Caspase-3 can be pseudo-activated by a Ca2+-dependent proteolysis at a non-canonical site.
We have shown previously that calcium could trigger nuclear fragmentation, which was associated with a caspase 3 (C3)-like activity [Juin, P., Pelletier, M., Oliver, L., Tremblais, K., Gregoire, M., Meflah, K. and Vallette, F.M. (1998) Induction of a caspase-3-like activity by calcium in normal cytosolic extracts triggers nuclear apoptosis in a cell-free system. J. Biol. Chem. 273, 17559]. Here, we report that this activation is associated with a non-canonical truncation of C3, which induces a weak DEVDase activity. The cleavage of C3 via calcium-dependent proteolysis is independent of caspase 9; lysate exposure to calcium prevents further cleavage and activation by the cytochrome c and dATP pathway. Altogether, our data suggest that calcium could favour a necrotic mechanism by inducing the generation of a form of C3 insensitive to mitochondrial activation.
Pelletier
Maude
M
UMR 601 INSERM/Université de Nantes (Equipe 4), IFR 26, Nantes Cedex, France.
Oliver
Lisa
L
Meflah
Khaled
K
Vallette
François M
FM
D017209:Apoptosis; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D053148:Caspase 3; D020169:Caspases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002457:Cell Extracts / Q000737:chemistry; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D003838:Deoxyadenine Nucleotides / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D009154:Mutation / Q000235:genetics; D010447:Peptide Hydrolases / Q000378:metabolism; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D002457:Cell Extracts; D003838:Deoxyadenine Nucleotides; D021122:Protein Subunits; D045304:Cytochromes c; D010447:Peptide Hydrolases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; C108711:DEVDase; C026600:2'-deoxyadenosine triphosphate; D002118:Calcium