In vitro activation of CPP32 and Mch3 by Mch4, a novel human apoptotic cysteine protease containing two FADD-like domains.

摘要: Emerging evidence suggests that an amplifiable protease cascade consisting of multiple aspartate specific cysteine proteases (ASCPs) is responsible for the apoptotic changes observed in mammalian cells undergoing programmed cell death. Here we describe cloning two novel ASCPs from human Jurkat T-lymphocytes. Like other ASCPs, new proteases, named Mch4 and Mch5, are derived single chain proenzymes. However, their putative active sites contain a QACQG pentapeptide instead QACRG present ail known ASCPs. Also, N termini FADD-like death effector domains, suggesting possible interaction with FADD. Expression Escherichia coli produced that, like was potently inhibited (Kj = 14 nM) by tetrapeptide aldehyde DEVD-CHO. Interestingly, both serine granzyme B cleave recombinant proCPP32 proMch3 at conserved IXXD-S sequence to produce large small subunits proteases. Granzyme also cleaves proMch4 homologous IXXD-A processing mature Mch4. These observations suggest CPP32 Mch3 targets cells. The presence domains Mch5 role these Fas-apoptotic pathway. In addition, could participate pathways.