Translocation of C. elegans CED-4 to nuclear membranes during programmed cell death

Science. 2000 Feb 25;287(5457):1485-9. doi: 10.1126/science.287.5457.1485.

Abstract

The Caenorhabditis elegans Bcl-2-like protein CED-9 prevents programmed cell death by antagonizing the Apaf-1-like cell-death activator CED-4. Endogenous CED-9 and CED-4 proteins localized to mitochondria in wild-type embryos, in which most cells survive. By contrast, in embryos in which cells had been induced to die, CED-4 assumed a perinuclear localization. CED-4 translocation induced by the cell-death activator EGL-1 was blocked by a gain-of-function mutation in ced-9 but was not dependent on ced-3 function, suggesting that CED-4 translocation precedes caspase activation and the execution phase of programmed cell death. Thus, a change in the subcellular localization of CED-4 may drive programmed cell death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Animals
  • Animals, Genetically Modified
  • Apoptosis Regulatory Proteins
  • Apoptosis*
  • Caenorhabditis elegans / cytology*
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins*
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism*
  • Caspases*
  • Cysteine Endopeptidases / genetics
  • Cysteine Endopeptidases / metabolism
  • Genes, Helminth
  • Helminth Proteins / genetics
  • Helminth Proteins / metabolism*
  • Immunohistochemistry
  • Mitochondria / metabolism
  • Mutation
  • Nuclear Envelope / metabolism*
  • Phenotype
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-bcl-2
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • Caenorhabditis elegans Proteins
  • Calcium-Binding Proteins
  • Ced-4 protein, C elegans
  • Ced-9 protein, C elegans
  • EGL-1 protein, C elegans
  • Helminth Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Repressor Proteins
  • Caspases
  • Cysteine Endopeptidases
  • ced-3 protein, C elegans