c-Jun expression, activation and function in neural cell death, inflammation and repair

J Neurochem. 2008 Nov;107(4):898-906. doi: 10.1111/j.1471-4159.2008.05684.x. Epub 2008 Sep 13.


Up-regulation of c-Jun is a common event in the developing, adult as well as in injured nervous system that serves as a model of transcriptional control of brain function. Functional studies employing in vivo strategies using gene deletion, targeted expression of dominant negative isoforms and pharmacological inhibitors all suggest a three pronged role of c-Jun action, exercising control over neural cell death and degeneration, in gliosis and inflammation as well as in plasticity and repair. In vitro, structural and molecular studies reveal several non-overlapping activation cascades via N-terminal c-Jun phosphorylation at serine 63 and 73 (Ser63, Ser73), and threonine 91 and 93 (Thr91, Thr93) residues, the dephosphorylation at Thr239, the p300-mediated lysine acetylation of the near C-terminal region (Lys268, Lys271, Lys 273), as well as the Jun-independent activities of the Jun N-terminal family of serine/threonine kinases, that regulate the different and disparate cellular responses. A better understanding of these non-overlapping roles in vivo could considerably increase the potential of pharmacological agents to improve neurological outcome following trauma, neonatal encephalopathy and stroke, as well as in neurodegenerative disease.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Death
  • Gene Expression / physiology*
  • Humans
  • Inflammation / complications
  • Inflammation / pathology*
  • Models, Biological
  • Neurons / physiology*
  • Proto-Oncogene Proteins c-jun / metabolism*
  • Recovery of Function / physiology*
  • Serine
  • Threonine


  • Proto-Oncogene Proteins c-jun
  • Threonine
  • Serine