Abstract
Previous genetic studies of the nematode Caenorhabditis elegans identified three important components of the cell death machinery. CED-3 and CED-4 function to kill cells, whereas CED-9 protects cells from death. Here CED-9 and its mammalian homolog Bcl-xL (a member of the Bcl-2 family of cell death regulators) were both found to interact with and inhibit the function of CED-4. In addition, analysis revealed that CED-4 can simultaneously interact with CED-3 and its mammalian counterparts interleukin-1beta-converting enzyme (ICE) and FLICE. Thus, CED-4 plays a central role in the cell death pathway, biochemically linking CED-9 and the Bcl-2 family to CED-3 and the ICE family of pro-apoptotic cysteine proteases.
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 / metabolism
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Caenorhabditis elegans Proteins*
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Calcium-Binding Proteins / genetics
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Calcium-Binding Proteins / metabolism*
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Caspase 1
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Caspase 8
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Caspase 9
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Caspases*
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Cell Line
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Cysteine Endopeptidases / genetics
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Cysteine Endopeptidases / metabolism*
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Genes, Helminth
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Helminth Proteins / genetics
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Helminth Proteins / metabolism*
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Humans
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Mutation
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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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Tumor Cells, Cultured
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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
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CASP8 protein, human
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CASP9 protein, human
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Caspase 8
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Caspase 9
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Caspases
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Cysteine Endopeptidases
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ced-3 protein, C elegans
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Caspase 1