Developing Caenorhabditis elegans neurons may contain both cell-death protective and killer activities.
We developed a method for examining the effects of overexpressing cell-death-related genes in specific Caenorhabditis elegans neurons that normally live. Using this method, we demonstrated that the cell-death genes ced-3, ced-4, and ced-9 all can act cell autonomously to control programmed cell death. Our observations indicate further that not only the protective activity of ced-9 but also the killer activities of ced-3 and ced-4 are likely to be present in cells that normally live. We propose that both in C. elegans and in other organisms a competition between antagonistic protective and killer activities determines whether specific cells will live or die. Our results suggest a genetic pathway for programmed cell death in C. elegans in which ced-4 acts upstream of or in parallel to ced-3 and ced-9 negatively regulates the activity of ced-4.
Shaham
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Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, 02139, USA.
Horvitz
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D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D020169:Caspases; D002470:Cell Survival; D017238:Genes, Helminth; D015801:Helminth Proteins / Q000096:biosynthesis / Q000235:genetics*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D009474:Neurons / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins / Q000096:biosynthesis; D014170:Transformation, Genetic
D051017:Apoptosis Regulatory Proteins; D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins; C089224:Ced-4 protein, C elegans; C087233:Ced-9 protein, C elegans; D015801:Helminth Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D020169:Caspases; C089223:ced-3 protein, C elegans