Gatekeeper between quiescence and differentiation: p53 in axonal outgrowth and neurogenesis

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 postinjury 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 understanding may provide therapeutic targets to enhance neuroregeneration following nervous system injury.