},
{
"id": "PMID-8973354_R9",
"type": "Protein-Component",
"arg1_id": "PMID-8973354_T8",
"arg2_id": "PMID-8973354_T24",
"normalized": []
},
{
"id": "PMID-8973354_R10",
"type": "Protein-Component",
"arg1_id": "PMID-8973354_T8",
"arg2_id": "PMID-8973354_T20",
"normalized": []
},
{
"id": "PMID-8973354_R11",
"type": "Protein-Component",
"arg1_id": "PMID-8973354_T9",
"arg2_id": "PMID-8973354_T26",
"normalized": []
},
{
"id": "PMID-8973354_R12",
"type": "Protein-Component",
"arg1_id": "PMID-8973354_T9",
"arg2_id": "PMID-8973354_T25",
"normalized": []
}
] |
156 | PMID-2083253 | [
{
"id": "PMID-2083253__text",
"type": "abstract",
"text": [
"Purification of TCF-1 alpha, a T-cell-specific transcription factor that activates the T-cell receptor C alpha gene enhancer in a context-dependent manner. \nThe differentiation of T cells into functionally diverse subpopulations is controlled in part, by transcriptional activation and silencing; however, little is known in detail about the proteins that influence this developmental process. We have purified a new T-cell-specific factor, TCF-1 alpha, that is implicated in the activation of genes encoding a major component of the human T-cell receptor (TCR). TCF-1 alpha, originally identified and purified through its binding sites on the HIV-1 promoter, was found to bind to the TCR alpha enhancer and to promoters for several genes expressed at significantly earlier stages of T-cell development than the TCR alpha gene (e.g., p56lck and CD3 delta). Sequences related to the TCF-1 alpha binding motif (5'-GGCACCCTTTGA-3') are also found in the human TCR delta (and possibly TCR beta) enhancers. Southwestern and gel renaturation experiments with the use of purified protein fractions revealed that TCF-1 alpha activity is derived from a family of 57- to 53-kD proteins that are abundantly expressed in mature and immature T-cell lines (Jurkat, CCRF-CEM) and not in mature B cells (JY, Namalwa) or nonlymphoid (HeLa) cell lines. A small 95-bp fragment of the TCR alpha control region that contains the TCF-1 alpha binding site juxtaposed between a cAMP-response element (the CRE or T alpha 1 motif) and the binding site for a distinct lymphoid-specific protein (TCF-2 alpha) behaved as a potent T-cell-specific enhancer in vivo. Tandem copies of this enhancer functioned synergistically in mature (Jurkat) T-cell lines as well as resting and activated immature (CCRF-CEM) T-cell lines. Mutation of the TCF-1 alpha binding site diminished enhancer activity and disrupted the synergism observed in vivo between tandem enhancer repeats. The TCF-1 alpha binding site was also required for TCR alpha enhancer activity in transcriptionally active extracts from Jurkat but not HeLa cells, confirming that TCF-1 alpha is a T-cell-specific transcription factor. Curiously, the TCF-1 alpha binding element was inactive in vivo when removed from its neighboring elements on the TCR alpha enhancer and positioned in one or more copies upstream of a heterologous promoter. Thus, the transcriptional activity of TCF-1 alpha appears to depend on the TCF-2 alpha and T alpha 1 (CREB) transcription factors and the context of its binding site within the TCR alpha enhancer.\n"
],
"offsets": [
[
0,
2563
]
]
}
] | [
{
"id": "PMID-2083253_T1",
"type": "Protein",
"text": [
"TCF-1 alpha"
],
"offsets": [
[
16,
27
]
],
"normalized": []
},
{
"id": "PMID-2083253_T2",
"type": "Protein",
"text": [
"T-cell receptor C alpha"
],
"offsets": [
[
87,
110
]
],
"normalized": []
},
{
"id": "PMID-2083253_T3",
"type": "Protein",
"text": [
"TCF-1 alpha"
],
"offsets": [
[
441,
452
]
],
"normalized": []
},
{
"id": "PMID-2083253_T4",
"type": "Protein",
"text": [
"TCF-1 alpha"
],
"offsets": [
[
563,
574
]
],
"normalized": []
},
{
"id": "PMID-2083253_T5",
"type": "Protein",
"text": [
"TCR alpha"
],
"offsets": [
[
685,
694
]
],
"normalized": []
},
{
"id": "PMID-2083253_T6",
"type": "Protein",
"text": [
"TCR alpha"
],
"offsets": [
[
812,
821
]
],
"normalized": []
},
{
"id": "PMID-2083253_T7",
"type": "Protein",
"text": [
"p56lck"
],
"offsets": [
[
834,
840
]
],
"normalized": []
},
{
"id": "PMID-2083253_T8",
"type": "Protein",
"text": [
"CD3 delta"
],
"offsets": [
[
845,
854
]
],
"normalized": []
},
{
"id": "PMID-2083253_T9",
"type": "Protein",
"text": [
"TCF-1 alpha"
],
"offsets": [
[
882,
893
]
],
"normalized": []
},
{
"id": "PMID-2083253_T10",
"type": "Protein",
"text": [
"TCR delta"
],
"offsets": [
[
957,
966
]
],
"normalized": []
},
{
"id": "PMID-2083253_T11",
"type": "Protein",
"text": [
"TCR beta"
],
"offsets": [
[
981,
989
]
],
"normalized": []
},
{
"id": "PMID-2083253_T12",
"type": "Protein",
"text": [
"TCF-1 alpha"
],
"offsets": [
[
1105,
1116
]
],
"normalized": []
},
{
"id": "PMID-2083253_T13",
"type": "Protein",
"text": [
"TCR alpha"
],
"offsets": [
[
1365,
1374
]
],
"normalized": []
},
{
"id": "PMID-2083253_T14",
"type": "Protein",
"text": [
"TCF-1 alpha"
],
"offsets": [
[
1408,
1419
]
],
"normalized": []
},
{
"id": "PMID-2083253_T15",
"type": "Protein",
"text": [
"TCF-2 alpha"
],
"offsets": [
[
1568,
1579
]
],
"normalized": []
},
{
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],
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1819
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2000
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2115
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2174,
2185
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2273,
2282
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],
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2404,
2415
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2441,
2452
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2552
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124
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557,
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703
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711,
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"id": "PMID-2083253_T32",
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],
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894,
907
]
],
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},
{
"id": "PMID-2083253_T33",
"type": "Entity",
"text": [
"5'-GGCACCCTTTGA-3'"
],
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909,
927
]
],
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},
{
"id": "PMID-2083253_T34",
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"enhancers"
],
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991,
1000
]
],
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},
{
"id": "PMID-2083253_T35",
"type": "Entity",
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"95-bp fragment"
],
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1343,
1357
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"normalized": []
},
{
"id": "PMID-2083253_T36",
"type": "Entity",
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"control region"
],
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1375,
1389
]
],
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},
{
"id": "PMID-2083253_T37",
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],
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1420,
1432
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},
{
"id": "PMID-2083253_T38",
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],
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1454,
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"id": "PMID-2083253_T39",
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"id": "PMID-2083253_T40",
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"id": "PMID-2083253_T41",
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],
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"id": "PMID-2083253_T42",
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],
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"id": "PMID-2083253_T43",
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"id": "PMID-2083253_T44",
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"id": "PMID-2083253_T45",
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"id": "PMID-2083253_T47",
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"id": "PMID-2083253_T50",
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],
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"id": "PMID-2083253_T51",
"type": "Entity",
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"enhancer"
],
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2553,
2561
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],
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}
] | [] | [
{
"id": "PMID-2083253_1",
"entity_ids": [
"PMID-2083253_T24",
"PMID-2083253_T25"
]
}
] | [
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},
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}
] |
157 | PMID-7888116 | [
{
"id": "PMID-7888116__text",
"type": "abstract",
"text": [
"The regulation of HIV by retinoic acid correlates with cellular expression of the retinoic acid receptors. \nOBJECTIVES: To analyze the effect of retinoic acids (RA) on HIV-1 expression and correlate this effect with expression levels of RA receptors (RARs) in T-lymphoid and monocytoid cell lines. DESIGN AND METHODS: The effect of all-trans and 9-cis RA on HIV-1 production in T-lymphoid (H9, CEM) and monocytoid (U937,THP-1) cell lines was measured during acute and chronic infection. The expression levels of human RAR alpha (hRAR alpha, receptor for all-trans RA) and the human retinoid-X receptor alpha (hRXR alpha receptor for 9-cis RA) were determined by Northern blot analysis. RESULTS: Both all-trans and 9-cis RA inhibited virus replication in HIV-1 IIIB-infected monocytoid cells, in the presence and absence of the co-stimulatory agent phorbol myristate acetate (PMA). The retinoids had weak or no stimulatory effects on HIV production by T-cell lines. HIV production by PMA-stimulated T-cell lines was inhibited by these retinoids. The 9-cis RA was generally more effective than all-trans RA in inhibiting HIV production and in combination generally more effective than the single agents alone. Human RAR alpha was expressed in H9, U937 and THP-1 cells, but almost undetectable in CEM cells. Human RXR alpha was significantly expressed in U937 and THP-1 cells, weakly expressed in H9 cells and not detectable in CEM cells. After stimulation by PMA, RXR alpha expression increased in H9 and U937 cells but not in CEM cells. Human RAR alpha expression was unchanged in H9 and CEM cells, and elevated in U937 cells, after PMA stimulation. CONCLUSION: The effect of RA on HIV-1 expression was cell-type-dependent and partially correlated with cellular expression of RARs. Endogenous or exogenously administered RA may have a significant role in HIV regulation.\n"
],
"offsets": [
[
0,
1870
]
]
}
] | [
{
"id": "PMID-7888116_T1",
"type": "Protein",
"text": [
"RAR alpha"
],
"offsets": [
[
518,
527
]
],
"normalized": []
},
{
"id": "PMID-7888116_T2",
"type": "Protein",
"text": [
"hRAR alpha"
],
"offsets": [
[
529,
539
]
],
"normalized": []
},
{
"id": "PMID-7888116_T3",
"type": "Protein",
"text": [
"retinoid-X receptor alpha"
],
"offsets": [
[
582,
607
]
],
"normalized": []
},
{
"id": "PMID-7888116_T4",
"type": "Protein",
"text": [
"hRXR alpha"
],
"offsets": [
[
609,
619
]
],
"normalized": []
},
{
"id": "PMID-7888116_T5",
"type": "Protein",
"text": [
"RXR alpha"
],
"offsets": [
[
1311,
1320
]
],
"normalized": []
},
{
"id": "PMID-7888116_T6",
"type": "Protein",
"text": [
"RXR alpha"
],
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[
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]
],
"normalized": []
},
{
"id": "PMID-7888116_T7",
"type": "Protein",
"text": [
"RAR alpha"
],
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[
1542,
1551
]
],
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},
{
"id": "PMID-7888116_T8",
"type": "Entity",
"text": [
"HIV-1"
],
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[
168,
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]
],
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},
{
"id": "PMID-7888116_T9",
"type": "Entity",
"text": [
"HIV-1"
],
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[
1681,
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]
],
"normalized": []
}
] | [] | [
{
"id": "PMID-7888116_1",
"entity_ids": [
"PMID-7888116_T1",
"PMID-7888116_T2"
]
}
] | [] |
158 | PMID-2304473 | [
{
"id": "PMID-2304473__text",
"type": "abstract",
"text": [
"The ubiquitous octamer-binding protein(s) is sufficient for transcription of immunoglobulin genes. \nAll immunoglobulin genes contain a conserved octanucleotide promoter element, ATGCAAAT, which has been shown to be required for their normal B-cell-specific transcription. Proteins that bind this octamer have been purified, and cDNAs encoding octamer-binding proteins have been cloned. Some of these proteins (referred to as OTF-2) are lymphoid specific, whereas at least one other, and possibly more (referred to as OTF-1), is found ubiquitously in all cell types. The exact role of these different proteins in directing the tissue-specific expression of immunoglobulin genes is unclear. We have identified two human pre-B-cell lines that contain extremely low levels of OTF-2 yet still express high levels of steady-state immunoglobulin heavy-chain mRNA in vivo and efficiently transcribe an immunoglobulin gene in vitro. Addition of a highly enriched preparation of OTF-1 made from one of these pre-B cells or from HeLa cells specifically stimulated in vitro transcription of an immunoglobulin gene. Furthermore, OFT-1 appeared to have approximately the same transactivation ability as OTF-2 when normalized for binding activity. These results suggest that OTF-1, without OTF-2, is sufficient for transcription of immunoglobulin genes and that OTF-2 alone is not responsible for the B-cell-specific regulation of immunoglobulin gene expression.\n"
],
"offsets": [
[
0,
1448
]
]
}
] | [
{
"id": "PMID-2304473_T1",
"type": "Protein",
"text": [
"OTF-2"
],
"offsets": [
[
425,
430
]
],
"normalized": []
},
{
"id": "PMID-2304473_T2",
"type": "Protein",
"text": [
"OTF-1"
],
"offsets": [
[
517,
522
]
],
"normalized": []
},
{
"id": "PMID-2304473_T3",
"type": "Protein",
"text": [
"OTF-2"
],
"offsets": [
[
772,
777
]
],
"normalized": []
},
{
"id": "PMID-2304473_T4",
"type": "Protein",
"text": [
"OTF-1"
],
"offsets": [
[
969,
974
]
],
"normalized": []
},
{
"id": "PMID-2304473_T5",
"type": "Protein",
"text": [
"OFT-1"
],
"offsets": [
[
1116,
1121
]
],
"normalized": []
},
{
"id": "PMID-2304473_T6",
"type": "Protein",
"text": [
"OTF-2"
],
"offsets": [
[
1189,
1194
]
],
"normalized": []
},
{
"id": "PMID-2304473_T7",
"type": "Protein",
"text": [
"OTF-1"
],
"offsets": [
[
1260,
1265
]
],
"normalized": []
},
{
"id": "PMID-2304473_T8",
"type": "Protein",
"text": [
"OTF-2"
],
"offsets": [
[
1275,
1280
]
],
"normalized": []
},
{
"id": "PMID-2304473_T9",
"type": "Protein",
"text": [
"OTF-2"
],
"offsets": [
[
1347,
1352
]
],
"normalized": []
},
{
"id": "PMID-2304473_T10",
"type": "Entity",
"text": [
"immunoglobulin genes"
],
"offsets": [
[
77,
97
]
],
"normalized": []
},
{
"id": "PMID-2304473_T11",
"type": "Entity",
"text": [
"immunoglobulin genes"
],
"offsets": [
[
104,
124
]
],
"normalized": []
},
{
"id": "PMID-2304473_T12",
"type": "Entity",
"text": [
"octanucleotide promoter element"
],
"offsets": [
[
145,
176
]
],
"normalized": []
},
{
"id": "PMID-2304473_T13",
"type": "Entity",
"text": [
"ATGCAAAT"
],
"offsets": [
[
178,
186
]
],
"normalized": []
},
{
"id": "PMID-2304473_T14",
"type": "Entity",
"text": [
"octamer"
],
"offsets": [
[
296,
303
]
],
"normalized": []
},
{
"id": "PMID-2304473_T15",
"type": "Entity",
"text": [
"cDNAs"
],
"offsets": [
[
328,
333
]
],
"normalized": []
},
{
"id": "PMID-2304473_T16",
"type": "Entity",
"text": [
"immunoglobulin genes"
],
"offsets": [
[
656,
676
]
],
"normalized": []
},
{
"id": "PMID-2304473_T17",
"type": "Entity",
"text": [
"immunoglobulin gene"
],
"offsets": [
[
894,
913
]
],
"normalized": []
},
{
"id": "PMID-2304473_T18",
"type": "Entity",
"text": [
"immunoglobulin gene"
],
"offsets": [
[
1082,
1101
]
],
"normalized": []
},
{
"id": "PMID-2304473_T19",
"type": "Entity",
"text": [
"immunoglobulin genes"
],
"offsets": [
[
1317,
1337
]
],
"normalized": []
},
{
"id": "PMID-2304473_T20",
"type": "Entity",
"text": [
"immunoglobulin gene"
],
"offsets": [
[
1416,
1435
]
],
"normalized": []
}
] | [] | [] | [] |
159 | PMID-9874515 | [
{
"id": "PMID-9874515__text",
"type": "abstract",
"text": [
"X-rays-induced secretion of cellular factor(s) that enhance(s) HIV-1 promoter transcription in various non-irradiated transfected cell lines. \nVarious cellular stress agents like ionizing radiation exposure could activate human immunodeficiency virus type 1 (HIV- 1) replication or reporter gene expression. In addition, extracellular factor(s) released by X-ray-treated human colonic carcinoma cell line (HT29) might activate the long terminal repeat (LTR) of HIV-1 in non-irradiated HT29 cells. In the present report we show that in various transiently or stably transfected cell lines, X-ray irradiation up-regulates HIV-1 LTR transcription through the kappaB regulatory elements. A factor(s), which is processed by and acts upon a variety of cell types, was detected by addition to non-irradiated cells of either X-ray-treated cells or a conditioned medium taken from irradiated cultures. The magnitude of responsiveness is cell type dependent. In addition, X-ray activation of HIV-1 LTR in transiently or stably transfected cell lines is inhibited by a potent antioxidant drug, pyrrolidine dithiocarbamate and by another drug, known for its role in the trapping of growth factors, suramin. The importance of these observations in the pathophysiology of patients with AIDS-related cancers treated by radiotherapy remains to be established.\n"
],
"offsets": [
[
0,
1344
]
]
}
] | [
{
"id": "PMID-9874515_T1",
"type": "Entity",
"text": [
"HIV-1 promoter"
],
"offsets": [
[
63,
77
]
],
"normalized": []
},
{
"id": "PMID-9874515_T2",
"type": "Entity",
"text": [
"reporter gene"
],
"offsets": [
[
282,
295
]
],
"normalized": []
},
{
"id": "PMID-9874515_T3",
"type": "Entity",
"text": [
"long terminal repeat"
],
"offsets": [
[
431,
451
]
],
"normalized": []
},
{
"id": "PMID-9874515_T4",
"type": "Entity",
"text": [
"LTR"
],
"offsets": [
[
453,
456
]
],
"normalized": []
},
{
"id": "PMID-9874515_T5",
"type": "Entity",
"text": [
"HIV-1 LTR"
],
"offsets": [
[
620,
629
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],
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"id": "PMID-9874515_T6",
"type": "Entity",
"text": [
"HIV-1 LTR"
],
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] | [] | [] | [] |
160 | PMID-10089140 | [
{
"id": "PMID-10089140__text",
"type": "abstract",
"text": [
"Reduction of tumour necrosis factor alpha expression and signalling in peripheral blood mononuclear cells from patients with thalassaemia or sickle cell anaemia upon treatment with desferrioxamine. \nRecent evidence indicates that the rate of progression of the HIV-1 disease is significantly reduced in thalassaemia major patients upon treatment with high doses of desferrioxamine (DFX). The authors have previously demonstrated that in vitro exposure of mononuclear cells to DFX decreases the bioavailability of tumour necrosis factor alpha (TNF-alpha) which has a stimulatory effect on HIV-1 replication. In this study, therefore, TNF-alpha bioavailability from mononuclear cells isolated from 10 patients with thalassaemia or sickle cell anaemia given DFX as compared to 10 untreated subjects has been evaluated. Evidence is presented showing that DFX treatment reduces TNF-alpha bioavailability (P<0.05) by inhibiting its steady state (P<0.05) and by enhancing its inactivation through binding to soluble TNF-alpha receptor type II (P<0.05). We also show that DFX treatment limits the in vivo activation of NF-kappaB, a transcription factor involved in both TNF-alpha gene transcription and TNF-alpha signalling (P<0.005). We conclude that TNF-alpha bioavailability and signalling are impaired in patients upon DFX treatment. This mechanism may contribute to delayed progression of the HIV-1 infection in vivo. Copyright 1999 Academic Press.\n"
],
"offsets": [
[
0,
1446
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"id": "PMID-10089140_T1",
"type": "Protein",
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"tumour necrosis factor alpha"
],
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"id": "PMID-10089140_T2",
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"id": "PMID-10089140_T3",
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"id": "PMID-10089140_T4",
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"id": "PMID-10089140_T5",
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"id": "PMID-10089140_T6",
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"id": "PMID-10089140_T7",
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"TNF-alpha"
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"id": "PMID-10089140_T8",
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"id": "PMID-10089140_T9",
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"id": "PMID-10089140_T10",
"type": "Entity",
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"NF-kappaB"
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] | [] | [
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"id": "PMID-10089140_1",
"entity_ids": [
"PMID-10089140_T2",
"PMID-10089140_T3"
]
}
] | [] |
161 | PMID-8184011 | [
{
"id": "PMID-8184011__text",
"type": "abstract",
"text": [
"Activation of nuclear factor kappa B in human lymphoblastoid cells by low-dose ionizing radiation. \nNuclear factor kappa B (NF-kappa B) is a pleiotropic transcription factor which is involved in the transcriptional regulation of several specific genes. Recent reports demonstrated that ionizing radiation in the dose range of 2-50 Gy results in expression of NF-kappa B in human KG-1 myeloid leukemia cells and human B-lymphocyte precursor cells; the precise mechanism involved and the significance are not yet known. The present report demonstrates that even lower doses of ionizing radiation, 0.25-2.0 Gy, are capable of inducing expression of NF-kappa B in EBV-transformed 244B human lymphoblastoid cells. These results are in a dose range where the viability of the cells remains very high. After exposure to 137Cs gamma rays at a dose rate of 1.17 Gy/min, a maximum in expression of NF-kappa B was seen at 8 h after a 0.5-Gy exposure. Time-course studies revealed a biphasic time-dependent expression after 0.5-, 1- and 2-Gy exposures. However, for each time examined, the expression of NF-kappa B was maximum after the 0.5-Gy exposure. The expression of the p50 and p65 NF-kappa B subunits was also shown to be regulated differentially after exposures to 1.0 and 2.0 Gy.\n"
],
"offsets": [
[
0,
1277
]
]
}
] | [
{
"id": "PMID-8184011_T1",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
1164,
1167
]
],
"normalized": []
},
{
"id": "PMID-8184011_T2",
"type": "Protein",
"text": [
"p65"
],
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[
1172,
1175
]
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},
