Caenorhabditis elegans CED-4 stimulates CED-3 processing and CED-3-induced

We show that CED-9 achieves its anti-apoptotic effect by associating with CED-4 and blocking the ability of CED-4 to process CED-3

Somasekar Seshagiri; Lois K. Miller

2004

Scholarcy highlights

  • Programmed cell death or apoptosis is a key feature of normal development, tissue homeostasis and disease progression in metazoans
  • Stimulation of CED-3dependent apoptosis by CED-4 was accompanied by accelerated processing of CED-3, which was dependent on the presence of a wild-type CED-3 prodomain and a conserved lysine residue within a putative ATP/GTP-binding motif of CED-4
  • Co-expression of ced-9 with ced-4 and ced-3 inhibited the ability of CED-4 to stimulate CED-3 processing and CED-3-dependent apoptosis
  • We show that CED-9 achieves its anti-apoptotic effect by associating with CED-4 and blocking the ability of CED-4 to process CED-3
  • Our results indicate that the role of CED-4 in programmed cell death is to stimulate CED-3 processing, thereby generating an active caspase, and that the activity of CED-4 is regulated by its interaction with CED-9
  • The CED-3m pro-domain mutant acts as a null mutant of CED-3 in C. elegans, but has the same level of pro-apoptotic activity as wild type CED-3 when expressed alone in Sf-21 cells. The inability of this CED-3 mutant to respond to CED-4-mediated processing in Sf-21 cells suggests that CED-3m cannot be activated via its pro-domain, accounting for the null phenotype of this mutant in C. elegans
  • The association of CED-4 with CED-9 suggests that the stimulation of CED-3 processing by CED-4, and the ultimate fate of the cell, may be regulated by the relative expression levels of CED-4 and CED-9

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