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Requirement of JNK for Stress- Induced Activation of the Cytochrome c-Mediated Death Pathway

Science  05 May 2000:
Vol. 288, Issue 5467, pp. 870-874
DOI: 10.1126/science.288.5467.870

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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 Jnkgenes 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.

  • * Present address: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA.

  • To whom correspondence should be addressed. E-mail: Roger.Davis{at}umassmed.edu

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