Abstract
The ability of p53 to promote apoptosis in response to mitogenic oncogenes appears to be critical for its tumor suppressor function. Caspase-9 and its cofactor Apaf-1 were found to be essential downstream components of p53 in Myc-induced apoptosis. Like p53 null cells, mouse embryo fibroblast cells deficient in Apaf-1 and caspase-9, and expressing c-Myc, were resistant to apoptotic stimuli that mimic conditions in developing tumors. Inactivation of Apaf-1 or caspase-9 substituted for p53 loss in promoting the oncogenic transformation of Myc-expressing cells. These results imply a role for Apaf-1 and caspase-9 in controlling tumor development.
Publication types
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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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Animals
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Apoptosis*
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Apoptotic Protease-Activating Factor 1
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Caspase 9
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Caspases / genetics
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Caspases / physiology*
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Cell Division
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Cell Transformation, Neoplastic
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Cells, Cultured
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Cytochrome c Group / metabolism
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Genes, myc
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Genes, p53*
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Genes, ras
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Mice
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Mice, Nude
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Mitochondria / metabolism
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Mutation
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Neoplasms, Experimental / genetics
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Neoplasms, Experimental / metabolism
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Neoplasms, Experimental / pathology*
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Proteins / genetics
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Proteins / physiology*
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Tumor Suppressor Protein p53 / metabolism
Substances
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Apaf1 protein, mouse
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Apoptotic Protease-Activating Factor 1
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Cytochrome c Group
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Proteins
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Tumor Suppressor Protein p53
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Casp9 protein, mouse
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Caspase 9
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Caspases