Involvement of an ICE-like protease in Fas-mediated apoptosis.
Fas is a type-I membrane protein that transduces an apoptotic signal. Binding of Fas ligand or agonistic anti-Fas antibody to Fas kills the cells by apoptosis. Studies in the nematode Caenorhabditis elegans have suggested that proteases such as interleukin-1 beta-converting enzyme (ICE) or the product of the C. elegans cell-death gene ced-3 are involved in apoptotic signal transduction. The activity of ICE can be inhibited by the product of crmA, a cytokine-response modifier gene encoded by cowpox virus. We report here that expression of crmA inhibits cytotoxicity induced by anti-Fas antibody or tumour necrosis factor (TNF). We have found a specific ICE inhibitor tetrapeptide (acetyl-Tyr-Val-Ala-Asp-chloromethylketone) that also prevents apoptosis induced by anti-Fas antibody. These results suggest an involvement of an ICE-like protease in Fas-mediated apoptosis and TNF-induced cytotoxicity.
Enari
M
M
Osaka Bioscience Institute, Japan.
Hug
H
H
Nagata
S
S
D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology*; D020170:Caspase 1; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000502:physiology*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D051381:Rats; D015843:Serpins / Q000235:genetics / Q000502:physiology; D014170:Transformation, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D014764:Viral Proteins; D019014:fas Receptor
D000954:Antigens, Surface; D015843:Serpins; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins; D019014:fas Receptor; C074641:interleukin-1beta-converting enzyme inhibitor; D003546:Cysteine Endopeptidases; D020170:Caspase 1