Cleavage of caspase family members by granzyme B: a comparative study in vitro.
The aspartase granzyme B is one of the major components of the granules involved in cell killing by cytotoxic T lymphocytes. Granzyme B has been shown to activate the apoptotic death pathway in the target cell, and this involves activation of members of the caspase (CASP) protein family. Therefore, activational cleavage of mouse (m) CASP proforms by granzyme B was examined in vitro. CASP can be subdivided in the CASP-1 (interleukin-1 beta-converting enzyme; ICE) subfamily, the CASP-2 (Ich1) subfamily, and the CASP-3 (CPP32) subfamily. Our results reveal that the proforms of the CASP-3 subfamily members mCASP-3 and mCASP-7 are hydrolyzed by granzyme B, while proforms of CASP-2 and CASP-1 subfamily members are not directly cleaved. Only one CASP-3 subfamily member, pro-mCASP-6, was not proteolytically cleaved by granzyme B. These results indicate that two members of the CASP-3 subfamily, but no others, become activated by granzyme B.
Van de Craen
M
M
Laboratory of Molecular Biology, Flanders Interuniversity Institute for Biotechnology and University of Ghent, Belgium.
Van den Brande
I
I
Declercq
W
W
Irmler
M
M
Beyaert
R
R
Tschopp
J
J
Fiers
W
W
Vandenabeele
P
P
D000818:Animals; D020170:Caspase 1; D053143:Caspase 2; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism; D004792:Enzyme Precursors / Q000235:genetics / Q000378:metabolism; D053804:Granzymes; D006868:Hydrolysis; D051379:Mice; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism*; D014158:Transcription, Genetic
D004792:Enzyme Precursors; D011506:Proteins; D053804:Granzymes; C509214:Gzmb protein, mouse; D012697:Serine Endopeptidases; C505409:Casp3 protein, mouse; D053143:Caspase 2; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases; D020170:Caspase 1