Requirement of JNK for stress-induced activation of the cytochrome c-mediated death pathway

The c-Jun NH2-terminal kinase (JNK) is activated when cells are exposed to ultraviolet (UV) radiation. However, the functional consequence of JNK acti vation in UV-irradiated cells has not been established. It is shown here th at JNK is required for UV-induced apoptosis in primary murine embryonic fib roblasts. Fibroblasts with simultaneous targeted disruptions of all the fun ctional Jnk genes were protected against UV-stimulated apoptosis. The absen ce of JNK caused a defect in the mitochondrial death signaling pathway, inc luding the failure to release cytochrome c. These data indicate that mitoch ondria are influenced by proapoptotic signal transduction through the JNK p athway.