Involvement of an ICE-like protease in Fas-mediated apoptosis

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Abstract

FAS is a type-I membrane protein that transduces an apoptotic signal1,2. Binding of Fas ligand or agonistic anti-Fas antibody to Fas kills the cells by apoptosis3. Studies in the nematode Caenorhabditis elegans have suggested that proteases such as interleukin-Iβ-converting enzyme (ICE) or the product of the C. elegans cell-death gene ced-3 are involved in apoptotic signal transduction4. The activity of ICE can be inhibited by the product of crmA, a cytokine-response modifier gene encoded by cowpox virus5á€-7. 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)8,9 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.

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Enari, M., Hug, H. & Nagata, S. Involvement of an ICE-like protease in Fas-mediated apoptosis. Nature 375, 78–81 (1995) doi:10.1038/375078a0

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