Abstract
Targeted gene disruption studies have established that the c-Jun NH(2)-terminal kinase (JNK) signaling pathway is required for stress-induced release of mitochondrial cytochrome c and apoptosis. Here we demonstrate that activated JNK is sufficient to induce rapid cytochrome c release and apoptosis. However, activated JNK fails to cause death in cells deficient of members of the Bax subfamily of proapoptotic Bcl2-related proteins. Furthermore, exposure to stress fails to activate Bax, cause cytochrome c release, and induce death in JNK-deficient cells. These data demonstrate that proapoptotic members of the Bax protein subfamily are essential for JNK-dependent apoptosis.
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 / physiology*
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Caspase 3
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Caspases / metabolism
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Cells, Cultured
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Cricetinae
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Cytochrome c Group / metabolism
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Enzyme Activation
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JNK Mitogen-Activated Protein Kinases
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MAP Kinase Kinase 7
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Membrane Proteins / metabolism
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Membrane Proteins / radiation effects
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Mice
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Mitochondria / metabolism
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Mitogen-Activated Protein Kinase Kinases / genetics
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Mitogen-Activated Protein Kinase Kinases / metabolism
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Mitogen-Activated Protein Kinases / genetics
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Mitogen-Activated Protein Kinases / metabolism*
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Phosphorylation
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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 / metabolism*
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Signal Transduction*
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Transcription Factor AP-1 / genetics
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Transcription Factor AP-1 / metabolism
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Ultraviolet Rays
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bcl-2 Homologous Antagonist-Killer Protein
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bcl-2-Associated X Protein
Substances
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Bak1 protein, mouse
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Bax protein, mouse
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Cytochrome c Group
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Membrane Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Recombinant Proteins
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Transcription Factor AP-1
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bcl-2 Homologous Antagonist-Killer Protein
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bcl-2-Associated X Protein
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases
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MAP Kinase Kinase 7
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MAP2K7 protein, human
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Map2k7 protein, mouse
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Mitogen-Activated Protein Kinase Kinases
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CASP3 protein, human
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Casp3 protein, mouse
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Caspase 3
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Caspases