The c-Jun transcription factor--bipotential mediator of neuronal death, survival and regeneration

Trends Neurosci. 1997 May;20(5):227-31. doi: 10.1016/s0166-2236(96)01000-4.


Axon interruption elicits a complex neuronal response that leaves neurons poised precariously between death and regeneration. The signals underlying this dichotomy are not fully understood. The transcription factor c-Jun is one of the earliest and most consistent markers for neurons that respond to nerve-fiber transection, and its expression can be related to both degeneration and survival including target re-innervation. In vitro experiments have demonstrated that expression of c-Jun can kill neonatal neurons but, in the adult nervous system, c-Jun might also be involved in neuroprotection and regeneration. The functional characteristics of c-Jun offer a model for the ability of a single molecule to serve as pivotal regulator for death or survival, not only in the response of the cell body to axonal lesions but also following neurodegenerative disorders. In this model, the fate of neurons is determined by a novel transcriptional network comprising c-Jun, ATF-2 (activating transcription factor-2) and JNKs (c-Jun N-terminal kinases).

Publication types

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

MeSH terms

  • Animals
  • Axons / physiology
  • Cell Death / physiology
  • Denervation
  • Enzyme Activation
  • Humans
  • JNK Mitogen-Activated Protein Kinases*
  • MAP Kinase Kinase 4
  • Mitogen-Activated Protein Kinase Kinases*
  • Nerve Regeneration / physiology*
  • Neurons / physiology*
  • Protein Kinases / metabolism
  • Proto-Oncogene Proteins c-jun / physiology*


  • Proto-Oncogene Proteins c-jun
  • Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • Mitogen-Activated Protein Kinase Kinases