Apoptosis, Caspase Activation Inhibitor (AVEN)

The AVEN gene encodes a 362-amino acid protein and is conserved in other mammalian species. Northern blot analysis detected a 1.7-kb AVEN transcript in all adult tissues tested, with highest expression in heart, skeletal muscle, kidney, liver, pancreas, and testis; a number of cell lines also expressed AVEN. Only those mutants of BCLXL that retained their antiapoptotic activity were capable of binding AVEN. AVEN was shown to interfere with the ability of APAF1 to self-associate, suggesting that AVEN impairs APAF1-mediated activation of caspases. Consistent with this idea, AVEN inhibited the proteolytic activation of caspases in a cell-free extract and suppressed apoptosis induced by APAF1 plus caspase-9 (CASP9). Thus, AVEN represents a novel class of cell death regulator.