JunD mediates survival signaling by the JNK signal transduction pathway

Mol Cell. 2003 Jun;11(6):1479-89. doi: 10.1016/s1097-2765(03)00203-x.

Abstract

The c-Jun NH(2)-terminal kinase (JNK) can cause cell death by activating the mitochondrial apoptosis pathway. However, JNK is also capable of signaling cell survival. The mechanism that accounts for the dual role of JNK in apoptosis and survival signaling has not been established. Here we demonstrate that JNK-stimulated survival signaling can be mediated by JunD. The JNK/JunD pathway can collaborate with NF-kappaB to increase antiapoptotic gene expression. This observation accounts for the ability of JNK to cause either survival or apoptosis in different cellular contexts. Furthermore, these data illustrate the general principal that signal transduction pathway integration is critical for the ability of cells to mount an appropriate biological response to a specific challenge.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Line
  • Cell Survival / physiology*
  • DNA Fragmentation
  • Enzyme Activation
  • Fibroblasts
  • Gene Expression Regulation
  • Genes, Reporter
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism*
  • Models, Biological
  • NF-kappa B / physiology
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Proto-Oncogene Proteins c-jun / physiology*
  • Signal Transduction*
  • Time Factors
  • Transcription, Genetic
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • NF-kappa B
  • Protein Isoforms
  • Proto-Oncogene Proteins c-jun
  • Tumor Necrosis Factor-alpha
  • Mitogen-Activated Protein Kinases