Processing and activation of CMH-1 by granzyme B

Granzyme B plays an essential role in cytotoxic T lymphocyte (CTL)-mediated cell killing, Recent studies suggest that granzyme B may exert its effect by cleaving and activating CPP32, a member of the interleukin-1 beta-converting enzyme/Ced-3 family of cysteine proteases, We have examined the processing and activation of CMH-1, a close homologue of CPP32, by granzyme B in vitro, We have found that granzyme B specifically cleaves CMH-1 at Asp(198)-Ser(199) between the p20 and p12 and activates the cysteine protease, Cleavage between p20 and the prosequence of CMH-1 at Asp(23)-Ala(24) is autocatalytic and is not required for CMH-1 activity in vitro. The cleavage and activation of CMH-1 by granzyme B in vitro suggest that, in addition to CPP32, CMH-1 may also play a role in CTL-mediated cell killing.