title: Processing and activation of CMH-1 by granzyme B.
abstract: 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 Asp198-Ser199 between the p20 and p12 and activates the cysteine protease. Cleavage between p20 and the prosequence of CMH-1 at Asp23-Ala24 is autocatalytic and is not required for CMH-1 activity in vitro. The cleavage and activation of CMH-1 by granzyme B in vitro sugge st that, in addition to CPP32, CMH-1 may also play a role in CTL-mediated cell killing.
authors.affiliation: Vertex Pharmaceuticals Incorporated, Cambridge, Massachusetts 02139, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Gu
authors.forename: C
authors.initials: C
authors.lastname: Sarnecki
authors.forename: M A
authors.initials: MA
authors.lastname: Fleming
authors.forename: J A
authors.initials: JA
authors.lastname: Lippke
authors.forename: R C
authors.initials: RC
authors.lastname: Bleackley
authors.forename: M S
authors.initials: MS
authors.lastname: Su
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D053179:Caspase 7; D020169:Caspases; D002384:Catalysis; D016923:Cell Death / Q000276:immunology; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D018076:DNA, Complementary; D004789:Enzyme Activation; D053804:Granzymes; D006868:Hydrolysis; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D012697:Serine Endopeptidases / Q000378:metabolism*; D013379:Substrate Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D018076:DNA, Complementary; D053804:Granzymes; D012697:Serine Endopeptidases; D053179:Caspase 7; D020169:Caspases; D003546:Cysteine Endopeptidases