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

Abstract

FAS is a type-I membrane protein that transduces an apoptoticsignal1, 2. Binding of Fas ligand or agonistic anti-Fas antibody toFas kills the cells by apoptosis3. Studies in the nematode Caenor-hahditis elegans have suggested that proteases such as interleukin-lp-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, acytokine-response modifier gene encoded by cowpox virus5-7. Wereport here that expression of crmA inhibits cytotoxicity inducedby anti-Fas antibody or tumour necrosis factor (TNF). We havefound a specific ICE inhibitor tetrapeptide (acetyl-Tyr-Val-Ala-Asp-chloromethylketone)8, 9 that also prevents apoptosis inducedby anti-Fas antibody. These results suggest an involvement of anICE-Iike protease in Fas-mediated apoptosis and TNF-inducedcytotoxicity. © 1995, Nature Publishing Group. All Rights Reserved.