Induction of Apoptosis in Fibroblasts by IL-1 Beta-Converting Enzyme, a Mammalian Homolog of the C. Elegans Cell Death Gene ced-3

Cell. 1993 Nov 19;75(4):653-60. doi: 10.1016/0092-8674(93)90486-a.

Abstract

The mammalian interleukin-1 beta-converting enzyme (ICE) has sequence similarity to the C. elegans cell death gene ced-3. We show here that overexpression of the murine ICE (mICE) gene or of the C. elegans ced-3 gene causes Rat-1 cells to undergo programmed cell death. Point mutations in a region homologous between mICE and CED-3 eliminate the ability of mICE and ced-3 to cause cell death. The cell death caused by mICE can be suppressed by overexpression of the crmA gene, a specific inhibitor of ICE, as well as by bcl-2, a mammalian oncogene that can act to prevent programmed cell death. Our results suggest that ICE may function during mammalian development to cause programmed cell death.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis*
  • Base Sequence
  • Caspase 1
  • Cell Line
  • DNA Primers / chemistry
  • In Vitro Techniques
  • Metalloendopeptidases / antagonists & inhibitors
  • Metalloendopeptidases / physiology*
  • Mice
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Proto-Oncogene Proteins / pharmacology
  • Proto-Oncogene Proteins c-bcl-2
  • Rats
  • Recombinant Fusion Proteins / metabolism
  • Serpins / metabolism
  • Viral Proteins*

Substances

  • DNA Primers
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Recombinant Fusion Proteins
  • Serpins
  • Viral Proteins
  • interleukin-1beta-converting enzyme inhibitor
  • Caspase 1
  • Metalloendopeptidases