The non-apoptotic role of p53 in neuronal biology: enlightening the dark side of the moon

EMBO Rep. 2009 Jun;10(6):576-83. doi: 10.1038/embor.2009.89. Epub 2009 May 8.


The transcription factor p53 protects neurons from transformation and DNA damage through the induction of cell-cycle arrest, DNA repair and apoptosis in a range of in vitro and in vivo conditions. Indeed, p53 has a crucial role in eliciting neuronal cell death during development and in adult organisms after exposure to a range of stressors and/or DNA damage. Nevertheless, accumulating evidence challenges this one-sided view of the role of p53 in the nervous system. Here, we discuss how-unexpectedly-p53 can regulate the proliferation and differentiation of neural progenitor cells independently of its role in apoptosis, and p53 post-translational modifications might promote neuronal maturation, as well as axon outgrowth and regeneration, following neuronal injury. We hope to encourage a more comprehensive view of the non-apoptotic functions of p53 during neural development, and to warn against oversimplifications regarding its role in neurons. In addition, we discuss how further insight into the p53-dependent modulation of these mechanisms is necessary to elucidate the decision-making processes between neuronal cell death and differentiation during development, and between neuronal degeneration and axonal regeneration after injury.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis*
  • Nervous System / embryology
  • Nervous System / metabolism
  • Neurons / cytology
  • Neurons / metabolism*
  • Protein Processing, Post-Translational
  • Signal Transduction
  • Stem Cells / metabolism
  • Tumor Suppressor Protein p53 / metabolism*


  • Tumor Suppressor Protein p53