THE CED-3 ICE-LIKE PROTEASE MCH2 IS ACTIVATED DURING APOPTOSIS AND CLEAVES THE DEATH SUBSTRATE LAMIN-A/

Phylogenetic analysis of the CED-3/ICE family of cysteine proteases su ggests the existence of a subfamily most related to the Caenorhabditis elegans death gene ced-3 and includes Yama (CPP32, apopain), LAPS (Mc h3, CMH1), and Mch2. Here, we show that Mch2 is processed from its zym ogen form to a proteolytically active dimeric species during execution of the apoptotic program and by the cytotoxic T cell death protease g ranzyme B. Additionally, like Yama and LAP3, Mch2 functions downstream of the death inhibitors Bcl-2, Bcl-(xL), and CrmA. Importantly, Mch2, but not Yama or LAPS, is capable of cleaving lamin A to its signature apoptotic fragment, indicating that Mch2 is an apoptotic laminase.