BNIP3 alpha: A human homolog of mitochondrial proapoptotic protein BNIP3

Apoptosis is regulated by interaction of viral and cellular BCL-2 family an tiapoptotic proteins with various pro-apoptotic proteins, several of which are also members of the BCL-2 family. Cellular protein BNIP3 is a BCL-2 fam ily proapoptotic protein that interacts with viral antiapoptosis proteins s uch as adenoviruses E1B-19K and EBV-BHRF1 and cellular antiapoptosis protei ns such as BCL-2 and BCL-x(L). Database searches indicate that the human ge nome encodes an open reading frame for a protein, BNIP3 alpha, that shares substantial homology with BNIP3, The BNIP3 alpha open reading frame encodes a protein of 219 amino acids that contains a conserved BH3 domain and a CO OH-terminal trans-membrane domain, characteristic of several BCL-2 family p roapoptotic proteins. BNIP3a interacts with viral antiapoptosis protein E1B -19K and cellular antiapoptosis proteins BCL-2 and BCL-x(L). Overexpression of BNIP3 alpha in transfected cells results in apoptosis and suppresses th e antiapoptosis activity of E1B-19K and BCL-x(L). Like BNIP3, BNIP3 alpha s eems to be predominantly localized in mitochondria, These results suggest t hat BNIP3 alpha is a structural and functional homologue of BNIP3, BNIP3 an d BNIP3 alpha seem to be the first examples of homologues among the various human proapoptotic proteins. Northern blot analysis reveals that BNIP3a is expressed ubiquitously in most human tissues. In contrast, BNIP3 is expres sed well in several human tissues and less abundantly in certain tissues su ch as placenta and lung. These results suggest that although BNIP3 and BNIP 3 alpha may promote apoptosis simultaneously in most human tissues, BNIP3 a lpha may play a more universal role.