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"id": "PMID-8184011_T3",
"type": "Entity",
"text": [
"nuclear factor kappa B"
],
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[
14,
36
]
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"id": "PMID-8184011_T4",
"type": "Entity",
"text": [
"Nuclear factor kappa B"
],
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[
100,
122
]
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},
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"id": "PMID-8184011_T5",
"type": "Entity",
"text": [
"NF-kappa B"
],
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[
124,
134
]
],
"normalized": []
}
] | [] | [] | [] |
162 | PMID-1454801 | [
{
"id": "PMID-1454801__text",
"type": "abstract",
"text": [
"Transcription of the hypersensitive site HS2 enhancer in erythroid cells. \nIn the human genome, the erythroid-specific hypersensitive site HS2 enhancer regulates the transcription of the downstream beta-like globin genes 10-50 kilobases away. The mechanism of HS2 enhancer function is not known. The present study employs RNA protection assays to analyze the transcriptional status of the HS2 enhancer in transfected recombinant chloramphenicol acetyltransferase (CAT) plasmids. In erythroid K562 cells in which the HS2 enhancer is active, the HS2 sequence directs the synthesis of long enhancer transcripts that are initiated apparently from within the enhancer and elongated through the intervening DNA into the cis-linked CAT gene. In nonerythroid HL-60 cells in which the HS2 enhancer is inactive, long enhancer transcripts are not detectable. Splitting the HS2 enhancer between two tandem Ap1 sites abolishes the synthesis of a group of long enhancer transcripts and results in loss of enhancer function and transcriptional silencing of the cis-linked CAT gene. In directing the synthesis of RNA through the intervening DNA and the gene by a tracking and transcription mechanism, the HS2 enhancer may (i) open up the chromatin structure of a gene domain and (ii) deliver enhancer binding proteins to the promoter sequence where they may stimulate the transcription of the gene at the cap site.\n"
],
"offsets": [
[
0,
1399
]
]
}
] | [
{
"id": "PMID-1454801_T1",
"type": "Protein",
"text": [
"beta-like globin"
],
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[
198,
214
]
],
"normalized": []
},
{
"id": "PMID-1454801_T2",
"type": "Protein",
"text": [
"chloramphenicol acetyltransferase"
],
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429,
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]
],
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},
{
"id": "PMID-1454801_T3",
"type": "Protein",
"text": [
"CAT"
],
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464,
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]
],
"normalized": []
},
{
"id": "PMID-1454801_T4",
"type": "Protein",
"text": [
"CAT"
],
"offsets": [
[
725,
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]
],
"normalized": []
},
{
"id": "PMID-1454801_T5",
"type": "Protein",
"text": [
"CAT"
],
"offsets": [
[
1057,
1060
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"id": "PMID-1454801_T6",
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"hypersensitive site HS2 enhancer"
],
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21,
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],
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"id": "PMID-1454801_T7",
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"human genome"
],
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82,
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"id": "PMID-1454801_T8",
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100,
151
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"id": "PMID-1454801_T9",
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],
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187,
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"id": "PMID-1454801_T10",
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516,
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"id": "PMID-1454801_T13",
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"text": [
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],
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544,
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"id": "PMID-1454801_T14",
"type": "Entity",
"text": [
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],
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654,
662
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},
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"id": "PMID-1454801_T15",
"type": "Entity",
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"intervening DNA"
],
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689,
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"id": "PMID-1454801_T16",
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"id": "PMID-1454801_T17",
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"id": "PMID-1454801_T18",
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],
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"id": "PMID-1454801_T19",
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"id": "PMID-1454801_T20",
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1189,
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},
{
"id": "PMID-1454801_T21",
"type": "Entity",
"text": [
"chromatin structure"
],
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1222,
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},
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"id": "PMID-1454801_T22",
"type": "Entity",
"text": [
"gene domain"
],
"offsets": [
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1247,
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"id": "PMID-1454801_T23",
"type": "Entity",
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1276,
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{
"id": "PMID-1454801_T24",
"type": "Entity",
"text": [
"cap site"
],
"offsets": [
[
1389,
1397
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"normalized": []
}
] | [] | [
{
"id": "PMID-1454801_1",
"entity_ids": [
"PMID-1454801_T2",
"PMID-1454801_T3"
]
}
] | [
{
"id": "PMID-1454801_R1",
"type": "Protein-Component",
"arg1_id": "PMID-1454801_T1",
"arg2_id": "PMID-1454801_T8",
"normalized": []
}
] |
163 | PMID-7590666 | [
{
"id": "PMID-7590666__text",
"type": "abstract",
"text": [
"Vitamin E therapy of acute CCl4-induced hepatic injury in mice is associated with inhibition of nuclear factor kappa B binding. \nOxidative stress, with reactive oxygen intermediate formation, may represent a common mechanism by which liver injury is induced by diverse etiologies. Oxidative stress enhances nuclear factor kappa B (NF-kappa B) activity, and NF-kappa B activity has been shown to enhance the expression of cytotoxic cytokines. Acute hepatic injury caused by reactive oxygen intermediate production was induced by an intraperitoneal injection of CCl4 in mice. This injury was significantly inhibited by intravenous pretreatment of the mice with a water-soluble emulsion of alpha-tocopherol. Alpha-tocopherol treatment of the mice given the CCl4 also reduced the NF-kappa B binding to levels approaching those found in normal mice. In vitro treatment of a monocyte/macrophage cell line with CCl4 led to enhanced NF-kappa B binding and an increase in tumor necrosis factor-alpha (TNF-alpha) messenger RNA levels. Liver specimens taken from patients with acute fulminant hepatitis had markedly increased NF-kappa B binding activity in comparison with the binding of normal livers. These data demonstrate that abolishing acute hepatic injury with alpha-tocopherol, a free radical scavenger, also eliminated increased NF-kappa B binding. It is tempting to speculate that enhanced NF-kappa B expression caused by free radical production/oxidative stress may modulate liver injury, perhaps through an effect on cytotoxic cytokine synthesis.\n"
],
"offsets": [
[
0,
1548
]
]
}
] | [
{
"id": "PMID-7590666_T1",
"type": "Protein",
"text": [
"tumor necrosis factor-alpha"
],
"offsets": [
[
963,
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]
],
"normalized": []
},
{
"id": "PMID-7590666_T2",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
992,
1001
]
],
"normalized": []
},
{
"id": "PMID-7590666_T3",
"type": "Entity",
"text": [
"nuclear factor kappa B"
],
"offsets": [
[
96,
118
]
],
"normalized": []
},
{
"id": "PMID-7590666_T4",
"type": "Entity",
"text": [
"nuclear factor kappa B"
],
"offsets": [
[
307,
329
]
],
"normalized": []
},
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"id": "PMID-7590666_T5",
"type": "Entity",
"text": [
"NF-kappa B"
],
"offsets": [
[
331,
341
]
],
"normalized": []
},
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"id": "PMID-7590666_T6",
"type": "Entity",
"text": [
"NF-kappa B"
],
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[
357,
367
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],
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},
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"id": "PMID-7590666_T7",
"type": "Entity",
"text": [
"NF-kappa B"
],
"offsets": [
[
776,
786
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},
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"id": "PMID-7590666_T8",
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"NF-kappa B"
],
"offsets": [
[
925,
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"id": "PMID-7590666_T9",
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"text": [
"NF-kappa B"
],
"offsets": [
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1389,
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}
] | [] | [
{
"id": "PMID-7590666_1",
"entity_ids": [
"PMID-7590666_T1",
"PMID-7590666_T2"
]
}
] | [] |
164 | PMID-9398163 | [
{
"id": "PMID-9398163__text",
"type": "abstract",
"text": [
"ATF1 and CREB trans-activate a cell cycle regulated histone H4 gene at a distal nuclear matrix associated promoter element. \nProteins of the ATF/CREB class of transcription factors stimulate gene expression of several cell growth-related genes through protein kinase A-related cAMP response elements. The promoter activity of cell cycle regulated histone H4 genes is regulated by at least four principal cis-acting elements which mediate G1/S phase control and/or enhancement of transcription during the cell cycle. Using protein-DNA interaction assays we show that the H4 promoter contains two ATF/CREB recognition motifs which interact with CREB, ATF1, and ATF2 but not with ATF4/CREB2. One ATF/CRE motif is located in the distal promoter at the nuclear matrix-associated Site IV, and the second motif is present in the proximal promoter at Site I. Both ATF/CRE motifs overlap binding sequences for the multifunctional YY1 transcription factor, which has previously been shown to be nuclear matrix associated. Subnuclear fractionation reveals that there are two ATF1 isoforms which appear to differ with respect to DNA binding activity and partition selectively between nuclear matrix and nonmatrix compartments, consistent with the role of the nuclear matrix in regulating gene expression. Site-directed mutational studies demonstrate that Site I and Site IV together support ATF1- and CREB-induced trans-activation of the H4 promoter. Thus, our data establish that ATF/CREB factors functionally modulate histone H4 gene transcription at distal and proximal promoter elements.\n"
],
"offsets": [
[
0,
1580
]
]
}
] | [
{
"id": "PMID-9398163_T1",
"type": "Protein",
"text": [
"ATF1"
],
"offsets": [
[
0,
4
]
],
"normalized": []
},
{
"id": "PMID-9398163_T2",
"type": "Protein",
"text": [
"histone H4"
],
"offsets": [
[
52,
62
]
],
"normalized": []
},
{
"id": "PMID-9398163_T3",
"type": "Protein",
"text": [
"histone H4"
],
"offsets": [
[
347,
357
]
],
"normalized": []
},
{
"id": "PMID-9398163_T4",
"type": "Protein",
"text": [
"ATF1"
],
"offsets": [
[
649,
653
]
],
"normalized": []
},
{
"id": "PMID-9398163_T5",
"type": "Protein",
"text": [
"ATF2"
],
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[
659,
663
]
],
"normalized": []
},
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"id": "PMID-9398163_T6",
"type": "Protein",
"text": [
"ATF4"
],
"offsets": [
[
677,
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]
],
"normalized": []
},
{
"id": "PMID-9398163_T7",
"type": "Protein",
"text": [
"CREB2"
],
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[
682,
687
]
],
"normalized": []
},
{
"id": "PMID-9398163_T8",
"type": "Protein",
"text": [
"ATF1"
],
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1064,
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},
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"id": "PMID-9398163_T9",
"type": "Protein",
"text": [
"ATF1"
],
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1379,
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"normalized": []
},
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"id": "PMID-9398163_T10",
"type": "Protein",
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"H4"
],
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1426,
1428
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},
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"id": "PMID-9398163_T11",
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],
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1508,
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},
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"id": "PMID-9398163_T12",
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"distal nuclear matrix associated promoter element"
],
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[
73,
122
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],
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},
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"id": "PMID-9398163_T13",
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"cell growth-related genes"
],
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218,
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],
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},
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"id": "PMID-9398163_T14",
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"protein kinase A-related cAMP response elements"
],
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252,
299
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],
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},
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"id": "PMID-9398163_T15",
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"principal cis-acting elements"
],
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394,
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"id": "PMID-9398163_T16",
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],
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570,
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"id": "PMID-9398163_T17",
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"text": [
"ATF/CREB recognition motifs"
],
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595,
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"id": "PMID-9398163_T18",
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],
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693,
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},
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"id": "PMID-9398163_T19",
"type": "Entity",
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"distal promoter"
],
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725,
740
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],
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},
{
"id": "PMID-9398163_T20",
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"nuclear matrix-associated Site IV"
],
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[
748,
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},
{
"id": "PMID-9398163_T21",
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"proximal promoter"
],
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822,
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},
{
"id": "PMID-9398163_T22",
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"Site I"
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843,
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"id": "PMID-9398163_T23",
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"ATF/CRE motifs"
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856,
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},
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"id": "PMID-9398163_T24",
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"binding sequences"
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},
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"id": "PMID-9398163_T25",
"type": "Entity",
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"DNA"
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1117,
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},
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"id": "PMID-9398163_T26",
"type": "Entity",
"text": [
"Site I"
],
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}
] |
165 | PMID-9109677 | [
{
"id": "PMID-9109677__text",
"type": "abstract",
"text": [
"Involvement of an SAF-like transcription factor in the activation of serum amyloid A gene in monocyte/macrophage cells by lipopolysaccharide. \nSerum amyloid A (SAA) has been linked to atherosclerosis because of its ability to remodel high-density lipoprotein by the depletion of apolipoprotein A1, its ability to bind cholesterol, and its presence in the atherosclerotic plaques of coronary and carotid arteries. In the present study, we investigated the induction mechanism of SAA gene in THP-1 monocyte/macrophage cells which play a critical role in the development of atherosclerotic fatty streak and plaque formation. We and others have shown that SAA gene is induced in monocyte/macrophage cells by lipopolysaccharide (LPS). By promoter function analysis, we show that the SAA promoter sequence between -280 and -226 can confer LPS responsiveness. Gel electrophoretic mobility shift assay detected an induced DNA-binding activity in these cells in response to LPS. Characterization of the DNA-binding protein by UV cross-linking, Southwestern blot, and antibody ablation/supershift assays revealed that it is similar to a recently reported nuclear factor designated SAF. These results demonstrated that LPS-mediated SAA gene induction in monocyte/macrophage cells is primarily due to the induction of SAF activity.\n"
],
"offsets": [
[
0,
1320
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]
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"id": "PMID-9109677_T1",
"type": "Protein",
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"serum amyloid A"
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"id": "PMID-9109677_T2",
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"id": "PMID-9109677_T3",
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"id": "PMID-9109677_T4",
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"id": "PMID-9109677_1",
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}
] |
166 | PMID-10069412 | [
{
"id": "PMID-10069412__text",
"type": "abstract",
"text": [
"Anti-rheumatic compound aurothioglucose inhibits tumor necrosis factor-alpha-induced HIV-1 replication in latently infected OM10.1 and Ach2 cells. \nNF-kappaB is a potent cellular activator of HIV-1 gene expression. Down-regulation of NF-kappaB activation is known to inhibit HIV replication from the latently infected cells. Gold compounds have been effectively used for many decades in the treatment of rheumatoid arthritis. We previously reported that gold compounds, especially aurothioglucose (AuTG) containing monovalent gold ion, inhibited the DNA-binding of NF-kappaB in vitro. In this report we have examined the efficacy of the gold compound AuTG as an inhibitor of HIV replication in latently infected OM10.1 and Ach2 cells. Tumor necrosis factor (TNF)-alpha-induced HIV-1 replication in OM10.1 or Ach2 cells was significantly inhibited by non-cytotoxic doses of AuTG (>10 microM in OM10.1 cells and >25 F.M in Ach2 cells), while 25 microM of the counter-anion thioglucose (TG) or gold compound containing divalent gold ion, HAuCl3, had no effect. The effect of AuTG on NF-kappaB-dependent gene expression was confirmed by a transient CAT assay. Specific staining as well as electron microscopic examinations revealed the accumulation of metal gold in the cells, supporting our previous hypothesis that gold ions could block NF-kappaB-DNA binding by a redox mechanism. These observations indicate that the monovalent gold compound AuTG is a potentially useful drug for the treatment of patients infected with HIV.\n"
],
"offsets": [
[
0,
1524
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]
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"id": "PMID-10069412_T1",
"type": "Protein",
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],
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"id": "PMID-10069412_T2",
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"id": "PMID-10069412_T3",
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"id": "PMID-10069412_T4",
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"id": "PMID-10069412_T5",
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] | [] | [] | [] |
167 | PMID-10372271 | [
{
"id": "PMID-10372271__text",
"type": "abstract",
"text": [
"Novel therapies for inflammatory bowel disease. \nLooking back at successes and failures in newer approaches to treating IBD, it is tempting--although still difficult--to draw conclusions about pathogenesis. When a therapy proves effective, do clinicians truly know how it works? Even with a therapy as specific as anti-TNF antibody, it is not clear if the benefit is attributable to simple binding and clearance of TNF-alpha or to binding on the cell surface and subsequent deletion of the activated macrophage. When a drug appears to be less effective than preclinical models suggest, can failures in effectiveness from delivery or dosing be differentiated? The disappointing results of clinical trials with IL-10--so at odds with the prediction of benefit from animal models--bring into question the validity of those models as well as the soundness of design of the clinical trials on which efficacy of IL-10 is judged. The variability of response even to the most narrowly targeted agents suggests that these diseases are far more heterogeneous in humans than in their murine counterparts. Clinicians are only just beginning to recognize subclinical markers of response, and it may soon be possible to predict response on the basis of genetic composition. For the moment, however, the field of pharmacogenetics is embryonic. Challenges in developing new therapeutic strategies include not only identifying novel agents, but also improving the definitions of clinical endpoints and defining efficacy at the biologic level. Only through considered evaluation of clinical evidence may clinicians determine which therapies should remain novelties and which should become an accepted part of the armamentarium.\n"
