Inhibition of the Caenorhabditis Elegans Cell-Death Protease CED-3 by a CED-3 Cleavage Site in Baculovirus p35 Protein

Nature. 1995 Sep 21;377(6546):248-51. doi: 10.1038/377248a0.

Abstract

The baculovirus protein p35 inhibits programmed cell death in such diverse animals as insects, nematodes and mammals. Here we show that p35 protein is a substrate for and inhibitor of the Caenorhabditis elegans cell-death protease CED-3 (refs 6, 7) and a substrate for four CED-3-like vertebrate cysteine protease activities implicated in apoptosis in mammals. A p35 mutation that greatly reduced p35 activity in vitro as a CED-3 substrate and inhibitor abolished p35 activity in vivo in protecting against cell death in C. elegans. Introduction of the CED-3 cleavage site in p35 into the cowpox virus protein crmA, which inhibits mammalian apoptosis but not programmed cell death in C. elegans, caused crmA to block CED-3-mediated cell death. These observations suggest that p35 may prevent programmed cell death in C. elegans and other species by acting as a competitive inhibitor of cysteine proteases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Apoptosis*
  • Baculoviridae
  • Base Sequence
  • Binding Sites
  • Binding, Competitive
  • Caenorhabditis elegans / enzymology*
  • Caenorhabditis elegans Proteins
  • Caspase 1
  • Caspases*
  • Cysteine Endopeptidases / metabolism
  • Cysteine Proteinase Inhibitors / metabolism*
  • DNA Primers
  • Helminth Proteins / antagonists & inhibitors*
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Mice
  • Molecular Sequence Data
  • Mutagenesis
  • Recombinant Fusion Proteins / metabolism
  • Serpins / metabolism
  • Viral Proteins / chemistry
  • Viral Proteins / genetics
  • Viral Proteins / metabolism*

Substances

  • Caenorhabditis elegans Proteins
  • Cysteine Proteinase Inhibitors
  • DNA Primers
  • Helminth Proteins
  • Inhibitor of Apoptosis Proteins
  • Recombinant Fusion Proteins
  • Serpins
  • Viral Proteins
  • inhibitor of apoptosis, Nucleopolyhedrovirus
  • interleukin-1beta-converting enzyme inhibitor
  • Caspases
  • Cysteine Endopeptidases
  • ced-3 protein, C elegans
  • Caspase 1