Differential effects of JNK1 and JNK2 on signal specific induction of apoptosis

Oncogene. 2002 Apr 4;21(15):2441-5. doi: 10.1038/sj.onc.1205348.


The c-Jun N-terminal kinases (JNKs) are activated by a variety of stress inducing agents and are thought to regulate apoptosis in a cell type and signal-specific manner. We have used fibroblasts lacking JNK1 or JNK2 to define their roles in response to different stress signals. Lack of JNK1 results in reduced c-Jun phosphorylation and resistance to UV-induced cell death. JNK2 deficient cells show increased sensitivity to UV irradiation which correlates with elevated and sustained phosphorylation of JNK1 and c-Jun. On the contrary, both Jnk1-/- and Jnk2-/- cells were more sensitive to tumor necrosis factor - alpha (TNF-alpha) and sorbitol-induced cell death. Treatment of Jnk1-/- cells with these reagents resulted in reduced JNK activity and a concomitant reduction of c-Jun phosphorylation, suggesting that phosphorylation of c-Jun does not influence TNF-alpha and sorbitol-induced apoptosis in fibroblasts. Moreover, both JNK1 and JNK2 appear to negatively regulate apoptosis independent of c-Jun phosphorylation. These data provide genetic evidence that although the JNK pathway is activated by a plethora of signals, it is required only for the induction of UV-induced cell death in a c-Jun phosphorylation-dependent manner, but not for TNF-alpha and sorbitol-induced apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Cell Line, Transformed
  • Cells, Cultured
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Fibroblasts / radiation effects
  • Gene Deletion
  • MAP Kinase Signaling System*
  • Mitogen-Activated Protein Kinase 8
  • Mitogen-Activated Protein Kinase 9
  • Mitogen-Activated Protein Kinases / genetics
  • Mitogen-Activated Protein Kinases / physiology*
  • Models, Biological
  • Phosphorylation
  • Proto-Oncogene Proteins c-jun / metabolism
  • Sorbitol / pharmacology
  • Tumor Necrosis Factor-alpha / pharmacology
  • Ultraviolet Rays


  • Proto-Oncogene Proteins c-jun
  • Tumor Necrosis Factor-alpha
  • Sorbitol
  • Mitogen-Activated Protein Kinase 9
  • Mitogen-Activated Protein Kinase 8
  • Mitogen-Activated Protein Kinases