The Drosophila inhibitor of apoptosis D-IAP1 suppresses cell death inducedby the caspase drICE

Many members of the Inhibitor of Apoptosis (IAP) family inhibit cell death and existing data suggest at least two mechanisms of action. Drosophila IAP s (D-IAP1 and D-IAP2) and a baculovirus-derived IAP, Op-IAP, physically int eract with and inhibit the anti-apoptotic activity of Reaper, HID, and Grim , three genetically defined inducers of apoptosis in Drosophila, while huma n IAPs, c-IAP1, c-IAP2, and X-IAP interact with a number of different prote ins including specific members of the caspase family of cysteine proteases which are crucial in the execution of cell death. We have examined whether insect-active IAPs can inhibit apoptosis induced by selected caspases, Dros ophila drICE, Sf-caspase-1, and mammalian caspase-3, in insect SF-21 cells. D-IAP1 inhibited apoptosis induced by the active forms of all three caspas es tested and physically interacted with the active, but not the preform of drICE, MIHA, the mouse homolog of X-TAP and an effective inhibitor of casp ase-3, also interacted with and blocked apoptosis induced by active drICE b ut was relatively ineffective in blocking Sf-caspase-1. Op-IAP and D-IAP2 w ere unable to inhibit effectively any of the active caspases tested and fai led to interact with drICE. The Drosophila LAPS and Op-IAP, but not MIHA, b locked HID-initiated activation of pro-drTCE. We conclude that D-IAP1 is ca pable of inhibiting the activation of drICE as well as inhibiting apoptosis induced by the active form of drICE. In contrast, D-IAP2 and Op-IAP are mo re limited in their inhibitory targets and may be limited to inhibiting the activation of caspases, (C) 1998 Federation of European Biochemical Societ ies.