The C. elegans protein EGL-1 is required for programmed cell death and interacts with the Bcl-2-like protein CED-9.
Gain-of-function mutations in the Caenorhabditis elegans gene egl-1 cause the HSN neurons to undergo programmed cell death. By contrast, a loss-of-function egl-1 mutation prevents most if not all somatic programmed cell deaths. The egl-1 gene negatively regulates the ced-9 gene, which protects against cell death and is a member of the bcl-2 family. The EGL-1 protein contains a nine amino acid region similar to the Bcl-2 homology region 3 (BH3) domain but does not contain a BH1, BH2, or BH4 domain, suggesting that EGL-1 may be a member of a family of cell death activators that includes the mammalian proteins Bik, Bid, Harakiri, and Bad. The EGL-1 and CED-9 proteins interact physically. We propose that EGL-1 activates programmed cell death by binding to and directly inhibiting the activity of CED-9, perhaps by releasing the cell death activator CED-4 from a CED-9/CED-4-containing protein complex.
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Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.
Horvitz
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D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000196:embryology / Q000235:genetics; D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000502:physiology; D020169:Caspases; D003001:Cloning, Molecular; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000502:physiology; D012734:Disorders of Sex Development / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D017238:Genes, Helminth / Q000235:genetics; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015183:Restriction Mapping; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013489:Suppression, 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; C112486:EGL-1 protein, C elegans; D015801:Helminth Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D020169:Caspases; D003546:Cysteine Endopeptidases; C089223:ced-3 protein, C elegans