Cell Division Cycle And Apoptosis Regulator 2 (CCAR2)

DBC1, initially cloned from a region on chromosome 8p21 homozygously deleted in breast cancers, forms a stable complex with SIRT1. DBC1 directly interacted with SIRT1 and inhibited SIRT1 activity in vitro and in vivo. Downregulation of DBC1 expression potentiated SIRT1-dependent inhibition of apoptosis induced by genotoxic stress.DCB1-mediated repression of SIRT1 led to increasing levels of p53 acetylation and upregulation of p53-mediated function. In contrast, depletion of endogenous DBC1 by RNA interference (RNAi) stimulated SIRT1-mediated deacetylation of p53 and inhibited p53-dependent apoptosis. Notably, these effects could be reversed in cells by concomitant knockdown of endogenous SIRT1. The deduced protein contains 818 amino acids.