Cnidaria XIAP activates caspase-mediated cell death

In vertebrate, X-linked inhibitor of apoptosis (XIAP) is a potent inhibitor of apoptosis. XIAP inhibits apoptosis by interacting with proapoptotic caspases via the baculovirus IAP repeat (BIR) domains and mediating caspase ubiquitination via the really interesting new gene (RING) domain and ubiquitin-associated (UBA) domain. In invertebrate, mostly arthropods, XIAP is also known as an apoptosis inhibitor. To date, no study on basal metazoan XIAP has been documented. In the present work, we examined the biological activity of XIAP from jellyfish Aurelia coerulea (AcXIAP) and other non-bilaterians. AcXIAP possesses three BIRs and one RING domain but lacks the UBA domain. AcXIAP augmented the apoptosis-inducing activity of all of the four A. coerulea caspases, of both the initiator and the effector clades, identified in this study. AcXIAP activated caspase via one of the BIRs, which bound and stabilized the caspase, and the RING domain, which mediated ubiquitination on the p20 subunit of the caspase in a lysine-independent manner. Similar caspase-activating properties were also observed in the XIAP of hydra, coral, and sponge. In hydra, XIAP knockdown markedly decreased cell death induced by an apoptosis inducer. Together these results revealed the unconventional function and working mechanism of XIAP in Cnidaria, and shed new light into the functional and structural evolution of XIAP.