Biology Reference
In-Depth Information
CHAPTER FOUR
Gatekeeper Between Quiescence
and Differentiation: p53 in Axonal
Outgrowth and Neurogenesis
Giorgia Quadrato, Simone Di Giovanni
1
Laboratory for NeuroRegeneration and Repair, Center for Neurology, Hertie Institute for Clinical Brain
Research, University of Tuebingen, Tuebingen, Germany
1
Corresponding author: e-mail address: simone.digiovanni@medizin.uni-tuebingen.de
Contents
1.
Introduction
71
2. p53 in Neural Development and Neural Stem Cell Regulation
73
3. p53 in Neurite Growth and Axonal Regeneration
75
4. Effects of Posttranslational Modifications on p53 Function
80
5. Conclusions and Perspectives
82
Acknowledgments
84
References
85
Abstract
The transcription factor and tumor suppressor gene p53 regulates a wide range of cellular
processes including DNA damage/repair, cell cycle progression, apoptosis, and cell
metabolism. In the past several years, a specific novel role for p53 in neuronal biology
has emerged. p53 orchestrates the polarity of self-renewing divisions in neural stem cells
both during embryonic development and in adulthood and coordinates the timing for
cell fate specification. In postmitotic neurons, p53 regulates neurite outgrowth and post-
injury axonal regeneration via neurotrophin-dependent and -independent signaling by
both transcriptional and posttranslational control of growth cone remodeling. This review
provides an insight into the molecular mechanisms upstream and downstream p53 both
during neural development and following axonal injury. Their understandingmay provide
therapeutic targets to enhance neuroregeneration following nervous system injury.
1. INTRODUCTION
p53 also known as “the guardian of the genome” is a transcription
factor initially identified as a tumor suppressor gene and then later described
as an ubiquitous regulator of cell cycle progression, polarity, proliferation,
