NF-κB is required for UV-induced JNK activation via induction of PKCδ

Ultraviolet (UV) exerts its biological activities by activating downstream effectors, including NF-kappa B, JNK, and caspases. Activation of JNK is required for UV-induced apoptosis. It is unknown whether any crosstalk occurs between NF-kappa B and JNK in response to UV and, if so, how it affects UV killing. Here we report that NF-kappa B promotes UV-induced JNK activation, thereby contributing to UV-induced apoptosis. UV-induced JNK activation is impaired in ReIA/NF-kappa B null murine embryonic fibroblasts. In resting cells, the preexisting nuclear ReIA has already been recruited to PKC delta promoter and is essential for its expression. UV-induced rapid and robust activation of JNK requires PKC delta, which augments JNK phosphorylation-activation by its upstream kinases. The ReIA/NF-kappa B-PKC delta-JNK pathway is critical for UV-induced apoptosis, as it induces the immediate expression of the proapoptotic Fas ligand. Thus, our results demonstrate that ReIA/NF-kappa B via PKC delta positively regulates UV-induced JNK activation and provide a mechanism by which NF-kappa B promotes UV-induced apoptosis.