Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Apoptosis / physiology*
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Apoptosis Regulatory Proteins
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Base Sequence
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Caenorhabditis elegans / cytology*
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Caenorhabditis elegans / embryology
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Caenorhabditis elegans / genetics
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Caenorhabditis elegans Proteins*
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Calcium-Binding Proteins / genetics
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Calcium-Binding Proteins / physiology
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Caspases*
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Cloning, Molecular
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Cysteine Endopeptidases / genetics
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Cysteine Endopeptidases / physiology
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Disorders of Sex Development / genetics
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Gene Expression Regulation, Developmental / physiology
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Genes, Helminth / genetics
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Helminth Proteins / genetics
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Helminth Proteins / metabolism*
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Helminth Proteins / physiology
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Molecular Sequence Data
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Neurons / cytology
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Recombinant Fusion Proteins
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Repressor Proteins / genetics
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Repressor Proteins / metabolism
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Repressor Proteins / physiology*
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Restriction Mapping
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Sequence Analysis, DNA
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Sequence Homology, Amino Acid
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Suppression, Genetic
Substances
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Apoptosis Regulatory Proteins
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Caenorhabditis elegans Proteins
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Calcium-Binding Proteins
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Ced-4 protein, C elegans
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Ced-9 protein, C elegans
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EGL-1 protein, C elegans
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Helminth Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Recombinant Fusion Proteins
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Repressor Proteins
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Caspases
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Cysteine Endopeptidases
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ced-3 protein, C elegans