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08:47

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

M Enari1, H Hug, S Nagata

  • 1Osaka Bioscience Institute, Japan.

Nature
|May 4, 1995
PubMed

Insights

This study reveals that an interleukin-1 beta-converting enzyme (ICE)-like protease plays a crucial role in Fas-mediated apoptosis and tumor necrosis factor (TNF) cytotoxicity. Inhibiting this protease blocks cell death, highlighting its significance in these cellular processes.

Area of Science:

  • Cell biology
  • Molecular biology
  • Immunology

Background:

  • Fas is a type-I membrane protein that initiates apoptosis upon binding Fas ligand or agonistic anti-Fas antibody.
  • Studies in Caenorhabditis elegans suggest proteases like interleukin-1 beta-converting enzyme (ICE) and ced-3 are involved in apoptotic signaling.
  • Cowpox virus-encoded cytokine-response modifier A (crmA) inhibits ICE activity.

Purpose of the Study:

  • To investigate the role of ICE-like proteases in Fas-mediated apoptosis and TNF-induced cytotoxicity.
  • To determine if inhibiting ICE-like proteases can prevent cell death induced by anti-Fas antibody or TNF.

Main Methods:

  • Expression of crmA, an ICE inhibitor, in cells.
  • Treatment with an anti-Fas antibody or tumor necrosis factor (TNF).
  • Administration of a specific ICE inhibitor tetrapeptide (acetyl-Tyr-Val-Ala-Asp-chloromethylketone).

Main Results:

  • Expression of crmA inhibited cytotoxicity induced by both anti-Fas antibody and TNF.
  • The specific ICE inhibitor tetrapeptide also prevented apoptosis induced by anti-Fas antibody.
  • These findings indicate a critical role for ICE-like proteases in these cell death pathways.

Conclusions:

  • An ICE-like protease is involved in Fas-mediated apoptosis.
  • ICE-like proteases are implicated in TNF-induced cytotoxicity.
  • Targeting ICE-like proteases may offer therapeutic strategies for controlling apoptosis and cytotoxicity.

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