CLONING AND EXPRESSION OF APOPTOSIS INHIBITORY PROTEIN HOMOLOGS THAT FUNCTION TO INHIBIT APOPTOSIS AND OR BIND TUMOR-NECROSIS-FACTOR RECEPTOR-ASSOCIATED FACTORS/

Baculovirus inhibitors of apoptosis (IAPs) act in insect cells to prev ent cell death, Here we describe three mammalian homologs of IAP, MIHA , MIHB, and MIHC, and a Drosophila IAP homolog, DIHA. Each protein bea rs three baculovirus IAP repeats and an N-terminal ring finger motif. Apoptosis mediated by interleukin 1 beta converting enzyme (ICE), whic h can be inhibited by Orgyia pseudotsugata nuclear polyhedrosis virus IAP (OpIAP) and compos virus crmA, was also inhibited by MIHA and MIHB . As MIHB and MIHC were able to bind to the tumor necrosis factor rece ptor-associated factors TRAF1 and TRAF2 in yeast two-hybrid assays, th ese results suggest that IAP proteins that inhibit apoptosis may do so by regulating signals required for activation of ICE-like proteases.