SMAC/Diablo Proteins and Enzymes

SMAC (second mitochondria-derived activator of caspase)/Diablo, the mammalian functional homologue of Drosophila Hid, Grim, and Reaper, regulates apoptosis by neutralizing inhibitor of apoptosis (IAP) proteins. IAP family members contain one to three baculovirus IAP repeat (BIR) domains, each exhibiting distinct functions and caspase specificity. The BIR2 domain inhibits caspase-3 and –7, whereas the BIR3 domain inhibits caspase-9 activity. SMAC/Diablo interacts with BIR2 and BIR3 domains of IAPs, thereby neutralizing IAP inhibition and promoting caspase catalytic activity and apoptosis.