CCAR2
Description
The CCAR2 (cell cycle and apoptosis regulator 2) is a protein-coding gene located on chromosome 8.
CCAR2 is a human gene that encodes a protein involved in various cellular processes, including cell cycle regulation, apoptosis, and DNA repair. It is also implicated in tumor suppression and circadian rhythm regulation. The protein encoded by CCAR2 interacts with several other proteins, including SIRT1, p53/TP53, and BRCA1, and plays a role in mediating their functions.
CCAR2 is a key component of the DBIRD complex, a multi-protein group that bridges core mRNP particles with RNA polymerase II (RNAPII). This complex influences the rate of transcript elongation and regulates alternative splicing, particularly affecting exons located within (A+T)-rich DNA regions. CCAR2 also inhibits the deacetylase activity of SIRT1, leading to increased acetylation of p53/TP53, ultimately promoting p53-mediated apoptosis. Furthermore, it inhibits SUV39H1 methyltransferase activity. CCAR2 plays a crucial role in mediating ligand-dependent transcriptional activation by nuclear hormone receptors and is critical for maintaining genomic stability and cellular integrity after UV-induced DNA damage. It regulates the circadian expression of the core clock components NR1D1 and BMAL1, enhances the repressor activity of NR1D1 by stabilizing its protein levels, and represses the activation function of ESR2. CCAR2 also regulates PCK1 expression and gluconeogenesis, negatively regulates the deacetylase activity of HDAC3, and positively regulates the beta-catenin pathway. Additionally, it represses the activation function of NR1H2 and NR1H3, inhibits SIRT1 interaction with NR1H3, and contributes to tumor suppression through p53/TP53 regulation. CCAR2 stabilizes p53/TP53 by influencing its interaction with the ubiquitin ligase MDM2 and represses the activator activity of BRCA1. It inhibits SIRT1 in a CHEK2 and PSEM3-dependent manner and inhibits CHEK2 activity in vitro. {ECO:0000269|PubMed:18235501, ECO:0000269|PubMed:18235502, ECO:0000269|PubMed:19131338, ECO:0000269|PubMed:19218236, ECO:0000269|PubMed:20074560, ECO:0000269|PubMed:20160719, ECO:0000269|PubMed:21030595, ECO:0000269|PubMed:22446626, ECO:0000269|PubMed:23352644, ECO:0000269|PubMed:23398316, ECO:0000269|PubMed:24415752, ECO:0000269|PubMed:24824780, ECO:0000269|PubMed:25361978, ECO:0000269|PubMed:25661920, ECO:0000269|PubMed:25732823}
CCAR2 is also known as DBC-1, DBC1, KIAA1967, NET35, p30 DBC, p30DBC.