],
"offsets": [
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0,
1710
]
]
}
] | [
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"id": "PMID-10372271_T1",
"type": "Protein",
"text": [
"TNF-alpha"
],
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415,
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},
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"id": "PMID-10372271_T2",
"type": "Protein",
"text": [
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},
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"id": "PMID-10372271_T3",
"type": "Protein",
"text": [
"IL-10"
],
"offsets": [
[
906,
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]
],
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}
] | [] | [] | [] |
168 | PMID-8513868 | [
{
"id": "PMID-8513868__text",
"type": "abstract",
"text": [
"Dependence for the proliferative response to erythropoietin on an established erythroid differentiation program in a human hematopoietic cell line, UT-7. \nErythroid differentiation involves the activation of a number of erythroid-specific genes, most of which, including the globin genes and the erythropoietin receptor (Epo-R) gene, are, at least in part, regulated by the transcription factor GATA-1. In order to understand the relationship, if any, between expression of GATA-1, response to Epo and erythroid differentiation, we analyzed the expression of GATA-1, Epo-R and globin genes in an Epo-dependent human cell line, UT-7 Epo. The results were compared to those obtained with the parental granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent cell line, UT-7, which has a predominantly megakaryoblastic phenotype and is unable to proliferate continuously in the presence of Epo. UT-7 Epo and UT-7 expressed similar levels of GATA-1 mRNA and binding activity. The two lines also expressed comparable levels of Epo-R mRNA while the number of Epo-binding sites on UT-7 Epo cells was one-sixth the number of UT-7 cells (2400 +/- 3 vs. 13,800 +/- 300). This difference in the number of binding sites could be due to differences in cell surface (UT-7 cells are 20% smaller than the parental UT-7 cells) or in receptor turnover. By Northern analysis, UT-7 cells expressed detectable levels of beta- and gamma-globin but not alpha-globin. In comparison, UT-7 Epo cells expressed alpha-globin and higher levels of gamma-globin (5-fold) and beta-globin (from barely to clearly detectable). Globin chains (alpha, beta and gamma) were clearly detectable by affinity chromatography in UT-7 Epo but not in UT-7 cells. The frequency of the cells which expressed beta- and gamma- globin genes in the two cell populations was measured by immunofluorescence with beta- and gamma-specific antibodies. The number of gamma-positive cells and their fluorescence intensity were higher in UT-7 Epo than in UT-7 cells (0 to 17% barely positive cells and 23 to 40% clearly positive cells, respectively), indicating that the increase in globin mRNA observed in UT-7 Epo is due to both an increase of gene expression per cell and an increase in numbers of cells containing gamma-globin. The levels of GATA-1, Epo-R and globin mRNA expressed were not affected by a 24-hour incubation of either cell line with Epo, GM-CSF or interleukin-3 (IL-3). (ABSTRACT TRUNCATED AT 400 WORDS)\n"
],
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[
0,
2475
]
]
}
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"id": "PMID-8513868_T1",
"type": "Protein",
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"erythropoietin"
],
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45,
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"id": "PMID-8513868_T2",
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],
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"id": "PMID-8513868_T3",
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321,
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"id": "PMID-8513868_T4",
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474,
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"id": "PMID-8513868_T6",
"type": "Protein",
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"Epo"
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494,
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"id": "PMID-8513868_T7",
"type": "Protein",
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559,
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"id": "PMID-8513868_T8",
"type": "Protein",
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],
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567,
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},
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"id": "PMID-8513868_T9",
"type": "Protein",
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"Epo"
],
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596,
599
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],
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},
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"id": "PMID-8513868_T10",
"type": "Protein",
"text": [
"granulocyte-macrophage colony-stimulating factor"
],
"offsets": [
[
699,
747
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],
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},
{
"id": "PMID-8513868_T11",
"type": "Protein",
"text": [
"GM-CSF"
],
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749,
755
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},
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"id": "PMID-8513868_T12",
"type": "Protein",
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"Epo"
],
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898,
901
]
],
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},
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"id": "PMID-8513868_T13",
"type": "Protein",
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"GATA-1"
],
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949,
955
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],
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},
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"id": "PMID-8513868_T14",
"type": "Protein",
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"Epo-R"
],
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[
1033,
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},
{
"id": "PMID-8513868_T15",
"type": "Protein",
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"Epo"
],
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[
1064,
1067
]
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},
{
"id": "PMID-8513868_T16",
"type": "Protein",
"text": [
"alpha-globin"
],
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1441,
1453
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],
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},
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"id": "PMID-8513868_T17",
"type": "Protein",
"text": [
"alpha-globin"
],
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1495,
1507
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},
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"id": "PMID-8513868_T18",
"type": "Protein",
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"beta-globin"
],
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1555,
1566
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"id": "PMID-8513868_T19",
"type": "Protein",
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],
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1604,
1624
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},
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"id": "PMID-8513868_T20",
"type": "Protein",
"text": [
"beta"
],
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1626,
1630
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},
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"id": "PMID-8513868_T21",
"type": "Protein",
"text": [
"gamma"
],
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1635,
1640
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},
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"id": "PMID-8513868_T22",
"type": "Protein",
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],
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2297,
2303
]
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},
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"id": "PMID-8513868_T23",
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"Epo-R"
],
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2305,
2310
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},
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"id": "PMID-8513868_T24",
"type": "Protein",
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"Epo"
],
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2404,
2407
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},
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"id": "PMID-8513868_T25",
"type": "Protein",
"text": [
"GM-CSF"
],
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2409,
2415
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],
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},
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"id": "PMID-8513868_T26",
"type": "Protein",
"text": [
"interleukin-3"
],
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2419,
2432
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],
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},
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"id": "PMID-8513868_T27",
"type": "Protein",
"text": [
"IL-3"
],
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[
2434,
2438
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],
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},
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"id": "PMID-8513868_T28",
"type": "Entity",
"text": [
"erythroid-specific genes"
],
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[
220,
244
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],
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},
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"id": "PMID-8513868_T29",
"type": "Entity",
"text": [
"globin genes"
],
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[
275,
287
]
],
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},
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"id": "PMID-8513868_T30",
"type": "Entity",
"text": [
"globin genes"
],
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[
577,
589
]
],
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},
{
"id": "PMID-8513868_T31",
"type": "Entity",
"text": [
"beta-"
],
"offsets": [
[
1771,
1776
]
],
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},
{
"id": "PMID-8513868_T32",
"type": "Entity",
"text": [
"gamma- globin genes"
],
"offsets": [
[
1781,
1800
]
],
"normalized": []
}
] | [] | [
{
"id": "PMID-8513868_1",
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"PMID-8513868_T2",
"PMID-8513868_T3"
]
},
{
"id": "PMID-8513868_2",
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"PMID-8513868_T11"
]
},
{
"id": "PMID-8513868_3",
"entity_ids": [
"PMID-8513868_T26",
"PMID-8513868_T27"
]
}
] | [] |
169 | PMID-10455134 | [
{
"id": "PMID-10455134__text",
"type": "abstract",
"text": [
"AML1 (CBFalpha2) cooperates with B cell-specific activating protein (BSAP/PAX5) in activation of the B cell-specific BLK gene promoter. \nAML1 plays a critical role during hematopoiesis and chromosomal translocations involving AML1 are commonly associated with different forms of leukemia, including pre-B acute lymphoblastic leukemia. To understand the function of AML1 during B cell differentiation, we analyzed regulatory regions of B cell-specific genes for potential AML1-binding sites and have identified a putative AML1-binding site in the promoter of the B cell-specific tyrosine kinase gene, blk. Gel mobility shift assays and transient transfection assays demonstrate that AML1 binds specifically to this site in the blk promoter and this binding site is important for blk promoter activity. Furthermore, in vitro binding analysis revealed that the AML1 runt DNA-binding domain physically interacts with the paired DNA-binding domain of BSAP, a B cell-specific transcription factor. BSAP has been shown previously to be important for B cell-specific regulation of the blk gene. Physical interaction of AML1 with BSAP correlates with functional cooperativity in transfection studies where AML1 and BSAP synergistically activate blk promoter transcription by more than 50-fold. These results demonstrate physical and functional interactions between AML1 and BSAP and suggest that AML1 is an important factor for regulating a critical B cell-specific gene, blk.\n"
],
"offsets": [
[
0,
1468
]
]
}
] | [
{
"id": "PMID-10455134_T1",
"type": "Protein",
"text": [
"AML1"
],
"offsets": [
[
0,
4
]
],
"normalized": []
},
{
"id": "PMID-10455134_T2",
"type": "Protein",
"text": [
"CBFalpha2"
],
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[
6,
15
]
],
"normalized": []
},
{
"id": "PMID-10455134_T3",
"type": "Protein",
"text": [
"B cell-specific activating protein"
],
"offsets": [
[
33,
67
]
],
"normalized": []
},
{
"id": "PMID-10455134_T4",
"type": "Protein",
"text": [
"BSAP"
],
"offsets": [
[
69,
73
]
],
"normalized": []
},
{
"id": "PMID-10455134_T5",
"type": "Protein",
"text": [
"PAX5"
],
"offsets": [
[
74,
78
]
],
"normalized": []
},
{
"id": "PMID-10455134_T6",
"type": "Protein",
"text": [
"BLK"
],
"offsets": [
[
117,
120
]
],
"normalized": []
},
{
"id": "PMID-10455134_T7",
"type": "Protein",
"text": [
"AML1"
],
"offsets": [
[
137,
141
]
],
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},
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"id": "PMID-10455134_T8",
"type": "Protein",
"text": [
"AML1"
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"offsets": [
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226,
230
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170 | PMID-7739562 | [
{
"id": "PMID-7739562__text",
"type": "abstract",
"text": [
"Coupling of a signal response domain in I kappa B alpha to multiple pathways for NF-kappa B activation. \nThe eukaryotic transcription factor NF-kappa B plays a central role in the induced expression of human immunodeficiency virus type 1 and in many aspects of the genetic program mediating normal T-cell activation and growth. The nuclear activity of NF-kappa B is tightly regulated from the cytoplasmic compartment by an inhibitory subunit called I kappa B alpha. This cytoplasmic inhibitor is rapidly phosphorylated and degraded in response to a diverse set of NF-kappa B-inducing agents, including T-cell mitogens, proinflammatory cytokines, and viral transactivators such as the Tax protein of human T-cell leukemia virus type 1. To explore these I kappa B alpha-dependent mechanisms for NF-kappa B induction, we identified novel mutants of I kappa B alpha that uncouple its inhibitory and signal-transducing functions in human T lymphocytes. Specifically, removal of the N-terminal 36 amino acids of I kappa B alpha failed to disrupt its ability to form latent complexes with NF-kappa B in the cytoplasm. However, this deletion mutation prevented the induced phosphorylation, degradative loss, and functional release of I kappa B alpha from NF-kappa B in Tax-expressing cells. Alanine substitutions introduced at two serine residues positioned within this N-terminal regulatory region of I kappa B alpha also yielded constitutive repressors that escaped from Tax-induced turnover and that potently inhibited immune activation pathways for NF-kappa B induction, including those initiated from antigen and cytokine receptors. In contrast, introduction of a phosphoserine mimetic at these sites rectified this functional defect, a finding consistent with a causal linkage between the phosphorylation status and proteolytic stability of this cytoplasmic inhibitor. Together, these in vivo studies define a critical signal response domain in I kappa B alpha that coordinately controls the biologic activities of I kappa B alpha and NF-kappa B in response to viral and immune stimuli.\n"
],
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0,
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"id": "PMID-7739562_T1",
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"I kappa B alpha"
],
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"id": "PMID-7739562_T2",
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"I kappa B alpha"
],
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"id": "PMID-7739562_T3",
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],
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"id": "PMID-7739562_T4",
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"id": "PMID-7739562_T5",
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"id": "PMID-7739562_T8",
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"id": "PMID-7739562_T9",
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"id": "PMID-7739562_T11",
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"id": "PMID-7739562_T12",
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"id": "PMID-7739562_T13",
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"signal response domain"
],
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"id": "PMID-7739562_T14",
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"id": "PMID-7739562_T22",
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],
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},
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"id": "PMID-7739562_T27",
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],
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},
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"text": [
"NF-kappa B"
],
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}
] | [] | [] | [
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}
] |
171 | PMID-7692906 | [
{
"id": "PMID-7692906__text",
"type": "abstract",
"text": [
"Inhibition of HIV-1 latency reactivation by dehydroepiandrosterone (DHEA) and an analog of DHEA. \nThe initial infection with human immunodeficiency virus type 1 (HIV-1) in most individuals usually results in the establishment of a latent or chronic infection before eventual progression toward acquired immunodeficiency syndrome. HIV-1 can also establish a latent or persistent infection in some T cell lines that show minimal constitutive virus expression. However, activation of the T cell lines leading to enhanced HIV-1 replication can be induced by antigens, mitogens, and cytokines (tumor necrosis factor alpha [TNF-alpha], interleukin 1, and interleukin-2). Various gene products from other viruses (HTLV-1, HSV, EBV, CMV, HBV, and HHV-6) can also enhance HIV-1 long terminal repeat (LTR)-driven reporter gene activity. On the basis of these observations, it has been proposed that reactivation of latent HIV-1 harbored in chronically infected T lymphocytes, monocytes, or macrophages plays an important role in the pathogenesis of AIDS. So far, there are no drugs or therapy available that can provide protection against HIV-1 latency reactivation. ACH-2, derived from a human T cell line (CEM), is chronically infected with HIV-1, with low levels of constitutive virus expression. ACH-2 can be converted to productive infection by stimulation of the cells with 12-O-tetradecanoylphorbol-13-acetate (TPA), mitogen or cytokines (TNF-alpha), or infection with HSV. Therefore the ACH-2 cell line is a good candidate for studying the effects of drugs on HIV-1 activation. Previously, we have reported that DHEA and synthetic analogs of DHEA can be modest inhibitors of HIV-1 IIIB replication in phytohemagglutinin-stimulated peripheral blood lymphocyte cultures. (ABSTRACT TRUNCATED AT 250 WORDS)\n"
],
"offsets": [
[
0,
1801
]
]
}
] | [
{
"id": "PMID-7692906_T1",
"type": "Protein",
"text": [
"tumor necrosis factor alpha"
],
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[
589,
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]
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"normalized": []
},
{
"id": "PMID-7692906_T2",
"type": "Protein",
"text": [
"TNF-alpha"
],
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618,
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]
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},
{
"id": "PMID-7692906_T3",
"type": "Protein",
"text": [
"interleukin-2"
],
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[
649,
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},
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"id": "PMID-7692906_T4",
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"text": [
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1436,
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"id": "PMID-7692906_T5",
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"phytohemagglutinin"
],
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1699,
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]
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},
{
"id": "PMID-7692906_T6",
"type": "Entity",
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"HIV-1 long terminal repeat (LTR)"
],
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[
763,
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},
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"id": "PMID-7692906_T7",
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791,
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"id": "PMID-7692906_T8",
"type": "Entity",
"text": [
"reporter gene"
],
"offsets": [
[
803,
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"normalized": []
}
] | [] | [] | [] |
172 | PMID-1896645 | [
{
"id": "PMID-1896645__text",
"type": "abstract",
"text": [
"Induction of NF-kappa B during monocyte differentiation is associated with activation of HIV-gene expression. \nCells of the monocyte-macrophage lineage are important targets of HIV infection. We report here that the phenotypic differentiation of monocyte cell lines induced by phorbol esters or tumour necrosis factor alpha (TNF alpha) is associated with expression of nuclear factor kappa B (NF-kappa B). In parallel with such differentiation, HIV transcription, monitored using an HIV long terminal repeat reporter gene construct, is activated in such cells under the influence of enhanced NF-kappa B expression. Also, in a promonocyte cell line chronically infected with HIV, NF-kappa B expression and HIV transcription were enhanced on stimulation with phorbol ester or TNF alpha. Thus, stimulation of monocyte cell lines by phorbol esters or TNF alpha induces cell differentiation and activates HIV transcription. Such a process may have fundamental implications in AIDS pathogenesis in vivo and may be important in disease progression induced by opportunistic infections directly or indirectly involving macrophages.\n"
],
"offsets": [
[
0,
1123
]
]
}
] | [
{
"id": "PMID-1896645_T1",
"type": "Protein",
"text": [
"tumour necrosis factor alpha"
],
"offsets": [
[
295,
323
]
],
"normalized": []
},
{
"id": "PMID-1896645_T2",
"type": "Protein",
