Inhibitors of apoptosis proteins (IAPs) were originally identified in baculoviruses where they prevent apoptosis of the host cell, thereby allowing viral propagation. 1 Cellular homologues of the viral IAP have been identified in yeast and metazoans. IAPs share a conserved structure known as the baculovirus IAP repeat (BIR) domain, which is an B80 amino acid zincfinger motif. These proteins include DIAP1 and DIAP2 in Drosophila, XIAP, cIAP1, cIAP2 and ML-IAP as well as the more distantly related family members NAIPs, Survivin and BRUCE in vertebrates. 2 Some IAP proteins can act as potent inhibitors of apoptosis and appear to be the only endogenous inhibitors that directly inhibit both initiator and effector caspases.

The most extensively studied IAP is X-linked inhibitor of apoptosis protein (XIAP). 3 This protein comprises three BIR domains at its N-terminus and a RING domain that has E3 ubiquitin ligase activity at its C-terminus. Cells transfected with XIAP are protected from apoptosis in response to a range of stimuli. XIAP directly binds to and inhibits caspases 3, 7 and 9. Although XIAP is ubiquitously expressed, XIAP-deficient mice were not reported to have any gross phenotypic abnormalities or any profound defects in programmed cell death following the induction of apoptosis by a variety of stimuli. 4 Recently, however, XIAP-deficient sympathetic neurons were reported to be more susceptible to cytochrome c-induced cell death. 5