SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes

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R-HSA-111464
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Homo sapiens
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Second mitochondria derived activator of caspase/direct inhibitor of apoptosis binding protein with low pI (SMAC, also known as DIABLO) regulates XIAP function and potentiates caspase-3, -7 and -9 activity by disrupting the interaction of caspases with XIAP. Residues 56-59 of SMAC (DIABLO) are homologous to the amino-terminal motif that is used by caspase-9 (CASP9) to bind to the BIR3 domain of XIAP. SMAC (DIABLO) competes with CASP9 for binding to BIR3 domain of XIAP promoting the release of XIAP from the CASP9:apoptosome complex (Srinivasula SM et al. 2001; Salvesen et al. 2002). The binding of SMAC to the BIR2 and BIR3 regions of XIAP creates a steric hindrance that is essential for preventing binding of XIAP linker region with effector caspases CASP3 and CASP7 thus achieving neutralization of XIAP inhibition. The strong affinity for XIAP allows SMAC (DIABLO) to displace caspase-3, -7 from the XIAP:caspase complexes (Wu G et al. 2000; Chai J et al. 2001; Huang Y et al. 2003; Abhari BA & Davoodi J 2008).

Literature References
PubMed ID Title Journal Year
12042762 IAP proteins: blocking the road to death's door

Salvesen, GS, Duckett, CS

Nat Rev Mol Cell Biol 2002
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