Requirement of an ICE/CED-3 protease for Fas/APO-1-mediated apoptosis

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Abstract

THE Fas/APO-1 receptor is one of the major regulators of apoptosis1á€-7. We report here that Fas/APO-1-mediated apoptosis requires the activation of a new class of cysteine proteases, including interleukin-lβ-converting enzyme (ICE)8á€-10, which are homologous to the product of the Caenorhabditis elegans cell-death gene ced-3 (refs 11, 12). Triggering of Fas/APO-1 rapidly stimulated the proteolytic activity of ICE. Overexpression of ICE, achieved by electroporation and microinjection, strongly potentiated Fas/ APO-1-mediated cell death. In addition, inhibition of ICE activity by protease inhibitors, as well as by transient expression of the pox virus-derived serpin inhibitor CrmA or an antisense ICE construct, substantially suppressed Fas/APO-1-triggered cell death. We conclude that activation of ICE or an ICE-related protease is a critical event in Fas/APO-1-mediated cell death.

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Los, M., Craen, M., Penning, L. et al. Requirement of an ICE/CED-3 protease for Fas/APO-1-mediated apoptosis. Nature 375, 81–83 (1995) doi:10.1038/375081a0

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