Disruption of the CED-9·CED-4 complex by EGL-1 is a critical: Step for programmed cell death in Caenorhabditis elegans

Luis Del Peso, Víctor M. González, Naohiro Inohara, Ronald E. Ellis, Gabriel Núñez

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


In the nematode Caenorhabditis elegans, the apoptotic machinery is composed of four basic elements: the caspase CED-3, the Apaf-1 homologue CED-4, and the Bcl-2 family members CED-9 and EGL-1. The ced-9(n1950) gain-of-function mutation prevents most, if not all, somatic cell deaths in C. elegans. It encodes a CED-9 protein with a glycine-to-glutamate substitution at position 169, which is located within the highly conserved Bcl-2 homology 1 domain. We performed biochemical analyses with the CED-9G169E protein to gain insight into the mechanism of programmed cell death. We find that CED-9G169E retains the ability to bind both EGL-1 and CED-4, although its affinity for EGL-1 is reduced. In contrast to the behavior of wild-type CED-9, the interaction between CED-9G169E and CED-4 is not disrupted by expression of EGL-1. Furthermore, CED-4 and CED-9G169E co-localizes with EGL-1 to the mitochondria in mammalian cells, and expression of EGL-1 does not induce translocation of CED-4 to the cytosol. Finally, the ability of EGL-1 to promote apoptosis is impaired by the replacement of wild-type CED-9 with CED-9G169E, and this effect is correlated with the inability of EGL-1 to induce the displacement of CED-4 from the CED-9·CED-4 complex. These studies suggest that the release of CED-4 from the CED-9·CED-4 complex is a necessary step for induction of programmed cell death in C. elegans.

Original languageEnglish (US)
Pages (from-to)27205-27211
Number of pages7
JournalJournal of Biological Chemistry
Issue number35
StatePublished - Sep 1 2000
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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