Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20226 (TATA-binding protein)
 1,297 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endotoxin-induced cytokine gene transcription in monocytes and macrophages is regulated in part by NF-kappaB. We have previously shown that the p38 mitogen-activated protein (MAP) kinase is necessary for endotoxin-induced cytokine gene transcription. Due to the fact that most cytokine promoter sequences have active NF-kappaB sites, we hypothesized that the p38 MAP kinase was necessary for NF-kappaB-dependent gene expression. We found that NF-kappaB-dependent gene expression was reduced to near control levels with either SB 203580 or a dominant-negative p38 MAP kinase expression vector. Inhibition of the p38 MAP kinase did not alter NF-kappaB activation at any level, but it significantly reduced the DNA binding of TATA-binding protein (TBP) to the TATA box. The dominant-negative p38 MAP kinase expression vector interfered with the direct interaction of native TFIID (TBP) with a co-transfected p65 fusion protein. Likewise, this dominant-negative plasmid also interfered with the direct interaction of a co-transfected TBP fusion protein with the native p65 subunit. The p38 kinase also phosphorylated TFIID (TBP) in vitro, and SB 203580 inhibited phosphorylation of TFIID (TBP) in vivo. Thus, the p38 MAP kinase regulates NF-kappaB-dependent gene transcription, in part, by modulating activation of TFIID (TBP).
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PMID:The p38 mitogen-activated protein kinase is required for NF-kappaB-dependent gene expression. The role of TATA-binding protein (TBP). 1052 78

NFATp is one member of a family of transcriptional activators that regulate the expression of cytokine genes. To study mechanisms of NFATp transcriptional activation, we established a reconstituted transcription system consisting of human components that is responsive to activation by full-length NFATp. The TATA-associated factor (TAF(II)) subunits of the TFIID complex were required for NFATp-mediated activation in this transcription system, since TATA-binding protein (TBP) alone was insufficient in supporting activated transcription. In vitro interaction assays revealed that human TAF(II)130 (hTAF(II)130) and its Drosophila melanogaster homolog dTAF(II)110 bound specifically and reproducibly to immobilized NFATp. Sequences contained in the C-terminal domain of NFATp (amino acids 688 to 921) were necessary and sufficient for hTAF(II)130 binding. A partial TFIID complex assembled from recombinant hTBP, hTAF(II)250, and hTAF(II)130 supported NFATp-activated transcription, demonstrating the ability of hTAF(II)130 to serve as a coactivator for NFATp in vitro. Overexpression of hTAF(II)130 in Cos-1 cells inhibited NFATp activation of a luciferase reporter. These studies demonstrate that hTAF(II)130 is a coactivator for NFATp and represent the first biochemical characterization of the mechanism of transcriptional activation by the NFAT family of activators.
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PMID:Human Taf(II)130 is a coactivator for NFATp. 1131 76

Chronic inflammation has been implicated as a cofactor in the development of several human cancers. Interleukin-1beta is a key pro-inflammatory cytokine. We have previously shown associations between polymorphisms at position -511 and -31 in the promoter of the IL1B gene and risk of non-small cell lung cancer. In this study we investigated the functional role of the -31 T/C SNP in the regulation of the IL1B gene. The -31 T/C polymorphism is located in the core promoter and may affect the binding of transcription factors and thereby promoter activity. We therefore established a promoter reporter assay to explore the impact of the promoter variants on the expression of the gene. In the present study, we show that expression from the T-variant of the promoter was higher (p<0.001) than from the C-variant, in A549 cells. Electrophoretic mobility shift assays revealed differential binding of proteins to a promoter fragment containing the SNP. Interestingly, a highly specific complex formed on the C-variant that was not present on the T-variant. Supershift experiments implicated binding of both the CCAAT-enhancer binding protein beta (C/EBPbeta, also called NF-IL6) transcription factor and the TATA-box binding protein (TBP) to the SNP region. Due to the high frequency of this SNP, differences in IL1B gene expression caused by the variants may have significant biological impact in the population.
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PMID:Differential binding of proteins to the IL1B -31 T/C polymorphism in lung epithelial cells. 1758 93