Abstract
The c-Jun NH2-terminal kinase (JNK) is activated when cells are exposed to ultraviolet (UV) radiation. However, the functional consequence of JNK activation in UV-irradiated cells has not been established. It is shown here that JNK is required for UV-induced apoptosis in primary murine embryonic fibroblasts. Fibroblasts with simultaneous targeted disruptions of all the functional Jnk genes were protected against UV-stimulated apoptosis. The absence of JNK caused a defect in the mitochondrial death signaling pathway, including the failure to release cytochrome c. These data indicate that mitochondria are influenced by proapoptotic signal transduction through the JNK pathway.
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*
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Apoptotic Protease-Activating Factor 1
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Caspase 3
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Caspase 9
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Caspases / metabolism
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Cell Count
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Cell Division
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Cells, Cultured
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Cytochrome c Group / metabolism*
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DNA Fragmentation
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Enzyme Activation
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Fibroblasts
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Gene Targeting
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JNK Mitogen-Activated Protein Kinases
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MAP Kinase Signaling System
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Methyl Methanesulfonate / pharmacology
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Mice
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Mitochondria / metabolism
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Mitogen-Activated Protein Kinases / genetics
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Mitogen-Activated Protein Kinases / metabolism*
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NF-kappa B / metabolism
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Protein Serine-Threonine Kinases*
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Proteins / metabolism
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-akt
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Tumor Suppressor Protein p53 / metabolism
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Ultraviolet Rays
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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NF-kappa B
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Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Tumor Suppressor Protein p53
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Methyl Methanesulfonate
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases
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Casp3 protein, mouse
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Casp9 protein, mouse
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Caspase 3
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Caspase 9
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Caspases