"text": [
"TNF alpha"
],
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[
325,
334
]
],
"normalized": []
},
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"id": "PMID-1896645_T3",
"type": "Protein",
"text": [
"TNF alpha"
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"id": "PMID-1896645_1",
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]
}
] | [] |
173 | PMID-10217534 | [
{
"id": "PMID-10217534__text",
"type": "abstract",
"text": [
"Cellular disposition of sulphamethoxazole and its metabolites: implications for hypersensitivity. \n1. Bioactivation of sulphamethoxazole (SMX) to chemically-reactive metabolites and subsequent protein conjugation is thought to be involved in SMX hypersensitivity. We have therefore examined the cellular metabolism, disposition and conjugation of SMX and its metabolites in vitro. 2. Flow cytometry revealed binding of N-hydroxy (SMX-NHOH) and nitroso (SMX-NO) metabolites of SMX, but not of SMX itself, to the surface of viable white blood cells. Cellular haptenation by SMX-NO was reduced by exogenous glutathione (GSH). 3. SMX-NHOH and SMX-NO were rapidly reduced back to the parent compound by cysteine (CYS), GSH, human peripheral blood cells and plasma, suggesting that this is an important and ubiquitous bioinactivation mechanism. 4. Fluorescence HPLC showed that SMX-NHOH and SMX-NO depleted CYS and GSH in buffer, and to a lesser extent, in cells and plasma. 5. Neutrophil apoptosis and inhibition of neutrophil function were induced at lower concentrations of SMX-NHOH and SMX-NO than those inducing loss of membrane viability, with SMX having no effect. Lymphocytes were significantly (P<0.05) more sensitive to the direct cytotoxic effects of SMX-NO than neutrophils. 6. Partitioning of SMX-NHOH into red blood cells was significantly (P<0.05) lower than with the hydroxylamine of dapsone. 7. Our results suggest that the balance between oxidation of SMX to its toxic metabolites and their reduction is an important protective cellular mechanism. If an imbalance exists, haptenation of the toxic metabolites to bodily proteins including the surface of viable cells can occur, and may result in drug hypersensitivity.\n"
],
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0,
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"id": "PMID-10217534_T3",
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] | [] | [] | [] |
174 | PMID-8662845 | [
{
"id": "PMID-8662845__text",
"type": "abstract",
"text": [
"Cooperation between core binding factor and adjacent promoter elements contributes to the tissue-specific expression of interleukin-3. \nTissue-specific expression of interleukin-3 (IL-3) is mediated via cis-acting elements located within 315 base pairs of the transcription start. This is achieved in part through the positive activities of the AP-1 and Elf-1 sites in the IL-3 promoter. The contribution to T cell-specific expression by other promoter sites was assessed in a transient expression assay with IL-3 promoter constructs linked to a luciferase gene, focusing initially on the core binding factor (CBF) site, which is footprinted in vivo upon T cell activation. Activity of the CBF site is shown to be critically dependent on the adjacent activator site Act-1. Together the Act-1 and CBF sites form a functional unit (AC unit) with dual activity. The AC unit is demonstrated to enhance basal activity of promoters both in fibroblasts and T cells. This activity is further inducible in activated T cells, but not in fibroblasts. In addition to the already identified NIP repressor site, evidence is presented for a second repressor region that restricts promoter activity in fibroblasts. Finally, a novel positive regulatory element has been mapped in the IL-3 promoter between nucleotide -180 and -210 that leads to increased expression in T cells. Together these results demonstrate that T cell expression of IL-3 is not specified by the activity of a single tissue-specific element, but instead involves multiple interacting elements that provide both specific positive regulation in T cells and specific negative regulation in fibroblasts.\n"
],
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0,
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"id": "PMID-8662845_T1",
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"id": "PMID-8662845_T4",
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"id": "PMID-8662845_T10",
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"id": "PMID-8662845_T14",
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"promoter sites"
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444,
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"id": "PMID-8662845_T15",
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"luciferase gene"
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"id": "PMID-8662845_T16",
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"id": "PMID-8662845_T19",
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"id": "PMID-8662845_T20",
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"id": "PMID-8662845_T21",
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"adjacent activator site Act-1"
],
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"id": "PMID-8662845_T22",
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"id": "PMID-8662845_T23",
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"CBF sites"
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"id": "PMID-8662845_T24",
"type": "Entity",
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"functional unit"
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"id": "PMID-8662845_T25",
"type": "Entity",
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"id": "PMID-8662845_T27",
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"id": "PMID-8662845_T28",
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],
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"id": "PMID-8662845_T29",
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"second repressor region"
],
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"id": "PMID-8662845_T31",
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"positive regulatory element"
],
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"id": "PMID-8662845_T32",
"type": "Entity",
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"promoter"
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},
{
"id": "PMID-8662845_T33",
"type": "Entity",
"text": [
"tissue-specific element"
],
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"normalized": []
},
{
"id": "PMID-8662845_T34",
"type": "Entity",
"text": [
"interacting elements"
],
"offsets": [
[
1527,
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],
"normalized": []
}
] | [] | [
{
"id": "PMID-8662845_1",
"entity_ids": [
"PMID-8662845_T2",
"PMID-8662845_T3"
]
}
] | [
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},
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},
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"type": "Protein-Component",
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},
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},
{
"id": "PMID-8662845_R9",
"type": "Protein-Component",
"arg1_id": "PMID-8662845_T7",
"arg2_id": "PMID-8662845_T34",
"normalized": []
}
] |
175 | PMID-9548490 | [
{
"id": "PMID-9548490__text",
"type": "abstract",
"text": [
"Differential induction of DNA-binding activities following CD19 cross-linking in human B lineage cells. \nThe B cell-specific cell surface molecule CD19 is expressed at all stages of B cell development, including normal plasma cells, and mediates signal transduction via interaction with cytoplasmic effector proteins. Cross-linking CD19 on early human B lineage cells induces the formation of a CD19/Vav/phosphatidylinositol-3 kinase complex, tyrosine phosphorylation of CD19 and Vav, and activation of the Ras pathway. To further explore the ramifications of CD19 signaling, the current study examined whether phosphorylation of Elk-1, activation of activator protein-1 (AP-1), or activation of nuclear factor-kappaB (NF-kappaB) transcription factors occurred following CD19 cross-linking. The cells used were the BLIN-1 pre-B cell line expressing low levels of cell surface mu heavy chain associated with surrogate light chain and the 1E8 immature B cell line expressing cell surface mu/kappa. Lysates from CD19 cross-linked 1E8 cells induced robust phosphorylation of an Elk-1 fusion protein in vitro, whereas no phosphorylation of Elk-1 fusion protein occurred using lysates from CD19 cross-linked BLIN-1 cells. An electrophoretic mobility shift assay employing AP-1 and NF-kappaB consensus oligonucleotides was used to demonstrate that AP-1 -binding activity increased, while constitutive NF-kappaB-binding activity was not enhanced, following 2 h of CD19 cross-linking in 1E8 cells. Supershift experiments revealed that JunD and c-Fos proteins mediated anti-CD19 induced AP-1-binding activity in 1E8 cells. In contrast, CD19 cross-linking in BLIN-1 cells resulted in the induction of NF-kappaB, but had no apparent effect on AP-1-binding activity. These data suggest that CD19-mediated signal transduction activates different transcription factors at juxtaposed stages of B cell development that may culminate in the activation or suppression of distinct sets of genes.\n"
],
"offsets": [
[
0,
1976
]
]
}
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{
"id": "PMID-9548490_T1",
"type": "Protein",
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"CD19"
],
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59,
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"id": "PMID-9548490_T2",
"type": "Protein",
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147,
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]
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"id": "PMID-9548490_T3",
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332,
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"id": "PMID-9548490_T4",
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"id": "PMID-9548490_T5",
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},
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"id": "PMID-9548490_T33",
"type": "Entity",
"text": [
"AP-1"
],
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[
1731,
1735
]
],
"normalized": []
},
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"id": "PMID-9548490_T34",
"type": "Entity",
"text": [
"genes"
],
"offsets": [
[
1969,
1974
]
],
"normalized": []
}
] | [] | [] | [
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"id": "PMID-9548490_R1",
"type": "Protein-Component",
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"arg2_id": "PMID-9548490_T20",
"normalized": []
},
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"id": "PMID-9548490_R2",
"type": "Subunit-Complex",
"arg1_id": "PMID-9548490_T4",
"arg2_id": "PMID-9548490_T19",
"normalized": []
}
] |
176 | PMID-7964616 | [
{
"id": "PMID-7964616__text",
"type": "abstract",
"text": [
"DNA-binding studies of the Epstein-Barr virus nuclear antigen 2 (EBNA-2): evidence for complex formation by latent membrane protein gene promoter-binding proteins in EBNA-2-positive cell lines. \nThe Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA-2) protein is essential for the immortalization of human primary B cells by EBV. EBNA-2 trans-activates cellular and viral genes like CD23, c-fgr, latent membrane protein 1 (LMP1) and terminal protein 1 (TP1). Trans-activation of the TP1 promoter and of the BamHI C promoter has already been investigated in detail and appears to be mediated via protein-protein interactions and not by direct binding of EBNA-2 type A (of EBV type 1) to the DNA. EBNA-2 is able to trans-activate the expression of the LMP gene in several cell lines. Various reports have delineated the cis-acting elements of the LMP promoter through which EBNA-2 mediates trans-activation. To determine whether EBNA-2 also trans-activates the LMP promoter by protein-protein interactions, we performed a series of gel retardation assays and competition experiments with LMP promoter fragments of different sizes. We determined that the protein-binding region on the LMP promoter was within a 42 bp fragment encompassing nucleotides -135 to -176 relative to the LMP transcriptional start site. None of the DNA fragments investigated indicated interaction of EBNA-2 with the DNA via protein-protein interactions. No significant differences between EBNA-2-positive and EBNA-2-negative nuclear extracts could be seen in the gel retardation assay under conditions that clearly showed binding of EBNA-2A to the TP1 promoter. However, analysis of sucrose gradient fractions in the gel retardation assay provided evidence that the LMP promoter-binding proteins form a complex of higher M(r) in EBNA-2-positive cell extracts. These complexes were destroyed by detergent. We deduce from these results that EBNA-2-positive cells might indeed contain specific complexes bound to the LMP promoter which are, however, too labile to be detected in a standard gel retardation assay.\n"
],
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[
0,
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],
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"id": "PMID-7964616_T2",
"type": "Protein",
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"EBNA-2"
],
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65,
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"id": "PMID-7964616_T3",
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241
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"id": "PMID-7964616_T5",
"type": "Protein",
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243,
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"id": "PMID-7964616_T6",
"type": "Protein",
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"EBNA-2"
],
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329,
335
]
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},
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"id": "PMID-7964616_T7",
"type": "Protein",
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"CD23"
],
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382,
386
]
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"id": "PMID-7964616_T8",
"type": "Protein",
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"id": "PMID-7964616_T9",
"type": "Protein",
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"latent membrane protein 1"
],
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]
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"id": "PMID-7964616_T10",
"type": "Protein",
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"LMP1"
],
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]
],
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},
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"id": "PMID-7964616_T11",
"type": "Protein",
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"terminal protein 1"
],
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[
432,
450
]
],
"normalized": []
},
{
"id": "PMID-7964616_T12",
"type": "Protein",
"text": [
"TP1"
],
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[
452,
455
]
],
"normalized": []
},
{
"id": "PMID-7964616_T13",
"type": "Protein",
"text": [
"TP1"
],
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[
482,
485
]
],
"normalized": []
},
{
"id": "PMID-7964616_T14",
"type": "Protein",
"text": [
"BamHI C"
],
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[
506,
513
]
],
"normalized": []
},
{
"id": "PMID-7964616_T15",
"type": "Protein",
"text": [
"EBNA-2"
],
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[
652,
658
]
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},
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"id": "PMID-7964616_T16",
"type": "Protein",
"text": [
"EBNA-2"
],
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[
694,
700
]
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"normalized": []
},
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"id": "PMID-7964616_T17",
"type": "Protein",
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"LMP"
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752
]
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},
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"id": "PMID-7964616_T18",
"type": "Protein",
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"LMP"
],
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[
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]
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},
{
"id": "PMID-7964616_T19",
"type": "Protein",
"text": [
"EBNA-2"
],
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[
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877
]
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"normalized": []
},
{
"id": "PMID-7964616_T20",
"type": "Protein",
"text": [
"EBNA-2"
],
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[
926,
932
]
],
"normalized": []
},
{
"id": "PMID-7964616_T21",
"type": "Protein",
"text": [
"LMP"
],
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[
958,
961
]
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"normalized": []
},
{
"id": "PMID-7964616_T22",
"type": "Protein",
"text": [
"LMP"
],
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[
1085,
1088
]
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"normalized": []
},
{
"id": "PMID-7964616_T23",
"type": "Protein",
"text": [
"LMP"
],
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[
1181,
1184
]
],
"normalized": []
},
{
"id": "PMID-7964616_T24",
"type": "Protein",
"text": [
"EBNA-2"
],
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[
1372,
1378
]
],
"normalized": []
},
{
"id": "PMID-7964616_T25",
"type": "Protein",
"text": [
"EBNA-2"
],
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[
1461,
1467
]
],
"normalized": []
},
{
"id": "PMID-7964616_T26",
"type": "Protein",
"text": [
"EBNA-2"
],
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[
1481,
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]
],
"normalized": []
},
{
"id": "PMID-7964616_T27",
"type": "Protein",
"text": [
"EBNA-2A"
],
"offsets": [
[
1605,
1612
]
],
"normalized": []
},
{
"id": "PMID-7964616_T28",
"type": "Protein",
"text": [
"TP1"
],
"offsets": [
[
1620,
1623
]
],
"normalized": []
},
{
"id": "PMID-7964616_T29",
"type": "Protein",
"text": [
"LMP"
],
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[
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"normalized": []
},
{
"id": "PMID-7964616_T30",
"type": "Protein",
"text": [
"EBNA-2"
],
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[
1801,
1807
]
],
"normalized": []
},
{
"id": "PMID-7964616_T31",
"type": "Protein",
"text": [
"EBNA-2"
],
"offsets": [
[
1911,
1917
]
],
"normalized": []
},
{
"id": "PMID-7964616_T32",
"type": "Protein",
"text": [
"LMP"
],
"offsets": [
[
1986,
1989
]
],
"normalized": []
},
{
"id": "PMID-7964616_T33",
"type": "Entity",
"text": [
"DNA"
],
"offsets": [
[
0,
3
]
],
"normalized": []
},
{
"id": "PMID-7964616_T34",
"type": "Entity",
"text": [
"genes"
],
"offsets": [
[
371,
376
]
],
"normalized": []
},
{
"id": "PMID-7964616_T35",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
486,
494
]
],
"normalized": []
},
{
"id": "PMID-7964616_T36",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
514,
522
]
],
"normalized": []
},
{
"id": "PMID-7964616_T37",
"type": "Entity",
"text": [
"DNA"
],
"offsets": [
[
689,
692
]
],
"normalized": []
},
{
"id": "PMID-7964616_T38",
"type": "Entity",
"text": [
"cis-acting elements"
],
"offsets": [
[
817,
836
]
],
"normalized": []
},
{
"id": "PMID-7964616_T39",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
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"normalized": []
},
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"id": "PMID-7964616_T40",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
962,
970
]
],
"normalized": []
},
{
"id": "PMID-7964616_T41",
"type": "Entity",
"text": [
"protein-binding region"
],
"offsets": [
[
1151,
1173
]
],
"normalized": []
},
{
"id": "PMID-7964616_T42",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
1185,
1193
]
],
"normalized": []
},
{
"id": "PMID-7964616_T43",
"type": "Entity",
"text": [
"42 bp fragment"
],
"offsets": [
[
1207,
1221
]
],
"normalized": []
},
{
"id": "PMID-7964616_T44",
"type": "Entity",
"text": [
"nucleotides -135 to -176"
],
"offsets": [
[
1235,
1259
]
],
"normalized": []
},
{
"id": "PMID-7964616_T45",
"type": "Entity",
"text": [
"LMP transcriptional start site"
],
"offsets": [
[
1276,
1306
]
],
"normalized": []
},
{
"id": "PMID-7964616_T46",
"type": "Entity",
"text": [
"DNA fragments"
],
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[
1320,
1333
]
],
"normalized": []
},
{
"id": "PMID-7964616_T47",
"type": "Entity",
"text": [
"DNA"
],
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[
1388,
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],
"normalized": []
},
{
"id": "PMID-7964616_T48",
"type": "Entity",
"text": [
"promoter"
],
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[
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]
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"normalized": []
},
{
"id": "PMID-7964616_T49",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
1742,
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]
],
"normalized": []
},
{
"id": "PMID-7964616_T50",
"type": "Entity",
"text": [
"specific complexes"
],
"offsets": [
[
1954,
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]
],
"normalized": []
},
{
"id": "PMID-7964616_T51",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
1990,
1998
]
],
"normalized": []
}
] | [] | [
{
"id": "PMID-7964616_1",
"entity_ids": [
"PMID-7964616_T1",
"PMID-7964616_T2"
]
},
{
"id": "PMID-7964616_2",
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"PMID-7964616_T4",
"PMID-7964616_T5"
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},
{
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"entity_ids": [
"PMID-7964616_T9",
"PMID-7964616_T10"
]
},
{
"id": "PMID-7964616_4",
"entity_ids": [
"PMID-7964616_T11",
"PMID-7964616_T12"
]
}
] | [
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"type": "Protein-Component",
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"arg2_id": "PMID-7964616_T35",
"normalized": []
},
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"id": "PMID-7964616_R2",
"type": "Protein-Component",
"arg1_id": "PMID-7964616_T14",
"arg2_id": "PMID-7964616_T36",
"normalized": []
},
{
"id": "PMID-7964616_R3",
"type": "Protein-Component",
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"type": "Protein-Component",
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},
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},
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"type": "Protein-Component",
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"normalized": []
},
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"type": "Protein-Component",
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"arg2_id": "PMID-7964616_T42",
"normalized": []
},
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"type": "Protein-Component",
