BNIP3 (Bcl-2/E1B-19kDa interacting protein 3) is a pro-apoptotic mitochondrial protein and Bcl-2 family member that contains a Bcl-2 homology 3 (BH3) domain and a carboxyl terminal transmembrane (TM) domain. BNIP3 associates with anti-apoptotic family members Bcl-2, Bcl-xL, and the adenovirus homologue E1B-19kDa. BNIP3 is distinct from other Bcl-2 family members that contain only the BH3 domain in that the TM domain, and not the BH3 domain, is required for mitochondrial targeting and pro-apoptotic activity. Increased expression of BNIP3 under hypoxic conditions is mainly regulated by the transcription factor HIF-1α. Silencing of the BNIP3 promoter by methylation has been observed in several types of cancer cells and may play an important role in their survival.
