| Background |
Core component of the DBIRD complex, a multiprotein complex that acts at the interface between core mRNP particles and RNA polymerase II (RNAPII) and integrates transcript elongation with the regulation of alternative splicing: the DBIRD complex affects local transcript elongation rates and alternative splicing of a large set of exons embedded in (A + T)-rich DNA regions. Inhibits SIRT1 deacetylase activity leading to increasing levels of p53/TP53 acetylation and p53-mediated apoptosis. Inhibits SUV39H1 methyltransferase activity. As part of a histone H3-specific methyltransferase complex may mediate ligand-dependent transcriptional activation by nuclear hormone receptors. Plays a critical role in maintaining genomic stability and cellular integrity following UV-induced genotoxic stress. Regulates the circadian expression of the core clock components NR1D1 and ARNTL/BMAL1. Enhances the transcriptional repressor activity of NR1D1 through stabilization of NR1D1 protein levels by preventing its ubiquitination and subsequent degradation (PubMed: 18235501, PubMed: 18235502, PubMed: 19131338, PubMed: 19218236, PubMed: 22446626, PubMed: 23352644, PubMed : 23398316). Represses the ligand-dependent transcriptional activation function of ESR2 (PubMed: 20074560). Acts as a regulator of PCK1 expression and gluconeogenesis by a mechanism that involves, at least in part, both NR1D1 and SIRT1 (PubMed: 24415752). Negatively regulates the deacetylase activity of HDAC3 and can alter its subcellular localization (PubMed: 21030595). Positively regulates the beta-catenin pathway (canonical Wnt signaling pathway) and is required for MCC-mediated repression of the beta-catenin pathway (PubMed: 24824780). Represses ligand-dependent transcriptional activation function of NR1H2 and NR1H3 and inhibits the interaction of SIRT1 with NR1H3 (PubMed: 25661920). Plays an important role in tumor suppression through p53/TP53 regulation; stabilizes p53/TP53 by affecting its interaction with ubiquitin ligase MDM2 (PubMed: 25732823). Represses the transcriptional activator activity of BRCA1 (PubMed: 20160719). Inhibits SIRT1 in a CHEK2 and PSEM3-dependent manner and inhibits the activity of CHEK2 in vitro (PubMed: 25361978). |
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