"arg1_id": "PMID-7964616_T28",
"arg2_id": "PMID-7964616_T48",
"normalized": []
},
{
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"type": "Protein-Component",
"arg1_id": "PMID-7964616_T29",
"arg2_id": "PMID-7964616_T49",
"normalized": []
},
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"type": "Protein-Component",
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"arg2_id": "PMID-7964616_T51",
"normalized": []
}
] |
177 | PMID-9756417 | [
{
"id": "PMID-9756417__text",
"type": "abstract",
"text": [
"Transcription factor activation in lymphokine activated killer cells and lymphocytes from patients receiving IL-2 immunotherapy. \nAdministration of the cytokine interleukin-2 (IL-2) can result in therapeutic benefits for individuals with renal cell carcinoma and melanoma. Here we report an analysis of the transcription factor families AP-1, Sp1, NF-kappaB, and signal transducers and activators of transcription (STAT) in cancer patients' lymphocytes before and after IL-2 immunotherapy, as assessed by a gel-shift assay. An in vitro surrogate of IL-2 immunotherapy is the incubation of fresh peripheral blood mononuclear cells (PBMC) from healthy individuals in IL-2 for several days, resulting in the production of lymphokine-activated killer (LAK) activity in these cultures. One purpose of this study was to describe the profile of transcription factor activation in these different populations, and assess whether the patterns observed correlated with functional differences in these cells. Prior to in vivo IL-2 administration, the typical binding pattern of transcription factors in PBMC from patients resembled that seen in fresh PBMC from healthy individuals. Over a 3-week course of IL-2 therapy, in most patients the binding patterns of AP-1 , Sp1, and NF-kappaB proteins changed to resemble those seen in PBMC activated by IL-2 in vitro. However, the cells obtained from IL-2-treated patients did not have low-level constitutive expression of STAT binding factors as did LAK cells. When these patient cells were further stimulated by IL-2 in vitro, additional differences in STAT induction patterns were noted. These data provide further information on the molecular events occurring in immune cells generated through in vivo and in vitro administration of IL-2, and further document that there is not a precise congruence between PBMC activated in vivo and in vitro by IL-2.\n"
],
"offsets": [
[
0,
1890
]
]
}
] | [
{
"id": "PMID-9756417_T1",
"type": "Protein",
"text": [
"IL-2"
],
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[
109,
113
]
],
"normalized": []
},
{
"id": "PMID-9756417_T2",
"type": "Protein",
"text": [
"interleukin-2"
],
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[
161,
174
]
],
"normalized": []
},
{
"id": "PMID-9756417_T3",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
176,
180
]
],
"normalized": []
},
{
"id": "PMID-9756417_T4",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
343,
346
]
],
"normalized": []
},
{
"id": "PMID-9756417_T5",
"type": "Protein",
"text": [
"IL-2"
],
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[
470,
474
]
],
"normalized": []
},
{
"id": "PMID-9756417_T6",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
549,
553
]
],
"normalized": []
},
{
"id": "PMID-9756417_T7",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
665,
669
]
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"normalized": []
},
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"id": "PMID-9756417_T8",
"type": "Protein",
"text": [
"IL-2"
],
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[
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},
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"id": "PMID-9756417_T9",
"type": "Protein",
"text": [
"IL-2"
],
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[
1195,
1199
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],
"normalized": []
},
{
"id": "PMID-9756417_T10",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
1257,
1260
]
],
"normalized": []
},
{
"id": "PMID-9756417_T11",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1337,
1341
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],
"normalized": []
},
{
"id": "PMID-9756417_T12",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1385,
1389
]
],
"normalized": []
},
{
"id": "PMID-9756417_T13",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1548,
1552
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],
"normalized": []
},
{
"id": "PMID-9756417_T14",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1771,
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],
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},
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"id": "PMID-9756417_T15",
"type": "Protein",
"text": [
"IL-2"
],
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[
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],
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},
{
"id": "PMID-9756417_T16",
"type": "Entity",
"text": [
"AP-1"
],
"offsets": [
[
337,
341
]
],
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},
{
"id": "PMID-9756417_T17",
"type": "Entity",
"text": [
"NF-kappaB"
],
"offsets": [
[
348,
357
]
],
"normalized": []
}
] | [] | [
{
"id": "PMID-9756417_1",
"entity_ids": [
"PMID-9756417_T2",
"PMID-9756417_T3"
]
}
] | [] |
178 | PMID-9710600 | [
{
"id": "PMID-9710600__text",
"type": "abstract",
"text": [
"Human T-cell leukemia virus type 1 Tax induction of NF-kappaB involves activation of the IkappaB kinase alpha (IKKalpha) and IKKbeta cellular kinases. \nTax corresponds to a 40-kDa transforming protein from the pathogenic retrovirus human T-cell leukemia virus type 1 (HTLV-1) that activates nuclear expression of the NF-kappaB/Rel family of transcription factors by an unknown mechanism. Tax expression promotes N-terminal phosphorylation and degradation of IkappaB alpha, a principal cytoplasmic inhibitor of NF-kappaB. Our studies now demonstrate that HTLV-1 Tax activates the recently identified cellular kinases IkappaB kinase alpha (IKKalpha) and IKKbeta, which normally phosphorylate IkappaB alpha on both of its N-terminal regulatory serines in response to tumor necrosis factor alpha (TNF-alpha) and interleukin-1 (IL-1) stimulation. In contrast, a mutant of Tax termed M22, which does not induce NF-kappaB, fails to activate either IKKalpha or IKKbeta. Furthermore, endogenous IKK enzymatic activity was significantly elevated in HTLV-1-infected and Tax-expressing T-cell lines. Transfection of kinase-deficient mutants of IKKalpha and IKKbeta into either human Jurkat T or 293 cells also inhibits NF-kappaB-dependent reporter gene expression induced by Tax. Similarly, a kinase-deficient mutant of NIK (NF-kappaB-inducing kinase), which represents an upstream kinase in the TNF-alpha and IL-1 signaling pathways leading to IKKalpha and IKKbeta activation, blocks Tax induction of NF-kappaB. However, plasma membrane-proximal elements in these proinflammatory cytokine pathways are apparently not involved since dominant negative mutants of the TRAF2 and TRAF6 adaptors, which effectively block signaling through the cytoplasmic tails of the TNF-alpha and IL-1 receptors, respectively, do not inhibit Tax induction of NF-kappaB. Together, these studies demonstrate that HTLV-1 Tax exploits a distal part of the proinflammatory cytokine signaling cascade leading to induction of NF-kappaB. The pathological alteration of this cytokine pathway leading to NF-kappaB activation by Tax may play a central role in HTLV-1-mediated transformation of human T cells, clinically manifested as the adult T-cell leukemia.\n"
],
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0,
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"id": "PMID-9710600_T13",
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"id": "PMID-9710600_T14",
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793,
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1308,
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1313,
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"id": "PMID-9710600_T24",
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1384,
1393
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1433,
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],
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},
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"id": "PMID-9710600_T26",
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],
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"id": "PMID-9710600_T29",
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"id": "PMID-9710600_T31",
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"id": "PMID-9710600_T32",
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"id": "PMID-9710600_T33",
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],
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52,
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"id": "PMID-9710600_T34",
"type": "Entity",
"text": [
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],
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317,
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},
{
"id": "PMID-9710600_T35",
"type": "Entity",
"text": [
"N-terminal"
],
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412,
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],
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},
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"id": "PMID-9710600_T36",
"type": "Entity",
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],
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},
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"id": "PMID-9710600_T37",
"type": "Entity",
"text": [
"N-terminal regulatory serines"
],
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"id": "PMID-9710600_T38",
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],
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"id": "PMID-9710600_T39",
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],
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],
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"id": "PMID-9710600_T40",
"type": "Entity",
"text": [
"reporter gene"
],
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],
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},
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"id": "PMID-9710600_T41",
"type": "Entity",
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],
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],
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},
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"id": "PMID-9710600_T42",
"type": "Entity",
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"plasma membrane-proximal elements"
],
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},
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"id": "PMID-9710600_T43",
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],
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],
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"id": "PMID-9710600_T44",
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"NF-kappaB"
],
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],
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"id": "PMID-9710600_T45",
"type": "Entity",
"text": [
"NF-kappaB"
],
"offsets": [
[
2062,
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],
"normalized": []
}
] | [] | [
{
"id": "PMID-9710600_1",
"entity_ids": [
"PMID-9710600_T2",
"PMID-9710600_T3"
]
},
{
"id": "PMID-9710600_2",
"entity_ids": [
"PMID-9710600_T9",
"PMID-9710600_T10"
]
},
{
"id": "PMID-9710600_3",
"entity_ids": [
"PMID-9710600_T13",
"PMID-9710600_T14"
]
},
{
"id": "PMID-9710600_4",
"entity_ids": [
"PMID-9710600_T22",
"PMID-9710600_T23"
]
}
] | [
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"id": "PMID-9710600_R1",
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},
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"id": "PMID-9710600_R2",
"type": "Protein-Component",
"arg1_id": "PMID-9710600_T12",
"arg2_id": "PMID-9710600_T37",
"normalized": []
}
] |
179 | PMID-8491377 | [
{
"id": "PMID-8491377__text",
"type": "abstract",
"text": [
"Cloning and functional characterization of early B-cell factor, a regulator of lymphocyte-specific gene expression. \nEarly B-cell factor (EBF) was identified previously as a tissue-specific and differentiation stage-specific DNA-binding protein that participates in the regulation of the pre-B and B lymphocyte-specific mb-1 gene. Partial amino acid sequences obtained from purified EBF were used to isolate cDNA clones, which by multiple criteria encode EBF. The recombinant polypeptide formed sequence-specific complexes with the EBF-binding site in the mb-1 promoter. The cDNA hybridized to multiple transcripts in pre-B and B-cell lines, but transcripts were not detected at significant levels in plasmacytoma, T-cell, and nonlymphoid cell lines. Expression of recombinant EBF in transfected nonlymphoid cells strongly activated transcription from reporter plasmids containing functional EBF-binding sites. Analysis of DNA binding by deletion mutants of EBF identified an amino-terminal cysteine-rich DNA-binding domain lacking obvious sequence similarity to known transcription factors. DNA-binding assays with cotranslated wild-type and truncated forms of EBF indicated that the protein interacts with its site as a homodimer. Deletions delineated a carboxy-terminal dimerization region containing two repeats of 15 amino acids that show similarity with the dimerization domains of basic-helix-loop-helix proteins. Together, these data suggest that EBF represents a novel regulator of B lymphocyte-specific gene expression.\n"
],
"offsets": [
[
0,
1530
]
]
}
] | [
{
"id": "PMID-8491377_T1",
"type": "Protein",
"text": [
"early B-cell factor"
],
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[
43,
62
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],
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},
{
"id": "PMID-8491377_T2",
"type": "Protein",
"text": [
"Early B-cell factor"
],
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[
117,
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]
],
"normalized": []
},
{
"id": "PMID-8491377_T3",
"type": "Protein",
"text": [
"EBF"
],
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[
138,
141
]
],
"normalized": []
},
{
"id": "PMID-8491377_T4",
"type": "Protein",
"text": [
"mb-1"
],
"offsets": [
[
320,
324
]
],
"normalized": []
},
{
"id": "PMID-8491377_T5",
"type": "Protein",
"text": [
"EBF"
],
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[
383,
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]
],
"normalized": []
},
{
"id": "PMID-8491377_T6",
"type": "Protein",
"text": [
"EBF"
],
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[
455,
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],
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},
{
"id": "PMID-8491377_T7",
"type": "Protein",
"text": [
"EBF"
],
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[
532,
535
]
],
"normalized": []
},
{
"id": "PMID-8491377_T8",
"type": "Protein",
"text": [
"mb-1"
],
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[
556,
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]
],
"normalized": []
},
{
"id": "PMID-8491377_T9",
"type": "Protein",
"text": [
"EBF"
],
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[
777,
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]
],
"normalized": []
},
{
"id": "PMID-8491377_T10",
"type": "Protein",
"text": [
"EBF"
],
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[
892,
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],
"normalized": []
},
{
"id": "PMID-8491377_T11",
"type": "Protein",
"text": [
"EBF"
],
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[
958,
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},
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"id": "PMID-8491377_T12",
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"text": [
"EBF"
],
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[
1162,
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],
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},
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"id": "PMID-8491377_T13",
"type": "Protein",
"text": [
"EBF"
],
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[
1455,
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],
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},
{
"id": "PMID-8491377_T14",
"type": "Entity",
"text": [
"DNA"
],
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[
225,
228
]
],
"normalized": []
},
{
"id": "PMID-8491377_T15",
"type": "Entity",
"text": [
"recombinant polypeptide"
],
"offsets": [
[
464,
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]
],
"normalized": []
},
{
"id": "PMID-8491377_T16",
"type": "Entity",
"text": [
"-binding site"
],
"offsets": [
[
535,
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]
],
"normalized": []
},
{
"id": "PMID-8491377_T17",
"type": "Entity",
"text": [
"promoter"
],
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[
561,
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],
"normalized": []
},
{
"id": "PMID-8491377_T18",
"type": "Entity",
"text": [
"-binding sites"
],
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[
895,
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]
],
"normalized": []
},
{
"id": "PMID-8491377_T19",
"type": "Entity",
"text": [
"amino-terminal cysteine-rich DNA-binding domain"
],
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[
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]
],
"normalized": []
},
{
"id": "PMID-8491377_T20",
"type": "Entity",
"text": [
"carboxy-terminal dimerization region"
],
"offsets": [
[
1256,
1292
]
],
"normalized": []
},
{
"id": "PMID-8491377_T21",
"type": "Entity",
"text": [
"15 amino acids"
],
"offsets": [
[
1319,
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]
],
"normalized": []
},
{
"id": "PMID-8491377_T22",
"type": "Entity",
"text": [
"dimerization domains"
],
"offsets": [
[
1364,
1384
]
],
"normalized": []
}
] | [] | [
{
"id": "PMID-8491377_1",
"entity_ids": [
"PMID-8491377_T2",
"PMID-8491377_T3"
]
}
] | [
{
"id": "PMID-8491377_R1",
"type": "Protein-Component",
"arg1_id": "PMID-8491377_T8",
"arg2_id": "PMID-8491377_T16",
"normalized": []
},
{
"id": "PMID-8491377_R2",
"type": "Protein-Component",
"arg1_id": "PMID-8491377_T8",
"arg2_id": "PMID-8491377_T17",
"normalized": []
},
{
"id": "PMID-8491377_R3",
"type": "Protein-Component",
"arg1_id": "PMID-8491377_T11",
"arg2_id": "PMID-8491377_T19",
"normalized": []
}
] |
180 | PMID-9845517 | [
{
"id": "PMID-9845517__text",
"type": "abstract",
"text": [
"Stat6 inhibits human interleukin-4 promoter activity in T cells. \nThe differentiation of naive T-helper (Th) cells into cytokine-secreting effector Th cells requires exposure to multiple signals, including exogenous cytokines. Interleukin-4 (IL-4) plays a major role in this process by promoting the differentiation of IL-4-secreting Th2 cells. In Th2 cells, IL-4 gene expression is tightly controlled at the level of transcription by the coordinated binding of multiple transcription factors to regulatory elements in the proximal promoter region. Nuclear factor of activated T cell (NFAT) family members play a critical role in regulating IL-4 transcription and interact with up to five sequences (termed P0 through P4) in the IL-4 promoter. The molecular mechanisms by which IL-4 induces expression of the IL-4 gene are not known, although the IL-4-activated transcription factor signal transducer and activator of transcription 6 (Stat6) is required for this effect. We report here that Stat6 interacts with three binding sites in the human IL-4 promoter by electrophoretic mobility shift assays. These sites overlap the P1, P2, and P4 NFAT elements. To investigate the role of Stat6 in regulating IL-4 transcription, we used Stat6-deficient Jurkat T cells with different intact IL-4 promoter constructs in cotransfection assays. We show that, whereas a multimerized response element from the germline IgE promoter was highly induced by IL-4 in Stat6-expressing Jurkat cells, the intact human IL-4 promoter was repressed under similar conditions. We conclude that the function of Stat6 is highly dependent on promoter context and that this factor promotes IL-4 gene expression in an indirect manner.\n"
],
"offsets": [
[
0,
1704
]
]
}
] | [
{
"id": "PMID-9845517_T1",
"type": "Protein",
"text": [
"Stat6"
],
"offsets": [
[
0,
5
]
],
"normalized": []
},
{
"id": "PMID-9845517_T2",
"type": "Protein",
"text": [
"interleukin-4"
],
"offsets": [
[
21,
34
]
],
"normalized": []
},
{
"id": "PMID-9845517_T3",
"type": "Protein",
"text": [
"Interleukin-4"
],
"offsets": [
[
227,
240
]
],
"normalized": []
},
{
"id": "PMID-9845517_T4",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
242,
246
]
],
"normalized": []
},
{
"id": "PMID-9845517_T5",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
319,
323
]
],
"normalized": []
},
{
"id": "PMID-9845517_T6",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
359,
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]
],
"normalized": []
},
{
"id": "PMID-9845517_T7",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
641,
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]
],
"normalized": []
},
{
"id": "PMID-9845517_T8",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
729,
733
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},
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"id": "PMID-9845517_T9",
"type": "Protein",
"text": [
"IL-4"
],
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[
778,
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"normalized": []
},
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"id": "PMID-9845517_T10",
"type": "Protein",
"text": [
"IL-4"
],
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[
809,
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],
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},
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"id": "PMID-9845517_T11",
"type": "Protein",
"text": [
"IL-4"
],
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[
847,
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],
"normalized": []
},
{
"id": "PMID-9845517_T12",
"type": "Protein",
"text": [
"signal transducer and activator of transcription 6"
],
"offsets": [
[
883,
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991,
996
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"id": "PMID-9845517_T15",
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"id": "PMID-9845517_T19",
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1283,
1287
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"id": "PMID-9845517_T20",
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1441,
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"id": "PMID-9845517_T21",
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1449,
1454
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"id": "PMID-9845517_T22",
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1497,
1501
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"id": "PMID-9845517_T23",
