Abstract
Genetic analyses of Caenorhabditis elegans has identified three genes that function in the regulation of nematode cell death. Mammalian homologs of two of these genes, ced-9 and ced-3, have been identified and comprise proteins belonging to the Bcl-2 and ICE families, respectively. To date, it is unclear where the negative regulators, ced-9 and bcl-2, function relative to the death effectors, ced-3 and the mammalian ced-3 homologs, respectively. Here, the molecular order of the cell death pathway is defined. Our results establish that Bcl-2 and Bcl-xL function upstream of two members of the ICE/CED-3 family of cysteine proteases, Yama (CPP32/apopain) and ICE-LAP3 (Mch3).
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Antibodies
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Apoptosis / genetics*
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Caenorhabditis elegans / genetics*
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Caenorhabditis elegans / physiology*
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Caenorhabditis elegans Proteins
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Caspases*
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Cell Line
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Cysteine Endopeptidases / biosynthesis
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Cysteine Endopeptidases / genetics
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Gene Expression Regulation
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Genes, Helminth*
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Helminth Proteins / biosynthesis
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Helminth Proteins / genetics*
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Humans
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Immunoblotting
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Mammals
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Models, Biological
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Molecular Sequence Data
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Peptides / chemical synthesis
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Peptides / immunology
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Protein-Tyrosine Kinases / genetics
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Proto-Oncogene Proteins / biosynthesis
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Proto-Oncogene Proteins / genetics*
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Proto-Oncogene Proteins c-bcl-2
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Proto-Oncogenes
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bcl-X Protein
Substances
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Antibodies
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BCL2L1 protein, human
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Caenorhabditis elegans Proteins
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Helminth Proteins
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Peptides
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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bcl-X Protein
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Protein-Tyrosine Kinases
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Caspases
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Cysteine Endopeptidases
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ced-3 protein, C elegans