Phospho-DBC1 (Thr454) Antibody - #AF4482

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. Represses the ligand-dependent transcriptional activation function of ESR2. Acts as a regulator of PCK1 expression and gluconeogenesis by a mechanism that involves, at least in part, both NR1D1 and SIRT1. Negatively regulates the deacetylase activity of HDAC3 and can alter its subcellular localization. Positively regulates the beta-catenin pathway (canonical Wnt signaling pathway) and is required for MCC-mediated repression of the beta-catenin pathway. Represses ligand-dependent transcriptional activation function of NR1H2 and NR1H3 and inhibits the interaction of SIRT1 with NR1H3. Plays an important role in tumor suppression through p53/TP53 regulation; stabilizes p53/TP53 by affecting its interaction with ubiquitin ligase MDM2. Represses the transcriptional activator activity of BRCA1. Inhibits SIRT1 in a CHEK2 and PSEM3-dependent manner and inhibits the activity of CHEK2 in vitro.

ATM/ATR-mediated phosphorylation at Thr-454 upon DNA damage promotes binding to SIRT1. Phosphorylation at Thr-454 promotes its sumoylation by switching the binding partner of CCAR2 from SENP1 to PIAS3.

Acetylation at Lys-112 and Lys-215 by KAT8 prevents inhibitory binding to SIRT1 and increases its deacetylase activity.

Genotoxic stress induces its sumoylation and sumoylation promotes the SIRT1-CCAR2 interaction which in turn inhibits SIRT1-mediated deacetylation of p53/TP53. Sumoylation leads to transcriptional activation of p53/TP53 by sequestering SIRT1 from p53/TP53. Desumoylated by SENP1.

Nucleus. Cytoplasm.
Note: Recruited to chromatin, post-UV irradiation. Sequestered to the cytoplasm in the presence of MCC. Translocated to the cytoplasm during UV-induced apoptosis.

Expressed in gastric carcinoma tissue and the expression gradually increases with the progression of the carcinoma (at protein level). Expressed ubiquitously in normal tissues. Expressed in 84 to 100% of neoplastic breast, lung, and colon tissues.

Component of the DBIRD complex. Interacts with ZNF326/ZIRD; the interaction is direct. Interacts (via N-terminus) with SIRT1, which inhibits the deacetylation of substrates. Interacts (via N-terminus) with SUV39H1; this interaction abolishes the interaction with SIRT1. Part of a complex composed at least of ASCL2, EMSY, HCFC1, HSPA8, CCAR2, MATR3, MKI67, RBBP5, TUBB2A, WDR5 and ZNF335; this complex may have a histone H3-specific methyltransferase activity. Interacts with NR1D1. Interacts (via N-terminus) with ESR1 and ESR2. Interacts (via N-terminus) with HDAC3 (via C-terminus). Interacts with HDAC1 and MED2F. Interacts with MCC. Interacts (via N-terminus) with NR1H2 and NR1H3 in a ligand-independent manner. Interacts with CSNK2A1. Interacts (via N-terminus) with p53/TP53. Interacts (via N-terminus) with BRCA1 (via the BRCT domains). Interacts (via N-terminus) with CHEK2 (via protein kinase domain). Interacts with PSEM3. Interacts (via N-terminus) with PSIA3 and SENP1. The sumoylated form shows a preferential interaction with SIRT1 as compared to its unmodified form.