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)

IL-1beta is produced primarily by activated monocytes/macrophages. We report in this study that IL-1beta induces the human pro-IL-1beta (IL1B) gene promoter in human THP-1 monocytic cells. The -131 to +12 minimal IL1B promoter was induced by IL-1beta in a dose-dependent manner. The promoter possesses two important transcription factor binding motifs, one for an ETS family transcription factor Spi-1 (PU.1), and the other a binding site for NF-IL6 (CCAAT/enhancer binding protein beta). Autocrine promoter activity was completely inhibited by mutation of the Spi-1 site. Mutation of the NF-IL6 binding motif caused partial loss of activity. EMSAs using THP-1 cell nuclear extracts indicated that IL-1beta significantly induced Spi-1 binding to its target site within the IL1B promoter that was maximal at 1 h after stimulation, correlating with the kinetics of IL-1beta induction. The importance of Spi-1 was supported by our observation that Spi-1-deficient EL4 thymocytes exhibited IL-1beta-induced activity only after transfection with a Spi-1 expression vector. Moreover, TNFR-associated factor 6 also required Spi-1 to activate the promoter. Transfection studies using Spi-1 mutant constructs showed that the TATA-binding protein binding and glutamine-rich domains of Spi-1 were important for IL-1beta induction, whereas LPS induction required the proline, glutamic acid, serine, and threonine-rich domain containing serine 148 as well as the TATA-binding protein and glutamine-rich domains. We conclude that the IL1B promoter is an IL-1beta-responsive sequence as a result of its ability to bind Spi-1 in response to IL-1beta.
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PMID:Autocrine induction of the human pro-IL-1beta gene promoter by IL-1beta in monocytes. 1182 35

Direct interaction of positive and negative regulators with the general transcription machinery modulates transcription. The TATA-binding protein (TBP) is one target for transcriptional regulators. In this study, we identified ZNF76 as a novel transcriptional repressor that targets TBP. ZNF76 interacts with TBP through both its N and C termini, and both regions are required for ZNF76 to exert its inhibitory function on p53-mediated transactivation. The inhibitory effect of ZNF76 on p53 activity was demonstrated by reporter assays and endogenous target gene expression. We mapped the TBP-interacting region in the C terminus of ZNF76 to a glutamic acid-rich domain, which acts in a dominant negative manner to enhance p53-mediated transactivation in reporter assays. Mutagenesis study for ZNF76 suggests a correlation between interaction with TBP and effect on p53-mediated transactivation, supporting the conclusion that ZNF76 targets TBP for transcriptional repression. Chromatin immunoprecipitation experiments suggest that ZNF76 prevents TBP from occupying the endogenous p21 promoter. ZNF76 is sumoylated by PIAS1 at lysine 411, which is in the minimal TBP-interacting region. Overexpression of PIAS1 and SUMO-1 abolishes the interaction between ZNF76 and TBP and partially relieves the repressive effect of ZNF76. These results suggest that ZNF76 functions as a transcriptional repressor through its interaction with TBP and that sumoylation modulates its transcriptional repression activity.
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PMID:ZNF76, a novel transcriptional repressor targeting TATA-binding protein, is modulated by sumoylation. 1528 Mar 58