Interaction and regulation of subcellular localization of CED-4 by CED-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.
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Department of Pathology and Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Wallen
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Nuñez
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D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002458:Cell Fractionation; D002460:Cell Line; D003600:Cytosol / Q000737:chemistry; D017238:Genes, Helminth; D015801:Helminth Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007425:Intracellular Membranes / Q000737:chemistry; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D014162:Transfection; D051020:bcl-X Protein
D051017:Apoptosis Regulatory Proteins; C494811:BCL2L1 protein, human; 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; D051020:bcl-X Protein