Requirement of JNK for stress-induced activation of the cytochrome c-mediated death pathway
Howard Hughes Medical Institute and Program in Molecular Medicine; Department of Biochemistry and Molecular Pharmacology; Department of Cell Biology
Animals; *Apoptosis; Apoptotic Protease-Activating Factor 1; Caspase 3; Caspase 9; Caspases; Cell Count; Cell Division; Cells, Cultured; Cytochrome c Group; DNA Fragmentation; Enzyme Activation; Fibroblasts; Gene Targeting; JNK Mitogen-Activated Protein Kinases; MAP Kinase Signaling System; Methyl Methanesulfonate; Mice; Mitochondria; Mitogen-Activated Protein Kinases; NF-kappa B; *Protein-Serine-Threonine Kinases; Proteins; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-bcl-2; Tumor Suppressor Protein p53; Ultraviolet Rays
Life Sciences | Medicine and Health Sciences
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.
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Citation: Science. 2000 May 5;288(5467):870-4.
Science (New York, N.Y.)
Tournier, Cathy; Hess, Patricia M.; Yang, Derek D.; Xu, Jie; Turner, Tod K.; Nimnual, Anjaruwee S.; Bar-Sagi, Dafna; Jones, Stephen N.; Flavell, Richard A.; and Davis, Roger J., "Requirement of JNK for stress-induced activation of the cytochrome c-mediated death pathway" (2000). Open Access Articles. 1641.