Abstract
The Caenorhabditis elegans survival gene ced-9 regulates ced-4 activity and inhibits cell death, but the mechanism by which this occurs is unknown. Through a genetic screen for CED-4-binding proteins, CED-9 was identified as an interacting partner of CED-4. CED-9, but not loss-of-function mutants, associated specifically with CED-4 in yeast or mammalian cells. The CED-9 protein localized primarily to intracellular membranes and the perinuclear region, whereas CED-4 was distributed in the cytosol. Expression of CED-9, but not a mutant lacking the carboxy-terminal hydrophobic domain, targeted CED-4 from the cytosol to intracellular membranes in mammalian cells. Thus, the actions of CED-4 and CED-9 are directly linked, which could provide the basis for the regulation of programmed cell death in C. elegans.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Apoptosis Regulatory Proteins
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Apoptosis*
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Caenorhabditis elegans / cytology*
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Caenorhabditis elegans / genetics
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Caenorhabditis elegans Proteins*
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Calcium-Binding Proteins / analysis
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Calcium-Binding Proteins / genetics
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Calcium-Binding Proteins / metabolism*
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Cell Fractionation
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Cell Line
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Cytosol / chemistry
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Genes, Helminth
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Helminth Proteins / analysis
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Helminth Proteins / genetics
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Helminth Proteins / metabolism*
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Humans
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Intracellular Membranes / chemistry
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Mutation
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Proto-Oncogene Proteins / analysis
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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*
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Transfection
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bcl-X Protein
Substances
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Apoptosis Regulatory Proteins
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BCL2L1 protein, human
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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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Helminth Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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bcl-X Protein