IDENTIFICATION AND CHARACTERIZATION OF CPP32 2MCH2 HOMOLOG-1, A NOVELCYSTEINE PROTEASE SIMILAR TO CPP32/

We have identified and characterized a novel cysteine protease named C MH-1 that is a new member of the interleukin 1 beta converting enzyme (ICE) family of proteases with substrate specificity for Asp-X. CMH-1 has the highest similarity to CPP32 (52% amino acid identity) and MCH2 (31% identical). CMH-1 shares conserved amino acid residues that form the core structure of ICE as well as those residues involved in catal ysis and in the P1 aspartate binding. Overexpression of CMH-1 in COS c ells resulted in the processing of CMH-1 and the induction of apoptosi s of transfected cells. Coexpression of CMH-1 with poly(ADP-ribose) po lymerase (PARP) also resulted in a specific cleavage of PARP. Purified recombinant CMH-1 cleaved PARP but not interleukin 1 beta precursor i n vitro.