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1584,
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"id": "PMID-9845517_T24",
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"id": "PMID-9845517_T25",
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"id": "PMID-9845517_T31",
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"id": "PMID-9845517_T32",
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],
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"id": "PMID-9845517_T33",
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"multimerized response element"
],
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1358,
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"id": "PMID-9845517_T34",
"type": "Entity",
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"germline IgE promoter"
],
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"id": "PMID-9845517_T35",
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"id": "PMID-9845517_T36",
"type": "Entity",
"text": [
"promoter context"
],
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1613,
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}
] | [] | [
{
"id": "PMID-9845517_1",
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"PMID-9845517_T3",
"PMID-9845517_T4"
]
},
{
"id": "PMID-9845517_2",
"entity_ids": [
"PMID-9845517_T12",
"PMID-9845517_T13"
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}
] | [
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},
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"type": "Protein-Component",
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},
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"type": "Protein-Component",
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"arg2_id": "PMID-9845517_T27",
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"type": "Protein-Component",
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"arg2_id": "PMID-9845517_T28",
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},
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"type": "Protein-Component",
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},
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"type": "Protein-Component",
"arg1_id": "PMID-9845517_T22",
"arg2_id": "PMID-9845517_T35",
"normalized": []
},
{
"id": "PMID-9845517_R7",
"type": "Protein-Component",
"arg1_id": "PMID-9845517_T23",
"arg2_id": "PMID-9845517_T36",
"normalized": []
}
] |
181 | PMID-8479911 | [
{
"id": "PMID-8479911__text",
"type": "abstract",
"text": [
"Cell-specific expression of helix-loop-helix transcription factors encoded by the E2A gene. \nThe E2A gene encodes transcription factors of the helix-loop-helix family that are implicated in cell-specific gene expression as part of dimeric complexes that interact with E box enhancer elements. It has previously been shown that transcripts of the E2A gene can be detected in a wide range of cell types. We have now examined expression of the mouse E2A gene at the protein level using polyclonal antisera directed against distinct portions of the E2A protein to probe blots of cellular extracts. A 73 kDa protein was identified by this analysis: this protein is highly enriched in cell lines of B lymphoid origin as compared to pancreatic beta-cells and fibroblast cells. The detection of this protein selectively in extracts of lymphoid cells correlates with the presence of the E box-binding activity LEF1/BCF1 in these cells; this binding activity was previously shown to be efficiently recognized by antiserum directed against E2A gene products. Transfection of cells with full length E2A cDNA leads to appearance of protein co-migrating with the 73 kDa protein on SDS gel electrophoresis and co-migrating with LEF1/BCF1 on mobility shift analysis. Our results are consistent with the view that the DNA-binding activity LEF1/BCF1 is a homodimer of E2A proteins; the selective appearance of this putative cell-specific transcription factor in B lymphoid cells seems to be attributable, at least in part, to the elevated E2A protein concentrations in these cells.\n"
],
"offsets": [
[
0,
1564
]
]
}
] | [
{
"id": "PMID-8479911_T1",
"type": "Protein",
"text": [
"E2A"
],
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[
82,
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]
],
"normalized": []
},
{
"id": "PMID-8479911_T2",
"type": "Protein",
"text": [
"E2A"
],
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[
97,
100
]
],
"normalized": []
},
{
"id": "PMID-8479911_T3",
"type": "Protein",
"text": [
"E2A"
],
"offsets": [
[
346,
349
]
],
"normalized": []
},
{
"id": "PMID-8479911_T4",
"type": "Protein",
"text": [
"E2A"
],
"offsets": [
[
447,
450
]
],
"normalized": []
},
{
"id": "PMID-8479911_T5",
"type": "Protein",
"text": [
"E2A"
],
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[
545,
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]
],
"normalized": []
},
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"id": "PMID-8479911_T6",
"type": "Protein",
"text": [
"E2A"
],
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1029,
1032
]
],
"normalized": []
},
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"id": "PMID-8479911_T7",
"type": "Protein",
"text": [
"E2A"
],
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1087,
1090
]
],
"normalized": []
},
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"id": "PMID-8479911_T8",
"type": "Protein",
"text": [
"E2A"
],
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1350,
1353
]
],
"normalized": []
},
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"id": "PMID-8479911_T9",
"type": "Protein",
"text": [
"E2A"
],
"offsets": [
[
1521,
1524
]
],
"normalized": []
},
{
"id": "PMID-8479911_T10",
"type": "Entity",
"text": [
"dimeric complexes"
],
"offsets": [
[
231,
248
]
],
"normalized": []
},
{
"id": "PMID-8479911_T11",
"type": "Entity",
"text": [
"E box enhancer elements"
],
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[
268,
291
]
],
"normalized": []
},
{
"id": "PMID-8479911_T12",
"type": "Entity",
"text": [
"E box"
],
"offsets": [
[
878,
883
]
],
"normalized": []
},
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"id": "PMID-8479911_T13",
"type": "Entity",
"text": [
"LEF1/BCF1"
],
"offsets": [
[
901,
910
]
],
"normalized": []
},
{
"id": "PMID-8479911_T14",
"type": "Entity",
"text": [
"LEF1/BCF1"
],
"offsets": [
[
1213,
1222
]
],
"normalized": []
},
{
"id": "PMID-8479911_T15",
"type": "Entity",
"text": [
"LEF1/BCF1"
],
"offsets": [
[
1322,
1331
]
],
"normalized": []
},
{
"id": "PMID-8479911_T16",
"type": "Entity",
"text": [
"homodimer"
],
"offsets": [
[
1337,
1346
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "PMID-8479911_R1",
"type": "Subunit-Complex",
"arg1_id": "PMID-8479911_T2",
"arg2_id": "PMID-8479911_T10",
"normalized": []
},
{
"id": "PMID-8479911_R2",
"type": "Subunit-Complex",
"arg1_id": "PMID-8479911_T8",
"arg2_id": "PMID-8479911_T15",
"normalized": []
},
{
"id": "PMID-8479911_R3",
"type": "Subunit-Complex",
"arg1_id": "PMID-8479911_T8",
"arg2_id": "PMID-8479911_T16",
"normalized": []
}
] |
182 | PMID-7848921 | [
{
"id": "PMID-7848921__text",
"type": "abstract",
"text": [
"Overexpression of protein kinase C-zeta stimulates leukemic cell differentiation. \nA function for protein kinase C-zeta (PKC-zeta), a member of the phorbol ester nonresponsive atypical protein kinase C subfamily, in modulating differentiation was examined in the leukemic U937 cell. Transfected U937 cells stably overexpressing PKC-zeta displayed a longer doubling time, lower saturation density at confluency, and an increase in adherence to plastic as compared to control cells. PKC-zeta cells expressed a more differentiated phenotype as assessed by changes in morphology, surface antigen expression, and lysosomal enzyme activities and were distinct from parental U937 cells stimulated to differentiate by exposure to phorbol esters. In contrast to parental U937 cells, PKC-zeta cells constitutively expressed mRNA transcripts for c-jun and a low mobility AP-1 binding activity. Thus, PKC-zeta overexpression stimulates a type of phenotypic differentiation that differs significantly from maturation occurring upon activation of other PKC subfamilies induced by phorbol ester treatment. Increased expression of the c-jun protooncogene and an increase in AP-1 binding activity in PKC-zeta cells provides a potential mechanism for explaining the altered differentiation status of this cell.\n"
],
"offsets": [
[
0,
1293
]
]
}
] | [
{
"id": "PMID-7848921_T1",
"type": "Protein",
"text": [
"protein kinase C-zeta"
],
"offsets": [
[
18,
39
]
],
"normalized": []
},
{
"id": "PMID-7848921_T2",
"type": "Protein",
"text": [
"protein kinase C-zeta"
],
"offsets": [
[
98,
119
]
],
"normalized": []
},
{
"id": "PMID-7848921_T3",
"type": "Protein",
"text": [
"PKC-zeta"
],
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[
121,
129
]
],
"normalized": []
},
{
"id": "PMID-7848921_T4",
"type": "Protein",
"text": [
"PKC-zeta"
],
"offsets": [
[
328,
336
]
],
"normalized": []
},
{
"id": "PMID-7848921_T5",
"type": "Protein",
"text": [
"PKC-zeta"
],
"offsets": [
[
481,
489
]
],
"normalized": []
},
{
"id": "PMID-7848921_T6",
"type": "Protein",
"text": [
"PKC-zeta"
],
"offsets": [
[
774,
782
]
],
"normalized": []
},
{
"id": "PMID-7848921_T7",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
835,
840
]
],
"normalized": []
},
{
"id": "PMID-7848921_T8",
"type": "Protein",
"text": [
"PKC-zeta"
],
"offsets": [
[
889,
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]
],
"normalized": []
},
{
"id": "PMID-7848921_T9",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
1119,
1124
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],
"normalized": []
},
{
"id": "PMID-7848921_T10",
"type": "Protein",
"text": [
"PKC-zeta"
],
"offsets": [
[
1183,
1191
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],
"normalized": []
},
{
"id": "PMID-7848921_T11",
"type": "Entity",
"text": [
"AP-1"
],
"offsets": [
[
860,
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]
],
"normalized": []
},
{
"id": "PMID-7848921_T12",
"type": "Entity",
"text": [
"AP-1"
],
"offsets": [
[
1158,
1162
]
],
"normalized": []
}
] | [] | [
{
"id": "PMID-7848921_1",
"entity_ids": [
"PMID-7848921_T2",
"PMID-7848921_T3"
]
}
] | [] |
183 | PMID-7522304 | [
{
"id": "PMID-7522304__text",
"type": "abstract",
"text": [
"Calcium signalling in T cells stimulated by a cyclophilin B-binding protein. \nThe immunosuppressant drug cyclosporin A blocks a calcium-dependent signal from the T-cell receptor (TCR) that normally leads to T-cell activation. When bound to cyclophilin, cyclosporin A binds and inactivates the key signalling intermediate calcineurin. To identify potential cellular homologues of cyclosporin A that might regulate calcium signalling, we have cloned human genes encoding cyclophilin B-binding-proteins using the yeast two-hybrid system. One gene product, when overexpressed in Jurkat T cells, specifically induced transcription from the interleukin-2 enhancer, by activating the T-cell-specific transcription factors NF-AT and NF-IL2A. This protein, termed calcium-signal modulating cyclophilin ligand (CAML), acts downstream of the TCR and upstream of calcineurin by causing an influx of calcium. CAML appears to be a new participant in the calcium-signal transduction pathway, implicating cyclophilin B in calcium signalling, even in the absence of cyclosporin.\n"
],
"offsets": [
[
0,
1062
]
]
}
] | [
{
"id": "PMID-7522304_T1",
"type": "Protein",
"text": [
"cyclophilin B"
],
"offsets": [
[
46,
59
]
],
"normalized": []
},
{
"id": "PMID-7522304_T2",
"type": "Protein",
"text": [
"cyclophilin B"
],
"offsets": [
[
469,
482
]
],
"normalized": []
},
{
"id": "PMID-7522304_T3",
"type": "Protein",
"text": [
"interleukin-2"
],
"offsets": [
[
635,
648
]
],
"normalized": []
},
{
"id": "PMID-7522304_T4",
"type": "Protein",
"text": [
"calcium-signal modulating cyclophilin ligand"
],
"offsets": [
[
755,
799
]
],
"normalized": []
},
{
"id": "PMID-7522304_T5",
"type": "Protein",
"text": [
"CAML"
],
"offsets": [
[
801,
805
]
],
"normalized": []
},
{
"id": "PMID-7522304_T6",
"type": "Protein",
"text": [
"CAML"
],
"offsets": [
[
896,
900
]
],
"normalized": []
},
{
"id": "PMID-7522304_T7",
"type": "Protein",
"text": [
"cyclophilin B"
],
"offsets": [
[
989,
1002
]
],
"normalized": []
},
{
"id": "PMID-7522304_T8",
"type": "Entity",
"text": [
"enhancer"
],
"offsets": [
[
649,
657
]
],
"normalized": []
}
] | [] | [
{
"id": "PMID-7522304_1",
"entity_ids": [
"PMID-7522304_T4",
"PMID-7522304_T5"
]
}
] | [
{
"id": "PMID-7522304_R1",
"type": "Protein-Component",
"arg1_id": "PMID-7522304_T3",
"arg2_id": "PMID-7522304_T8",
"normalized": []
}
] |
184 | PMID-9009221 | [
{
"id": "PMID-9009221__text",
"type": "abstract",
"text": [
"Nuclear factor-kappaB activation in human monocytes stimulated with lipopolysaccharide is inhibited by fibroblast conditioned medium and exogenous PGE2. \nThe nuclear factor kappaB (NF-kappaB) is thought to be crucially involved in the gene activation of several cytokines, including tumor necrosis factor alpha (TNF). Previously, we showed that fibroblast conditioned medium (FCM) is able to inhibit both TNF mRNA accumulation and protein release in peripheral blood-derived human monocytes (PBM) stimulated with lipopolysaccharide (LPS). In this study we have investigated the effect of FCM on the LPS-induced DNA-binding activity of NF-kappaB, by means of electrophoretic shift assay (EMSA). We provide evidence that FCM strongly inhibits the LPS-induced NF-kappaB activation in PBM. Furthermore, we show that exogenous PGE2 mimics the NF-kappaB inhibitory effect of FCM. On the other hand, FCM produced in the presence of indomethacin does not inhibit NF-kappaB activation by LPS. Our results lend further support to the hypothesis that inflammatory and immune responses of monocytes/macrophages may be modulated at the molecular level by signals originating from tissue structural cells such as fibroblasts.\n"
],
"offsets": [
[
0,
1212
]
]
}
] | [
{
"id": "PMID-9009221_T1",
"type": "Protein",
"text": [
"tumor necrosis factor alpha"
],
"offsets": [
[
283,
310
]
],
"normalized": []
},
{
"id": "PMID-9009221_T2",
"type": "Protein",
"text": [
"TNF"
],
"offsets": [
[
312,
315
]
],
"normalized": []
},
{
"id": "PMID-9009221_T3",
"type": "Protein",
"text": [
"TNF"
],
"offsets": [
[
405,
408
]
],
"normalized": []
},
{
"id": "PMID-9009221_T4",
"type": "Entity",
"text": [
"Nuclear factor-kappaB"
],
"offsets": [
[
0,
21
]
],
"normalized": []
},
{
"id": "PMID-9009221_T5",
"type": "Entity",
"text": [
"nuclear factor kappaB"
],
"offsets": [
[
158,
179
]
],
"normalized": []
},
{
"id": "PMID-9009221_T6",
"type": "Entity",
"text": [
"NF-kappaB"
],
"offsets": [
[
181,
190
]
],
"normalized": []
},
{
"id": "PMID-9009221_T7",
"type": "Entity",
"text": [
"DNA"
],
"offsets": [
[
611,
614
]
],
"normalized": []
},
{
"id": "PMID-9009221_T8",
"type": "Entity",
"text": [
"NF-kappaB"
],
"offsets": [
[
635,
644
]
],
"normalized": []
},
{
"id": "PMID-9009221_T9",
"type": "Entity",
"text": [
"NF-kappaB"
],
"offsets": [
[
757,
766
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],
"normalized": []
},
{
"id": "PMID-9009221_T10",
"type": "Entity",
"text": [
"NF-kappaB"
],
"offsets": [
[
838,
847
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],
"normalized": []
},
{
"id": "PMID-9009221_T11",
"type": "Entity",
"text": [
"NF-kappaB"
],
"offsets": [
[
955,
964
]
],
"normalized": []
}
] | [] | [
{
"id": "PMID-9009221_1",
"entity_ids": [
"PMID-9009221_T1",
"PMID-9009221_T2"
]
}
] | [] |
185 | PMID-10022882 | [
{
"id": "PMID-10022882__text",
"type": "abstract",
"text": [
"Reactive oxygen intermediate-dependent NF-kappaB activation by interleukin-1beta requires 5-lipoxygenase or NADPH oxidase activity. \nWe previously reported that the role of reactive oxygen intermediates (ROIs) in NF-kappaB activation by proinflammatory cytokines was cell specific. However, the sources for ROIs in various cell types are yet to be determined and might include 5-lipoxygenase (5-LOX) and NADPH oxidase. 5-LOX and 5-LOX activating protein (FLAP) are coexpressed in lymphoid cells but not in monocytic or epithelial cells. Stimulation of lymphoid cells with interleukin-1beta (IL-1beta) led to ROI production and NF-kappaB activation, which could both be blocked by antioxidants or FLAP inhibitors, confirming that 5-LOX was the source of ROIs and was required for NF-kappaB activation in these cells. IL-1beta stimulation of epithelial cells did not generate any ROIs and NF-kappaB induction was not influenced by 5-LOX inhibitors. However, reintroduction of a functional 5-LOX system in these cells allowed ROI production and 5-LOX-dependent NF-kappaB activation. In monocytic cells, IL-1beta treatment led to a production of ROIs which is independent of the 5-LOX enzyme but requires the NADPH oxidase activity. This pathway involves the Rac1 and Cdc42 GTPases, two enzymes which are not required for NF-kappaB activation by IL-1beta in epithelial cells. In conclusion, three different cell-specific pathways lead to NF-kappaB activation by IL-1beta: a pathway dependent on ROI production by 5-LOX in lymphoid cells, an ROI- and 5-LOX-independent pathway in epithelial cells, and a pathway requiring ROI production by NADPH oxidase in monocytic cells.\n"
],
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0,
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"id": "PMID-10022882_T1",
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90,
104
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377,
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"id": "PMID-10022882_T10",
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816,
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"id": "PMID-10022882_T22",
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"id": "PMID-10022882_T23",
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"id": "PMID-10022882_T30",
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"id": "PMID-10022882_T31",
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"text": [
"NF-kappaB"
],
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1434,
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],
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}
] | [] | [
{
"id": "PMID-10022882_1",
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"PMID-10022882_T3",
"PMID-10022882_T4"
]
},
{
"id": "PMID-10022882_2",
"entity_ids": [
"PMID-10022882_T8",
"PMID-10022882_T9"
]
}
] | [] |
186 | PMID-10037138 | [
{
"id": "PMID-10037138__text",
"type": "abstract",
"text": [
"Differential expression and phosphorylation of CTCF, a c-myc transcriptional regulator, during differentiation of human myeloid cells. \nCTCF is a transcriptional repressor of the c-myc gene. Although CTCF has been characterized in some detail, there is very little information about the regulation of CTCF activity. Therefore we investigated CTCF expression and phosphorylation during induced differentiation of human myeloid leukemia cells. We found that: (i) both CTCF mRNA and protein are down-regulated during terminal differentiation in most cell lines tested; (ii) CTCF down-regulation is retarded and less pronounced than that of c-myc; (iii) CTCF protein is differentially phosphorylated and the phosphorylation profiles depend on the differentiation pathway. We concluded that CTCF expression and activity is controlled at transcriptional and post-transcriptional levels.\n"
],
"offsets": [
[
0,
881
]
]
}
] | [
{
"id": "PMID-10037138_T1",
"type": "Protein",
"text": [
"CTCF"
],
"offsets": [
[
47,
51
]
],
"normalized": []
},
{
"id": "PMID-10037138_T2",
"type": "Protein",
"text": [
"c-myc"
],
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[
55,
60
]
],
"normalized": []
},
{
"id": "PMID-10037138_T3",
"type": "Protein",
"text": [
"CTCF"
],
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136,
140
]
],
"normalized": []
},
{
"id": "PMID-10037138_T4",
"type": "Protein",
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"c-myc"
],
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179,
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]
],
"normalized": []
},
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"id": "PMID-10037138_T5",
"type": "Protein",
"text": [
"CTCF"
],
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[
200,
204
]
],
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},
{
"id": "PMID-10037138_T6",
"type": "Protein",
"text": [
"CTCF"
],
"offsets": [
[
301,
305
]
],
"normalized": []
},
{
"id": "PMID-10037138_T7",
"type": "Protein",
"text": [
"CTCF"
],
"offsets": [
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342,
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]
],
"normalized": []
},
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"id": "PMID-10037138_T8",
"type": "Protein",
"text": [
"CTCF"
],
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466,
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]
],
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},
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"id": "PMID-10037138_T9",
"type": "Protein",
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"CTCF"
],
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571,
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]
],
"normalized": []
},
{
"id": "PMID-10037138_T10",
"type": "Protein",
"text": [
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],
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637,
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]
],
"normalized": []
},
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"id": "PMID-10037138_T11",
"type": "Protein",
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},
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"id": "PMID-10037138_T12",
"type": "Protein",
"text": [
"CTCF"
],
"offsets": [
[
786,
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]
],
"normalized": []
}
] | [] | [] | [] |
187 | PMID-8759721 | [
{
"id": "PMID-8759721__text",
"type": "abstract",
"text": [
"Inhibition of transcription factor Stat1 activity in mononuclear cell cultures and T cells by the cyclic AMP signaling pathway. \nActivation of T cells results in a cascade of gene activation and subsequent proliferation and differentiation into effector phenotypes. The regulation of transcription factors belonging to the signal transducer and activator of transcription (STAT) family was analyzed in PHA-activated mononuclear cells and in purified T cells activated by cross-linking cell surface CD3. Cell activation resulted in a delayed induction of STAT DNA-binding activity, which was sustained for several days, was composed predominantly of Stat1 and Stat3, and was blocked by cycloheximide and actinomycin D. Increased Stat1 and Stat3 mRNA and protein levels were detected, respectively 4 and 24 h after activation. Stimulation of the cAMP signal transduction pathway, which skews cytokine production toward a Th2 pattern, resulted in the preferential suppression of Stat1 activity. cAMP inhibited the induction of expression of IL-2 receptor components, but did not inhibit IL-4 receptor alpha-chain and CD69 expression or the induction of activator protein 1 transcription factors. cAMP signaling inhibited Stat1 at several different levels, including suppression of DNA binding and down-regulation of Stat1 protein and mRNA levels. Our results demonstrate the regulation of STAT activity by a signaling pathway that regulates the T cell functional phenotype and is distinct from the cytokine-activated Janus kinase-STAT signaling pathway.\n"
