Activation of pro-caspase-7 by serine proteases includes a non-canonical specificity.
As a model to investigate the mechanism of caspase activation we have analysed the processing of pro-caspase-7 by serine proteases with varied specificities. The caspase-7 zymogen was rapidly activated by granzyme B and more slowly by subtilisin and cathepsin G, generating active enzymes with similar kinetic properties. Significantly, cathepsin G activated the zymogen by cleaving at a Gln-Ala bond, indicating that the canonical cleavage specificity at aspartic acid is not required for activation.
Zhou
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Program in Aging and Cell Death Research, The Burnham Institute, San Diego, CA 92037, USA.
Salvesen
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GS
D000595:Amino Acid Sequence; D053179:Caspase 7; D020169:Caspases; D056649:Cathepsin G; D002403:Cathepsins / Q000378:metabolism; D002918:Chymotrypsin / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000235:genetics / Q000378:metabolism*; D053804:Granzymes; D006801:Humans; D021382:Protein Sorting Signals / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism*; D013379:Substrate Specificity; D013381:Subtilisins / Q000378:metabolism; D014357:Trypsin / Q000378:metabolism
D018076:DNA, Complementary; D004792:Enzyme Precursors; D021382:Protein Sorting Signals; D011993:Recombinant Fusion Proteins; D002403:Cathepsins; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases; D013381:Subtilisins; D002918:Chymotrypsin; C534094:CTSG protein, human; D056649:Cathepsin G; D014357:Trypsin; C505520:CASP7 protein, human; D053179:Caspase 7; D020169:Caspases; D003546:Cysteine Endopeptidases