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

Nature. 1995 May 4;375(6526):78-81. doi: 10.1038/375078a0.


Fas is a type-I membrane protein that transduces an apoptotic signal. Binding of Fas ligand or agonistic anti-Fas antibody to Fas kills the cells by apoptosis. Studies in the nematode Caenorhabditis elegans have suggested that proteases such as interleukin-1 beta-converting enzyme (ICE) or the product of the C. elegans cell-death gene ced-3 are involved in apoptotic signal transduction. The activity of ICE can be inhibited by the product of crmA, a cytokine-response modifier gene encoded by cowpox virus. 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) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Surface / physiology*
  • Apoptosis / physiology*
  • Caspase 1
  • Cell Line
  • Cysteine Endopeptidases / physiology*
  • Humans
  • Mice
  • Molecular Sequence Data
  • Rats
  • Serpins / genetics
  • Serpins / physiology
  • Transformation, Genetic
  • Tumor Necrosis Factor-alpha / physiology
  • Viral Proteins*
  • fas Receptor


  • Antigens, Surface
  • Serpins
  • Tumor Necrosis Factor-alpha
  • Viral Proteins
  • fas Receptor
  • interleukin-1beta-converting enzyme inhibitor
  • Cysteine Endopeptidases
  • Caspase 1