],
"offsets": [
[
0,
1551
]
]
}
] | [
{
"id": "PMID-8759721_T1",
"type": "Protein",
"text": [
"Stat1"
],
"offsets": [
[
35,
40
]
],
"normalized": []
},
{
"id": "PMID-8759721_T2",
"type": "Protein",
"text": [
"PHA"
],
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[
402,
405
]
],
"normalized": []
},
{
"id": "PMID-8759721_T3",
"type": "Protein",
"text": [
"Stat1"
],
"offsets": [
[
649,
654
]
],
"normalized": []
},
{
"id": "PMID-8759721_T4",
"type": "Protein",
"text": [
"Stat3"
],
"offsets": [
[
659,
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]
],
"normalized": []
},
{
"id": "PMID-8759721_T5",
"type": "Protein",
"text": [
"Stat1"
],
"offsets": [
[
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]
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"normalized": []
},
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"id": "PMID-8759721_T6",
"type": "Protein",
"text": [
"IL-2"
],
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[
1038,
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]
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},
{
"id": "PMID-8759721_T7",
"type": "Protein",
"text": [
"IL-4 receptor alpha-chain"
],
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]
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},
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"id": "PMID-8759721_T8",
"type": "Protein",
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],
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"id": "PMID-8759721_T9",
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},
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"id": "PMID-8759721_T10",
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"id": "PMID-8759721_T11",
"type": "Entity",
"text": [
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],
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98,
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},
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"id": "PMID-8759721_T12",
"type": "Entity",
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],
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485,
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},
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"id": "PMID-8759721_T13",
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},
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"id": "PMID-8759721_T14",
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"cAMP"
],
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992,
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},
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"id": "PMID-8759721_T15",
"type": "Entity",
"text": [
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],
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"normalized": []
},
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"id": "PMID-8759721_T16",
"type": "Entity",
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],
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},
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"id": "PMID-8759721_T17",
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"text": [
"cAMP"
],
"offsets": [
[
1193,
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],
"normalized": []
}
] | [] | [] | [] |
188 | PMID-7664781 | [
{
"id": "PMID-7664781__text",
"type": "abstract",
"text": [
"Interleukin-2 promoter activity in Epstein-Barr virus-transformed B lymphocytes is controlled by nuclear factor-chi B. \nThe regulation of interleukin (IL)-2 gene expression has been investigated mainly in T lymphocytes, the predominant producers of IL-2. However, B cells can also synthesize IL-2. In the present study we analyzed the control of IL-2 promoter activity in Epstein-Barr virus (EBV)-transformed B cell clones which are capable of secreting IL-2 at a low level after stimulation with phorbol 12-myristate 13-acetate and the Ca2+ ionophore ionomycin. Transient transfections using reporter constructs with multiples of transcription factor binding sites from the IL-2 promoter [distal nuclear factor (NF)-AT, proximal NF-AT, AP-1/Octamer (UPS) or NF-chi B (TCEd) sites] were performed. In EBV-transformed B clones, the chi B site exerted the strongest inducible activity; the NF-AT binding sites showed either no or only weak activity compared to Jurkat T cells. An IL-2 promoter bearing a defective NF-chi B site was completely inactive in EBV-transformed B cells, while it still had activity in Jurkat T cells. In seven EBV-B cell clones or lines differing in their capacity to secrete IL-2, the activity of the IL-2 promoter correlated well with the status of IL-2 secretion. Similarly, a human immunodeficiency virus promoter, whose activity is controlled through chi B factors, was found to be active in the IL-2 producing EBV-B cells, but inactive in the non-IL-2-producing cells. Electrophoretic mobility shift assays using protein extracts from EBV-B cells and the IL-2 NF-chi B probe revealed the constitutive generation of chi B complexes in IL-2-secreting cells consisting mainly of heterodimeric p50/p65 complexes. A weaker chi B complex formation and faster-migrating complexes were detected in non-IL-2-secreting cells. These results demonstrate that the IL-2 NF-chi B site is indispensable for the activity of the IL-2 promoter in EBV-transformed B cells, whereas other transcription factors appear to be less important for IL-2 expression in these cells.\n"
],
"offsets": [
[
0,
2083
]
]
}
] | [
{
"id": "PMID-7664781_T1",
"type": "Protein",
"text": [
"Interleukin-2"
],
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[
0,
13
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],
"normalized": []
},
{
"id": "PMID-7664781_T2",
"type": "Protein",
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],
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[
138,
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"normalized": []
},
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"id": "PMID-7664781_T3",
"type": "Protein",
"text": [
"IL-2"
],
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[
249,
253
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"normalized": []
},
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"id": "PMID-7664781_T4",
"type": "Protein",
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],
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[
292,
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"normalized": []
},
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"id": "PMID-7664781_T5",
"type": "Protein",
"text": [
"IL-2"
],
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[
346,
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]
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"normalized": []
},
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"id": "PMID-7664781_T6",
"type": "Protein",
"text": [
"IL-2"
],
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[
454,
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"normalized": []
},
{
"id": "PMID-7664781_T7",
"type": "Protein",
"text": [
"IL-2"
],
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675,
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},
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"id": "PMID-7664781_T8",
"type": "Protein",
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"IL-2"
],
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978,
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},
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"id": "PMID-7664781_T9",
"type": "Protein",
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"IL-2"
],
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1200,
1204
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},
{
"id": "PMID-7664781_T10",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1226,
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"normalized": []
},
{
"id": "PMID-7664781_T11",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1275,
1279
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"normalized": []
},
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"id": "PMID-7664781_T12",
"type": "Protein",
"text": [
"IL-2"
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1425,
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},
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"id": "PMID-7664781_T13",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1477,
1481
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},
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"id": "PMID-7664781_T14",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1585,
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},
{
"id": "PMID-7664781_T15",
"type": "Protein",
"text": [
"IL-2"
],
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[
1664,
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"normalized": []
},
{
"id": "PMID-7664781_T16",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
1720,
1723
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],
"normalized": []
},
{
"id": "PMID-7664781_T17",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
1724,
1727
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],
"normalized": []
},
{
"id": "PMID-7664781_T18",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1824,
1828
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],
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},
{
"id": "PMID-7664781_T19",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1881,
1885
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],
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},
{
"id": "PMID-7664781_T20",
"type": "Protein",
"text": [
"IL-2"
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"offsets": [
[
1941,
1945
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},
{
"id": "PMID-7664781_T21",
"type": "Protein",
"text": [
"IL-2"
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"offsets": [
[
2051,
2055
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"normalized": []
},
{
"id": "PMID-7664781_T22",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
14,
22
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"normalized": []
},
{
"id": "PMID-7664781_T23",
"type": "Entity",
"text": [
"nuclear factor-chi B"
],
"offsets": [
[
97,
117
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},
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] |
189 | PMID-2127692 | [
{
"id": "PMID-2127692__text",
"type": "abstract",
"text": [
"Transcriptional down-regulation of c-myc expression by protein synthesis-dependent and -independent pathways in a human T lymphoblastic tumor cell line. \nWe show that in the human T lymphoblastic tumor cell line Molt4 c-myc mRNA and protein expression is down-regulated after exposure to dimethyl sulfoxide, to phorbol myristate acetate, or to the calcium ionophore A23187, which raises the intracellular calcium concentration. A block to RNA elongation is largely responsible for decreased c-myc transcription. Although negative regulation by dimethyl sulfoxide takes place even when protein synthesis is inhibited by cycloheximide, the phorbol myristate acetate effect is blocked to some extent only by cycloheximide. The calcium ionophore-induced c-myc suppression, however, strictly requires de novo protein synthesis. Therefore, two different negative regulatory pathways are involved in c-myc regulation: one which is independent and one which depends on de novo protein synthesis. The latter one appears to be mediated by a rapidly calcium-dependent induced gene product.\n"
],
"offsets": [
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0,
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]
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"id": "PMID-2127692_T4",
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"id": "PMID-2127692_T5",
"type": "Protein",
"text": [
"c-myc"
],
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893,
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]
],
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}
] | [] | [] | [] |
190 | PMID-1419905 | [
{
"id": "PMID-1419905__text",
"type": "abstract",
"text": [
"Activation of NF-kappa B by interleukin 2 in human blood monocytes. \nWe report here that interleukin 2 (IL-2) acts on human blood monocytes by enhancing binding activity of the transcription factor NF-kappa B to its consensus sequence in the 5' regulatory enhancer region of the IL-2 receptor alpha chain (p55). Similarly, IL-2 activates NF-kappa B in the human monocytic cell line U 937, but not in resting human T-cells. This effect is detectable within 15 min and peaks 1 h after exposure to IL-2. Enhanced NF-kappa B binding activity is followed by functional activation in that inducibility of the IL-2 receptor alpha chain is mediated by enhanced NF-kappa B binding and that a heterologous promoter containing the NF-kappa B consensus sequence (-291 to -245) of the IL-2 receptor alpha chain gene is activated. In addition, IL-2 is capable of increasing transcript levels of the p50 gene coding for the p50 subunit of the NF-kappa B transcription factor, whereas mRNA levels of the p65 NF-kappa B gene remained unchanged.\n"
],
"offsets": [
[
0,
1028
]
]
}
] | [
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],
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],
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"id": "PMID-1419905_T3",
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"IL-2"
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},
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"id": "PMID-1419905_T4",
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"IL-2 receptor alpha chain"
],
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[
279,
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]
],
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},
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"id": "PMID-1419905_T5",
"type": "Protein",
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"p55"
],
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306,
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]
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},
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"id": "PMID-1419905_T6",
"type": "Protein",
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"IL-2"
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"id": "PMID-1419905_T7",
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"id": "PMID-1419905_T11",
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653,
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720,
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"id": "PMID-1419905_T22",
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],
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751,
763
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"id": "PMID-1419905_T23",
"type": "Entity",
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"NF-kappa B"
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"id": "PMID-1419905_T24",
"type": "Entity",
"text": [
"NF-kappa B gene"
],
"offsets": [
[
992,
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],
"normalized": []
}
] | [] | [
{
"id": "PMID-1419905_1",
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"PMID-1419905_T2",
"PMID-1419905_T3"
]
},
{
"id": "PMID-1419905_2",
"entity_ids": [
"PMID-1419905_T4",
"PMID-1419905_T5"
]
}
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"type": "Protein-Component",
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},
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"type": "Protein-Component",
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},
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"type": "Subunit-Complex",
"arg1_id": "PMID-1419905_T12",
"arg2_id": "PMID-1419905_T23",
"normalized": []
}
] |
191 | PMID-9716600 | [
{
"id": "PMID-9716600__text",
"type": "abstract",
"text": [
"Retinoic acid inhibits CD40 + interleukin-4-mediated IgE production in vitro. \nTo elucidate the role of retinoic acid (RA) in anti-CD40 + interleukin-4 (IL-4)-mediated B-cell activation, the effect of 10(-12) to 10(-6) mol/L RA was studied in anti-CD40 (1 microgram/mL) + IL-4 (5 ng/mL)-mediated proliferation and Ig synthesis by human peripheral blood mononuclear cells (PBMC) and B cells in healthy donors. Anti-CD40 + IL-4-mediated proliferation of PBMC and B cells was inhibited by RA in a dose-dependent manner, with maximal inhibition of 62% +/- 5% in PBMC and 55% +/- 4.4% in B cells by all-trans RA, and 58% +/- 6.7% and 51% +/- 4.7%, respectively by 13-cis RA. IgE synthesis was even more markedly inhibited by RA starting at concentrations of >10(-14) mol/L for B cells and >10(-10) mol/L for PBMC. Maximal inhibition of IgE production for B cells was at 10(-8) mol/L for all-trans RA (94% +/- 1.8%) and 96% +/- 3.2% for 13-cis RA. Low concentrations of RA inhibiting IgE synthesis (10(-10) mol/L) affected neither B-cell proliferation nor the production of IgA, IgG, and IgM. Elucidation of the mechanism involved in this inhibition of IgE production shows that epsilon germline transcription is decreased by RA, whereas production of interferon-gamma (IFN-gamma) was not enhanced in the presence of RA. To differentiate whether the RA effect was mediated by RA receptors alpha, beta, and gamma, the expression of the retinoic acid receptors (RAR) was examined by reverse transcriptase-polymerase chain reaction (RT-PCR). The data show that unstimulated human peripheral B cells express mRNA of the RA receptor alpha, beta, and gamma. Using retinoids with different receptor binding specificity (CD336, CD437, CD2019, CD367), dose-dependent inhibition of IgE synthesis was shown by all four derivates, but was most marked by an RA binding the alpha receptor with high specificity. Taken together, this study shows that RA inhibits IgE production of anti-CD40 + IL-4-stimulated B cells in vitro. Copyright 1998 by The American Society of Hematology.\n"
],
"offsets": [
[
0,
2060
]
]
}
] | [
{
"id": "PMID-9716600_T1",
"type": "Protein",
"text": [
"CD40"
],
"offsets": [
[
23,
27
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"normalized": []
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"id": "PMID-9716600_T2",
"type": "Protein",
"text": [
"interleukin-4"
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[
30,
43
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"id": "PMID-9716600_T3",
"type": "Protein",
"text": [
"CD40"
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131,
135
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"id": "PMID-9716600_T4",
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138,
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"id": "PMID-9716600_T5",
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153,
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"id": "PMID-9716600_T6",
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248,
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"id": "PMID-9716600_T7",
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272,
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"id": "PMID-9716600_T8",
"type": "Protein",
"text": [
"CD40"
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414,
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"id": "PMID-9716600_T9",
"type": "Protein",
"text": [
"IL-4"
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421,
425
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"id": "PMID-9716600_T10",
"type": "Protein",
"text": [
"interferon-gamma"
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[
1246,
1262
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"id": "PMID-9716600_T11",
"type": "Protein",
"text": [
"IFN-gamma"
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1264,
1273
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"id": "PMID-9716600_T12",
"type": "Protein",
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"RA receptors alpha"
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1370,
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"id": "PMID-9716600_T13",
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1390,
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1639,
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"id": "PMID-9716600_T20",
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"text": [
"epsilon germline"
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1173,
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}
] | [] | [
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"entity_ids": [
"PMID-9716600_T10",
"PMID-9716600_T11"
]
}
] | [] |
192 | PMID-7730624 | [
{
"id": "PMID-7730624__text",
"type": "abstract",
"text": [
"Activation of transcription by binding of NF-E1 (YY1) to a newly identified element in the first exon of the human DR alpha gene. \nA previously unrecognized element, located downstream of the start site of transcription in the first exon of the DR alpha gene, has been defined that enhances promoter activity up to eightfold in a position-dependent manner. Mutations in this DNA-binding site abolished binding of a nuclear factor in human B cell nuclear extract and decreased the activity of the DR alpha promoter to a basal level. Significant sequence homology of this element was found in the DNA of the DR beta, DP alpha and -beta, and DQ alpha genes, always located downstream of the transcriptional start site. The nuclear factor binds to the DR alpha and DP alpha element but not to the element in the DQ alpha gene. It was identified as NF-E1 (YY1). This protein, previously identified by its binding to the Ig kappa 3' enhancer and the Ig heavy chain mu E1 site, thus also appears to be quite important in the regulation of MHC class II gene expression.\n"
],
"offsets": [
[
0,
1062
]
]
}
] | [
{
"id": "PMID-7730624_T1",
"type": "Protein",
"text": [
"NF-E1"
],
"offsets": [
[
42,
47
]
],
"normalized": []
},
{
"id": "PMID-7730624_T2",
"type": "Protein",
"text": [
"YY1"
],
"offsets": [
[
49,
52
]
],
"normalized": []
},
{
"id": "PMID-7730624_T3",
"type": "Protein",
"text": [
"DR alpha"
],
"offsets": [
[
115,
123
]
],
"normalized": []
},
{
"id": "PMID-7730624_T4",
"type": "Protein",
"text": [
"DR alpha"
],
"offsets": [
[
245,
253
]
],
"normalized": []
},
{
"id": "PMID-7730624_T5",
"type": "Protein",
"text": [
"DR alpha"
],
"offsets": [
[
496,
504
]
],
"normalized": []
},
{
"id": "PMID-7730624_T6",
"type": "Protein",
"text": [
"DR beta"
],
"offsets": [
[
606,
613
]
],
"normalized": []
},
{
"id": "PMID-7730624_T7",
"type": "Protein",
"text": [
"DQ alpha"
],
"offsets": [
[
639,
647
]
],
"normalized": []
},
{
"id": "PMID-7730624_T8",
"type": "Protein",
"text": [
"DR alpha"
],
"offsets": [
[
748,
756
]
],
"normalized": []
},
{
"id": "PMID-7730624_T9",
"type": "Protein",
"text": [
"DP alpha"
],
"offsets": [
[
761,
769
]
],
"normalized": []
