title: Requirement of an ICE/CED-3 protease for Fas/APO-1-mediated apoptosis.
abstract: The Fas/APO-1 receptor is one of the major regulators of apoptosis. We report here that Fas/APO-1-mediated apoptosis requires the activation of a new class of cysteine proteases, including interleukin-1 beta-converting enzyme (ICE), 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.
authors.affiliation: Division of Immunochemistry, German Cancer Research Center, Heidelberg.
authors.forename: M
authors.initials: M
authors.lastname: Los
authors.forename: M
authors.initials: M
authors.lastname: Van de Craen
authors.forename: L C
authors.initials: LC
authors.lastname: Penning
authors.forename: H
authors.initials: H
authors.lastname: Schenk
authors.forename: M
authors.initials: M
authors.lastname: Westendorp
authors.forename: P A
authors.initials: PA
authors.lastname: Baeuerle
authors.forename: W
authors.initials: W
authors.lastname: Dröge
authors.forename: P H
authors.initials: PH
authors.lastname: Krammer
authors.forename: W
authors.initials: W
authors.lastname: Fiers
authors.forename: K
authors.initials: K
authors.lastname: Schulze-Osthoff
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D029742:Caenorhabditis elegans Proteins; D020170:Caspase 1; D020169:Caspases; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000502:physiology*; D016373:DNA, Antisense / Q000378:metabolism; D004789:Enzyme Activation; D015801:Helminth Proteins / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D015843:Serpins / Q000502:physiology; D014162:Transfection; D014764:Viral Proteins; D019014:fas Receptor
chemical_list: D000954:Antigens, Surface; D029742:Caenorhabditis elegans Proteins; D016373:DNA, Antisense; D015801:Helminth Proteins; D015843:Serpins; D014764:Viral Proteins; D019014:fas Receptor; C074641:interleukin-1beta-converting enzyme inhibitor; D020169:Caspases; D003546:Cysteine Endopeptidases; C089223:ced-3 protein, C elegans; D020170:Caspase 1