title: The Drosophila inhibitor of apoptosis D-IAP1 suppresses cell death induced by the caspase drICE.
abstract: Many members of the Inhibitor of Apoptosis (IAP) family inhibit cell death and existing data suggest at least two mechanisms of action. Drosophila IAPs (D-IAP1 and D-IAP2) and a baculovirus-derived IAP, Op-IAP, physically interact with and inhibit the anti-apoptotic activity of Reaper, HID, and Grim, three genetically defined inducers of apoptosis in Drosophila, while human IAPs, c-IAP1, c-IAP2, and X-IAP interact with a number of different proteins 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, Drosophila 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 caspases tested and physically interacted with the active, but not the proform of drICE. MIHA, the mouse homolog of X-IAP and an effective inhibitor of caspase-3, also interacted with and blocked apoptosis induced by active drICE but was relatively ineffective in blocking Sf-caspase-1. Op-IAP and D-IAP2 were unable to inhibit effectively any of the active caspases tested and failed to interact with drICE. The Drosophila IAPs and Op-IAP, but not MIHA, blocked HID-initiated activation of pro-drICE. We conclude that D-IAP1 is capable 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 more limited in their inhibitory targets and may be limited to inhibiting the activation of caspases.
authors.affiliation: Department of Entomology, The University of Georgia, Athens 30602, USA.
authors.forename: W J
authors.initials: WJ
authors.lastname: Kaiser
authors.forename: D
authors.initials: D
authors.lastname: Vucic
authors.forename: L K
authors.initials: LK
authors.lastname: Miller
mesh_terms: D000818:Animals; D017209:Apoptosis; D016367:Baculoviridae; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D029721:Drosophila Proteins; D004331:Drosophila melanogaster; D004789:Enzyme Activation; D051034:Inhibitor of Apoptosis Proteins; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D018411:Spodoptera; D014162:Transfection; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D051636:X-Linked Inhibitor of Apoptosis Protein
chemical_list: C111891:DIAP1 protein, Drosophila; C111892:DIAP2 protein, Drosophila; D029721:Drosophila Proteins; C108880:HID protein, Drosophila; D051034:Inhibitor of Apoptosis Proteins; D019476:Insect Proteins; D009479:Neuropeptides; D011498:Protein Precursors; D011506:Proteins; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; D051636:X-Linked Inhibitor of Apoptosis Protein; C086430:inhibitor of apoptosis, Nucleopolyhedrovirus; D020169:Caspases; C109171:drICE protein, Drosophila