},
{
"id": "PMID-7730624_T10",
"type": "Protein",
"text": [
"DQ alpha"
],
"offsets": [
[
808,
816
]
],
"normalized": []
},
{
"id": "PMID-7730624_T11",
"type": "Protein",
"text": [
"NF-E1"
],
"offsets": [
[
844,
849
]
],
"normalized": []
},
{
"id": "PMID-7730624_T12",
"type": "Protein",
"text": [
"YY1"
],
"offsets": [
[
851,
854
]
],
"normalized": []
},
{
"id": "PMID-7730624_T13",
"type": "Entity",
"text": [
"element"
],
"offsets": [
[
157,
164
]
],
"normalized": []
},
{
"id": "PMID-7730624_T14",
"type": "Entity",
"text": [
"start site of transcription"
],
"offsets": [
[
192,
219
]
],
"normalized": []
},
{
"id": "PMID-7730624_T15",
"type": "Entity",
"text": [
"exon"
],
"offsets": [
[
233,
237
]
],
"normalized": []
},
{
"id": "PMID-7730624_T16",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
291,
299
]
],
"normalized": []
},
{
"id": "PMID-7730624_T17",
"type": "Entity",
"text": [
"DNA-binding site"
],
"offsets": [
[
375,
391
]
],
"normalized": []
},
{
"id": "PMID-7730624_T18",
"type": "Entity",
"text": [
"promoter"
],
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[
505,
513
]
],
"normalized": []
},
{
"id": "PMID-7730624_T19",
"type": "Entity",
"text": [
"element"
],
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[
570,
577
]
],
"normalized": []
},
{
"id": "PMID-7730624_T20",
"type": "Entity",
"text": [
"DP alpha"
],
"offsets": [
[
615,
623
]
],
"normalized": []
},
{
"id": "PMID-7730624_T21",
"type": "Entity",
"text": [
"beta"
],
"offsets": [
[
629,
633
]
],
"normalized": []
},
{
"id": "PMID-7730624_T22",
"type": "Entity",
"text": [
"transcriptional start site"
],
"offsets": [
[
688,
714
]
],
"normalized": []
},
{
"id": "PMID-7730624_T23",
"type": "Entity",
"text": [
"element"
],
"offsets": [
[
770,
777
]
],
"normalized": []
},
{
"id": "PMID-7730624_T24",
"type": "Entity",
"text": [
"element"
],
"offsets": [
[
793,
800
]
],
"normalized": []
},
{
"id": "PMID-7730624_T25",
"type": "Entity",
"text": [
"Ig kappa 3' enhancer"
],
"offsets": [
[
915,
935
]
],
"normalized": []
},
{
"id": "PMID-7730624_T26",
"type": "Entity",
"text": [
"Ig heavy chain mu E1 site"
],
"offsets": [
[
944,
969
]
],
"normalized": []
},
{
"id": "PMID-7730624_T27",
"type": "Entity",
"text": [
"Ig heavy chain"
],
"offsets": [
[
944,
958
]
],
"normalized": []
},
{
"id": "PMID-7730624_T28",
"type": "Entity",
"text": [
"MHC class II gene"
],
"offsets": [
[
1032,
1049
]
],
"normalized": []
}
] | [] | [
{
"id": "PMID-7730624_1",
"entity_ids": [
"PMID-7730624_T1",
"PMID-7730624_T2"
]
},
{
"id": "PMID-7730624_2",
"entity_ids": [
"PMID-7730624_T11",
"PMID-7730624_T12"
]
}
] | [
{
"id": "PMID-7730624_R1",
"type": "Protein-Component",
"arg1_id": "PMID-7730624_T4",
"arg2_id": "PMID-7730624_T15",
"normalized": []
},
{
"id": "PMID-7730624_R2",
"type": "Protein-Component",
"arg1_id": "PMID-7730624_T4",
"arg2_id": "PMID-7730624_T13",
"normalized": []
},
{
"id": "PMID-7730624_R3",
"type": "Protein-Component",
"arg1_id": "PMID-7730624_T4",
"arg2_id": "PMID-7730624_T14",
"normalized": []
},
{
"id": "PMID-7730624_R4",
"type": "Protein-Component",
"arg1_id": "PMID-7730624_T5",
"arg2_id": "PMID-7730624_T18",
"normalized": []
},
{
"id": "PMID-7730624_R5",
"type": "Protein-Component",
"arg1_id": "PMID-7730624_T6",
"arg2_id": "PMID-7730624_T22",
"normalized": []
},
{
"id": "PMID-7730624_R6",
"type": "Protein-Component",
"arg1_id": "PMID-7730624_T7",
"arg2_id": "PMID-7730624_T22",
"normalized": []
},
{
"id": "PMID-7730624_R7",
"type": "Protein-Component",
"arg1_id": "PMID-7730624_T6",
"arg2_id": "PMID-7730624_T19",
"normalized": []
},
{
"id": "PMID-7730624_R8",
"type": "Protein-Component",
"arg1_id": "PMID-7730624_T10",
"arg2_id": "PMID-7730624_T24",
"normalized": []
}
] |
193 | PMID-10206983 | [
{
"id": "PMID-10206983__text",
"type": "abstract",
"text": [
"Inhibition of T cell signaling by mitogen-activated protein kinase-targeted hematopoietic tyrosine phosphatase (HePTP). \nActivation of T lymphocytes to produce cytokines is regulated by the counterbalance of protein-tyrosine kinases and protein-tyrosine phosphatases, many of which have a high degree of substrate specificity because of physical association with their targets. Overexpression of hematopoietic protein-tyrosine phosphatase (HePTP) results in suppression of T lymphocyte activation as measured by T cell antigen receptor-induced activation of transcription factors binding to the 5' promoter of the interleukin-2 gene. Efforts to pinpoint the exact site of action and specificity of HePTP in the signaling cascade revealed that HePTP acts directly on the mitogen-activated protein (MAP) kinases Erk1 and 2 and consequently reduces the magnitude and duration of their catalytic activation in intact T cells. In contrast, HePTP had no effects on N-terminal c-Jun kinase or on events upstream of the MAP kinases. The specificity of HePTP correlated with its physical association through its noncatalytic N terminus with Erk and another MAP kinase, p38, but not Jnk or other proteins. We propose that HePTP plays a negative role in antigen receptor signaling by specifically regulating MAP kinases in the cytosol and at early time points of T cell activation before the activation-induced expression of nuclear dual-specific MAP kinase phosphatases.\n"
],
"offsets": [
[
0,
1461
]
]
}
] | [
{
"id": "PMID-10206983_T1",
"type": "Protein",
"text": [
"hematopoietic tyrosine phosphatase"
],
"offsets": [
[
76,
110
]
],
"normalized": []
},
{
"id": "PMID-10206983_T2",
"type": "Protein",
"text": [
"HePTP"
],
"offsets": [
[
112,
117
]
],
"normalized": []
},
{
"id": "PMID-10206983_T3",
"type": "Protein",
"text": [
"hematopoietic protein-tyrosine phosphatase"
],
"offsets": [
[
396,
438
]
],
"normalized": []
},
{
"id": "PMID-10206983_T4",
"type": "Protein",
"text": [
"HePTP"
],
"offsets": [
[
440,
445
]
],
"normalized": []
},
{
"id": "PMID-10206983_T5",
"type": "Protein",
"text": [
"interleukin-2"
],
"offsets": [
[
614,
627
]
],
"normalized": []
},
{
"id": "PMID-10206983_T6",
"type": "Protein",
"text": [
"HePTP"
],
"offsets": [
[
698,
703
]
],
"normalized": []
},
{
"id": "PMID-10206983_T7",
"type": "Protein",
"text": [
"HePTP"
],
"offsets": [
[
743,
748
]
],
"normalized": []
},
{
"id": "PMID-10206983_T8",
"type": "Protein",
"text": [
"Erk1"
],
"offsets": [
[
810,
814
]
],
"normalized": []
},
{
"id": "PMID-10206983_T9",
"type": "Protein",
"text": [
"2"
],
"offsets": [
[
819,
820
]
],
"normalized": []
},
{
"id": "PMID-10206983_T10",
"type": "Protein",
"text": [
"HePTP"
],
"offsets": [
[
935,
940
]
],
"normalized": []
},
{
"id": "PMID-10206983_T11",
"type": "Protein",
"text": [
"HePTP"
],
"offsets": [
[
1044,
1049
]
],
"normalized": []
},
{
"id": "PMID-10206983_T12",
"type": "Protein",
"text": [
"HePTP"
],
"offsets": [
[
1212,
1217
]
],
"normalized": []
},
{
"id": "PMID-10206983_T13",
"type": "Entity",
"text": [
"tyrosine"
],
"offsets": [
[
216,
224
]
],
"normalized": []
},
{
"id": "PMID-10206983_T14",
"type": "Entity",
"text": [
"tyrosine"
],
"offsets": [
[
245,
253
]
],
"normalized": []
},
{
"id": "PMID-10206983_T15",
"type": "Entity",
"text": [
"T cell antigen receptor"
],
"offsets": [
[
512,
535
]
],
"normalized": []
},
{
"id": "PMID-10206983_T16",
"type": "Entity",
"text": [
"5' promoter"
],
"offsets": [
[
595,
606
]
],
"normalized": []
},
{
"id": "PMID-10206983_T17",
"type": "Entity",
"text": [
"N terminus"
],
"offsets": [
[
1116,
1126
]
],
"normalized": []
}
] | [] | [
{
"id": "PMID-10206983_1",
"entity_ids": [
"PMID-10206983_T1",
"PMID-10206983_T2"
]
},
{
"id": "PMID-10206983_2",
"entity_ids": [
"PMID-10206983_T3",
"PMID-10206983_T4"
]
}
] | [
{
"id": "PMID-10206983_R1",
"type": "Protein-Component",
"arg1_id": "PMID-10206983_T5",
"arg2_id": "PMID-10206983_T16",
"normalized": []
}
] |
194 | PMID-10233875 | [
{
"id": "PMID-10233875__text",
"type": "abstract",
"text": [
"NF-kappaB activation is required for C5a-induced interleukin-8 gene expression in mononuclear cells. \nC5a, a potent peptide chemoattractant, stimulates interleukin-8 (IL-8) secretion from peripheral blood mononuclear cells (PBMC). Experiments were conducted to understand the mechanisms for C5a-induced IL-8 production, which was 14-fold greater than that in unstimulated cells by 2 hours. IL-8 secretion was accompanied by accumulation of IL-8 mRNA in the cytosol and by nuclear expression of a kappaB DNA binding activity within 30 minutes. AP-1 but not NF-IL-6 DNA binding activity was also detected in C5a-stimulated PBMC; however, its delayed expression (maximal at 4 hours) suggested a less important role in the rapid production of IL-8. The correlation between C5a-induced kappaB binding activity and IL-8 gene expression was examined in the RAW264.7 macrophage cells using reporter genes directed by the kappaB sequence from IkappaBalpha and IL-8 promoter regions. C5a-induced reporter gene expression was abolished by introducing mutations into the kappaB sites and by coexpression of a dominant negative IkappaBalpha construct resistant to agonist-induced phosphorylation. Pertussis toxin, which ADP-ribosylates the Gi proteins known to couple to the C5a receptor, produced minimal inhibition of C5a-induced IL-8 expression and had little effect on C5a-induced calcium mobilization in RAW264.7 cells. These results suggest that NF-kappaB activation is required for C5a-induced IL-8 gene expression and that this response is mediated primarily through a pertussis toxin-insensitive pathway.\n"
],
"offsets": [
[
0,
1601
]
]
}
] | [
{
"id": "PMID-10233875_T1",
"type": "Protein",
"text": [
"interleukin-8"
],
"offsets": [
[
49,
62
]
],
"normalized": []
},
{
"id": "PMID-10233875_T2",
"type": "Protein",
"text": [
"interleukin-8"
],
"offsets": [
[
152,
165
]
],
"normalized": []
},
{
"id": "PMID-10233875_T3",
"type": "Protein",
"text": [
"IL-8"
],
"offsets": [
[
167,
171
]
],
"normalized": []
},
{
"id": "PMID-10233875_T4",
"type": "Protein",
"text": [
"IL-8"
],
"offsets": [
[
303,
307
]
],
"normalized": []
},
{
"id": "PMID-10233875_T5",
"type": "Protein",
"text": [
"IL-8"
],
"offsets": [
[
390,
394
]
],
"normalized": []
},
{
"id": "PMID-10233875_T6",
"type": "Protein",
"text": [
"IL-8"
],
"offsets": [
[
440,
444
]
],
"normalized": []
},
{
"id": "PMID-10233875_T7",
"type": "Protein",
"text": [
"NF-IL-6"
],
"offsets": [
[
556,
563
]
],
"normalized": []
},
{
"id": "PMID-10233875_T8",
"type": "Protein",
"text": [
"IL-8"
],
"offsets": [
[
739,
743
]
],
"normalized": []
},
{
"id": "PMID-10233875_T9",
"type": "Protein",
"text": [
"IL-8"
],
"offsets": [
[
809,
813
]
],
"normalized": []
},
{
"id": "PMID-10233875_T10",
"type": "Protein",
"text": [
"IkappaBalpha"
],
"offsets": [
[
934,
946
]
],
"normalized": []
},
{
"id": "PMID-10233875_T11",
"type": "Protein",
"text": [
"IL-8"
],
"offsets": [
[
951,
955
]
],
"normalized": []
},
{
"id": "PMID-10233875_T12",
"type": "Protein",
"text": [
"IkappaBalpha"
],
"offsets": [
[
1115,
1127
]
],
"normalized": []
},
{
"id": "PMID-10233875_T13",
"type": "Protein",
"text": [
"C5a receptor"
],
"offsets": [
[
1262,
1274
]
],
"normalized": []
},
{
"id": "PMID-10233875_T14",
"type": "Protein",
"text": [
"IL-8"
],
"offsets": [
[
1319,
1323
]
],
"normalized": []
},
{
"id": "PMID-10233875_T15",
"type": "Protein",
"text": [
"IL-8"
],
"offsets": [
[
1488,
1492
]
],
"normalized": []
},
{
"id": "PMID-10233875_T16",
"type": "Entity",
"text": [
"NF-kappaB"
],
"offsets": [
[
0,
9
]
],
"normalized": []
},
{
"id": "PMID-10233875_T17",
"type": "Entity",
"text": [
"C5a"
],
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[
37,
40
]
],
"normalized": []
},
{
"id": "PMID-10233875_T18",
"type": "Entity",
"text": [
"C5a"
],
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[
102,
105
]
],
"normalized": []
},
{
"id": "PMID-10233875_T19",
"type": "Entity",
"text": [
"C5a"
],
"offsets": [
[
291,
294
]
],
"normalized": []
},
{
"id": "PMID-10233875_T20",
"type": "Entity",
"text": [
"kappaB"
],
"offsets": [
[
496,
502
]
],
"normalized": []
},
{
"id": "PMID-10233875_T21",
"type": "Entity",
"text": [
"AP-1"
],
"offsets": [
[
543,
547
]
],
"normalized": []
},
{
"id": "PMID-10233875_T22",
"type": "Entity",
"text": [
"DNA"
],
"offsets": [
[
564,
567
]
],
"normalized": []
},
{
"id": "PMID-10233875_T23",
"type": "Entity",
"text": [
"C5a"
],
"offsets": [
[
606,
609
]
],
"normalized": []
},
{
"id": "PMID-10233875_T24",
"type": "Entity",
"text": [
"C5a"
],
"offsets": [
[
769,
772
]
],
"normalized": []
},
{
"id": "PMID-10233875_T25",
"type": "Entity",
"text": [
"kappaB"
],
"offsets": [
[
781,
787
]
],
"normalized": []
},
{
"id": "PMID-10233875_T26",
"type": "Entity",
"text": [
"kappaB sequence"
],
"offsets": [
[
913,
928
]
],
"normalized": []
},
{
"id": "PMID-10233875_T27",
"type": "Entity",
"text": [
"promoter regions"
],
"offsets": [
[
956,
972
]
],
"normalized": []
},
{
"id": "PMID-10233875_T28",
"type": "Entity",
"text": [
"C5a"
],
"offsets": [
[
974,
977
]
],
"normalized": []
},
{
"id": "PMID-10233875_T29",
"type": "Entity",
"text": [
"reporter gene"
],
"offsets": [
[
986,
999
]
],
"normalized": []
},
{
"id": "PMID-10233875_T30",
"type": "Entity",
"text": [
"kappaB sites"
],
"offsets": [
[
1059,
1071
]
],
"normalized": []
},
{
"id": "PMID-10233875_T31",
"type": "Entity",
"text": [
"ADP"
],
"offsets": [
[
1207,
1210
]
],
"normalized": []
},
{
"id": "PMID-10233875_T32",
"type": "Entity",
"text": [
"C5a"
],
"offsets": [
[
1307,
1310
]
],
"normalized": []
},
{
"id": "PMID-10233875_T33",
"type": "Entity",
"text": [
"C5a"
],
"offsets": [
[
1360,
1363
]
],
"normalized": []
},
{
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195 | PMID-1851743 | [
{
"id": "PMID-1851743__text",
"type": "abstract",
"text": [
"Inhibition of protein phosphatases by okadaic acid induces AP1 in human T cells. \nTo examine the role of protein phosphatases in T cell activation, Jurkat cells were treated with okadaic acid, an inhibitor of type 1 and 2A phosphatases, and nuclear extracts were examined for the presence of AP1 as a measure of early T cell activation. Okadaic acid was found to be a potent inducer of AP1. In contrast to phorbol esters such as phorbol myristate acetate (PMA), the induction of AP1 by okadaic acid occurs predominantly by transcriptional activation of the jun and fos family of proto-oncogenes. Surprisingly, while the addition of phytohemagglutinin further enhanced the induction of AP1, the addition of PMA inhibited it. Okadaic acid treatment was found to dramatically increase mRNA transcripts of the jun family of proto-oncogenes including c-jun, junD, and junB and to a lesser extent the fos family including c-fos and fra-1. By comparison, PMA is a very inefficient inducer of the jun gene family in Jurkat cells. Similar to its effect on the induction of AP1 by okadaic acid, PMA inhibits the induction of c-jun mRNA by okadaic acid. Transfection of c-jun promoter constructs confirmed the marked difference between PMA and okadaic acid in inducing c-jun transcription. The induction of AP1 by okadaic acid suggests that protein phosphatases 1 and 2A (PP1 and PP2A) may be involved in T cell activation as important negative regulators of the transcription factor AP1.\n"
],
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] | [] | [] | [] |
196 | PMID-8631821 | [
{
"id": "PMID-8631821__text",
"type": "abstract",
"text": [
"Structural and functional characterization of the human CD36 gene promoter: identification of a proximal PEBP2/CBF site. \nCD36 is a cell surface glycoprotein composed of a single polypeptide chain, which interacts with thrombospondin, collagens type I and IV, oxidized low density lipoprotein, fatty acids, anionic phospholipids, and erythrocytes parasitized with Plasmodium falciparum. Its expression is restricted to a few cell types, including monocyte/macrophages. In these cells, CD36 is involved in phagocytosis of apoptotic cells, and foam cell formation by uptake of oxidized low density lipoprotein. To study the molecular mechanisms that control the transcription of the CD36 gene in monocytic cells we have isolated and analyzed the CD36 promoter. Transient expression experiments of 5'-deletion fragments of the CD36 promoter coupled to luciferase demonstrated that as few as 158 base pairs upstream from the transcription initiation site were sufficient to direct the monocyte-specific transcription of the reporter gene. Within the above region, the fragment spanning nucleotides -158 to -90 was required for optimal transcription in monocytic cells. Biochemical analysis of the region -158/-90 revealed a binding site for transcription factors of the polyomavirus enhancer-binding protein 2/core-binding factor (PEBP2/CBF) family at position -103. Disruption of the PEBP2/CBF site markedly diminished the role of the PEBP2/CBF factors in the constitutive transcription of the CD36 gene. The involvement of members of the PEBP2/CBF family in chromosome translocations associated with acute myeloid leukemia, and in the transcriptional regulation of the myeloid-specific genes encoding for myeloperoxidase, elastase, and the colony-stimulating factor receptor, highlights the relevance of the regulation of the CD36 gene promoter in monocytic cells by members of the PEBP2/CBF family.\n"
],
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[
0,
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]
}
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] |
197 | PMID-8634413 | [
{
"id": "PMID-8634413__text",
"type": "abstract",
"text": [
"STAT-related transcription factors are constitutively activated in peripheral blood cells from acute leukemia patients. \nA signal transduction pathway activated by many cytokines has recently been elaborated. The JAK kinases and the signal transducers and activators of transcription (STAT) factors have been found to be essential components. In this report, we describe the presence of constitutively activated STAT factors in peripheral blood cells from patients with acute leukemia. We used oligonucleotide probes from the beta-casein and IRF-1 gene promoters and the ISRE probe to detect STAT proteins in nuclear extracts from acute leukemia cells in bandshift assays. Specific DNA protein complex formation was observed with the probes from the beta-casein and IRF-1 gene promoters, but not with the ISRE oligonucleotide probe, when cell extracts from acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) were investigated. We used nonradioactive oligonucleotides as competitors to show the specificity of the complex formation. Specific antibodies directed against the individual STAT proteins were used in supershift experiments. STAT5- and STAT1-related factors were detected in ALL and STAT1-, STAT3-, and STAT5-related proteins were present in nuclear cell extracts from AML. Since the cells were not treated with cytokines before the nuclear proteins were extracted, we conclude that these factors are constitutively activated in vivo. It is likely that the constitutive activation of STAT proteins is a part of the events of leukemogenesis.\n"
],
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[
0,
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]
}
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"id": "PMID-8634413_T1",
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"id": "PMID-8634413_T13",
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772,
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805,
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}
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198 | PMID-9348104 | [
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"Helenalin, an anti-inflammatory sesquiterpene lactone from Arnica, selectively inhibits transcription factor NF-kappaB [see comments] \nAlcoholic extracts prepared form Arnicae flos, the collective name for flowerheads from Arnica montana and A. chamissonis ssp. foliosa, are used therapeutically as anti-inflammatory remedies. The active ingredients mediating the pharmacological effect are mainly sesquiterpene lactones, such as helenalin, 11alpha,13-dihydrohelenalin, chamissonolid and their ester derivatives. While these compounds affect various cellular processes, current data do not fully explain how sesquiterpene lactones exert their anti-inflammatory effect. We show here that helenalin, and, to a much lesser degree, 11alpha,13-dihydrohelenalin and chamissonolid, inhibit activation of transcription factor NF-kappaB. This difference in efficacy, which correlates with the compounds' anti-inflammatory potency in vivo, may be explained by differences in structure and conformation. NF-kappaB, which resides in an inactive, cytoplasmic complex in unstimulated cells, is activated by phosphorylation and degradation of its inhibitory subunit, IkappaB. Helenalin inhibits NF-kappaB activation in response to four different stimuli in T-cells, B-cells and epithelial cells and abrogates kappaB-driven gene expression. This inhibition is selective, as the activity of four other transcription factors, Oct-1, TBP, Sp1 and STAT 5 was not affected. We show that inhibition is not due to a direct modification of the active NF-kappaB heterodimer. Rather, helenalin modifies the NF-kappaB/IkappaB complex, preventing the release of IkappaB. These data suggest a molecular mechanism for the anti-inflammatory effect of sesquiterpene lactones, which differs from that of other nonsteroidal anti-inflammatory drugs (NSAIDs), indomethacin and acetyl salicylic acid.\n"
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199 | PMID-8039243 | [
{
"id": "PMID-8039243__text",
"type": "abstract",
"text": [
"Long-term inositol phosphate release, but not tyrosine kinase activity, correlates with IL-2 secretion and NF-AT induction in anti-CD3-activated peripheral human T lymphocytes. \nThe cascade of events within the first few minutes of T cell stimulation has been well characterized. Although many second messengers have been shown to be necessary and sufficient for T cell activation in a number of model systems, the rate-limiting step in peripheral T cells has not been demonstrated. To model effective versus ineffective CD3-mediated stimulation in peripheral T cells, we used two anti-CD3 mAbs that differ in their ability to stimulate purified T cells: OKT3, which causes early second messenger generation but is unable to activate T cells without a second signal, and 64.1, which stimulates T cell proliferation on its own. We found that tyrosine kinase activity was similar for both mAbs over a period of hours. However, the inositol phosphate response was stronger for 64.1 than for OKT3. To tie these events to gene activation, we measured NF-kappa B and NF-AT activity in the nucleus after anti-CD3 stimulation. Both stimuli induced the appearance of the NF-kappa B components (c-Rel, p65 (RelA), and p50 (NF-kappa B1)) and NF-kappa B DNA binding activity in the nucleus. However, only 64.1 induced NF-AT in the nucleus, correlating with its ability to activate T cells. Thus, NF-AT induction and IL-2 secretion were correlated with the levels of inositol phosphate release but not with gross levels of tyrosine kinase activity induced late following the response. On the other hand, NF-kappa B induction and IL-2 receptor expression occurred even with the smaller second messenger response generated by OKT3.\n"
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