Second mitochondria?derived activator of caspases protein (SMAC, also known as direct IAP binding protein with low pI or DIABLO) in its dimeric form interacts and antagonizes X?linked inhibitor of apoptosis protein (XIAP) by concurrently targeting both BIR2 and BIR3 domains of XIAP (Chai J et al. 2000; Liu Z et sl. 2000; Burke SP & Smith JB 2010). XIAP inhibits apoptosis by binding to and inhibiting the effectors caspase?3 and ?7 and an initiator caspase?9 (Deveraux QL et al. 1997; Paulsen M et al. 2008). During apoptosis, SMAC (DIABLO) is released from the mitochondria (Du C et al. 2000). In the cytosol, SMAC binds to XIAP displacing it from caspase:XIAP complexes liberating the active caspases (Wu G et al. 2000; Abhari BA & Davoodi J 2008).
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