Expression of bbc3, a pro-apoptotic BH3-only gene, is regulated by diversecell death and survival signals

BH3-only proteins function at a proximal point in a conserved cell death pa thway by binding, through their BH3 domains, to other Bcl-2 family members and triggering mitochondrial events associated with apoptosis. Here, we des cribe a strongly pro-apoptotic BH3-only protein, designated Bbc3, whose exp ression increases in response to diverse apoptotic stimuli. bbc3 mRNA level s were induced by exposure to DNA-damaging agents and by wild-type p53, whi ch mediates DNA damage-induced apoptosis. p53 transactivated bbc3 through c onsensus p53 binding sites within the bbc3 promoter region, indicating that bbc3 is a direct target of p53. Additionally, bbc3 mRNA was induced by p53 -independent apoptotic stimuli, including dexamethasone treatment of thymoc ytes, and serum deprivation of tumor cells. Insulin-like growth factor-1 an d epidermal growth factor, growth factors with broad anti-apoptotic activit y, were each sufficient to suppress Bbc3 expression in serum-starved tumor cells. These results suggest that the transcriptional regulation of bbc3 co ntributes to the transduction of diverse cell death and survival signals.