Requirement of an ICE/CED-3 protease for Fas/APO-1-mediated apoptosis
M Los, MV Craen, LC Penning, H Schenk… - Nature, 1995 - nature.com
M Los, MV Craen, LC Penning, H Schenk, M Westendorp, PA Baeuerle, W Dröge…
Nature, 1995•nature.comTHE 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 …
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 …
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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