Involvement of CPP32/Yama(-like) proteases in Fas-mediated apoptosis.
Fas (Apo-1/CD95) belongs to the tumor necrosis factor/nerve growth factor receptor family and transmits apoptotic signals by binding to its ligand. Interleukin-1beta-converting enzyme (ICE), which shows substantial homology to the product of the cell death gene, ced-3, of Caenorhabditis elegans, is reported to be involved in Fas-mediated apoptosis. Using two human carcinoma-derived cell lines with undetectable levels of ICE, we found that an agonistic antihuman Fas antibody induces the activation of CPP32/Yama(-like) proteases that are ICE(-like) protease family members, and that a tetrapeptide inhibitor of CPP32/Yama protease, DEVD-CHO, inhibits the Fas-mediated activation of the proteases, Fas-mediated apoptosis, and CPP32/Yama(-like) proteolytic activities in vitro. Fas-mediated apoptosis is inhibited by the CPP32/Yama inhibitor DEVD-CHO, but not by the ICE inhibitor YVAD-CHO, suggesting a dominant role for the CPP32/Yama(-like) proteases and not ICE itself in Fas-mediated apoptosis of the human carcinoma cell lines.
Hasegawa
J
J
First Department of Surgery, Osaka University Medical School, Japan.
Kamada
S
S
Kamiike
W
W
Shimizu
S
S
Imazu
T
T
Matsuda
H
H
Tsujimoto
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015152:Blotting, Northern; D017173:Caenorhabditis elegans / Q000235:genetics; D006528:Carcinoma, Hepatocellular; D020170:Caspase 1; D053148:Caspase 3; D020169:Caspases; D016923:Cell Death / Q000235:genetics; D003546:Cysteine Endopeptidases / Q000096:biosynthesis / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004792:Enzyme Precursors / Q000096:biosynthesis / Q000378:metabolism; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D008113:Liver Neoplasms; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D014162:Transfection; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000502:physiology*
D004791:Enzyme Inhibitors; D004792:Enzyme Precursors; D009842:Oligopeptides; D011994:Recombinant Proteins; D019014:fas Receptor; C096429:L 709049; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases; D020170:Caspase 1