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 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.
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Vertex Pharmaceuticals Incorporated, Cambridge, Massachusetts 02139, USA.
Sarnecki
C
C
Fleming
M A
MA
Lippke
J A
JA
Bleackley
R C
RC
Su
M S
MS
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
D018076:DNA, Complementary; D053804:Granzymes; D012697:Serine Endopeptidases; D053179:Caspase 7; D020169:Caspases; D003546:Cysteine Endopeptidases