Caspase-3 and inhibitor of apoptosis protein(s) interactions in Saccharomyces cerevisiae and mammalian cells

Using a heterologous yeast expression assay, we show that inhibitor of apop tosis proteins (IAPs) suppress caspase-3-mediated cytotoxicity in the order of XIAP > c-IAP2 > cIAP2 > survivin. The same ordering of IAP activities w as demonstrated in mammalian cells expressing an auto-activating caspase-3, The relative anti-apoptotic activities of each IAP depended on the particu lar death stimulus, For IAP-expressing cells treated with camptothecin, sur vival correlated with their intrinsic anti-caspase-3 activity. However, c-I AP1-transfected cells were disproportionately resistant to tumor necrosis f actor-alpha, suggesting that its anti-apoptotic activities extend beyond ca spase-3 or -7 inhibition. Yeast-based caspase assays provide rapid, reliabl e information on specificity and activity of the IAPs and aid in identifyin g critical targets in mammalian apoptotic pathways. (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All righ ts reserved.