The non-apoptotic role of p53 in neuronal biology: enlightening the dark side of the moon.
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.
Tedeschi
Andrea
A
Laboratory for NeuroRegeneration and Repair, Department of Neurology, Hertie Institute for Clinical Brain Research, University of Tuebingen, Otfried-Mueller Strasse 27, Tuebingen D-72076, Germany.
Di Giovanni
Simone
S
D000818:Animals; D017209:Apoptosis; D009420:Nervous System / Q000196:embryology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53