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Wu, D, Wallen, HD and Nuñez, G (1997) Interaction and regulation of subcellular localization of CED-4 by CED-9. Science 275:1126-9
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.
Animals; Apoptosis; Apoptosis Regulatory Proteins; Caenorhabditis elegans/cytology; Caenorhabditis elegans/genetics; Caenorhabditis elegans Proteins; Calcium-Binding Proteins/analysis; Calcium-Binding Proteins/genetics; Calcium-Binding Proteins/metabolism; Cell Fractionation; Cell Line; Cytosol/chemistry; Genes, Helminth; Helminth Proteins/analysis; Helminth Proteins/genetics; Helminth Proteins/metabolism; Humans; Intracellular Membranes/chemistry; Mutation; Proto-Oncogene Proteins/analysis; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/metabolism; Proto-Oncogene Proteins c-bcl-2; Transfection; bcl-X Protein
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