Cloning and expression of apoptosis inhibitory protein homologs that function to inhibit apoptosis and/or bind tumor necrosis factor receptor-associated factors.

TLDR

Baculovirus inhibitors of apoptosis (IAPs) prevent cell death in insect cells and contain three baculovirus IAP repeats plus an N‑terminal ring finger motif. The study aims to characterize three mammalian IAP homologs (MIHA, MIHB, MIHC) and a Drosophila homolog (DIHA). The authors identified and characterized these homologs through sequence analysis and structural comparison. MIHA and MIHB inhibit ICE‑mediated apoptosis, and MIHB and MIHC bind TRAF1/2, suggesting that IAPs suppress apoptosis by modulating TRAF‑dependent ICE activation.

Abstract

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