NF-kappaB is required for UV-induced JNK activation via induction of PKCdelta

Mol Cell. 2006 Feb 17;21(4):467-80. doi: 10.1016/j.molcel.2005.12.020.

Abstract

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

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis / radiation effects*
  • Cells, Cultured
  • Enzyme Activation
  • Fas Ligand Protein
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Fibroblasts / radiation effects
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Knockout
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Protein Kinase C-delta / metabolism*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction / physiology
  • Transcription Factor RelA / genetics
  • Transcription Factor RelA / metabolism
  • Tumor Necrosis Factors / metabolism
  • Ultraviolet Rays

Substances

  • Fas Ligand Protein
  • Fasl protein, mouse
  • Membrane Glycoproteins
  • NF-kappa B
  • RNA, Small Interfering
  • Rela protein, mouse
  • Transcription Factor RelA
  • Tumor Necrosis Factors
  • Protein Kinase C-delta
  • JNK Mitogen-Activated Protein Kinases