The tumor suppressor protein p53 is required for neurite outgrowth and axon regeneration

Simone Di Giovanni, Chad D. Knights, Mahadev Rao, Alexander Yakovlev, Jeannette Beers, Jason Catania, Maria Laura Avantaggiati, Alan I. Faden

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155 Citations (Scopus)

Abstract

Axon regeneration is substantially regulated by gene expression and cytoskeleton remodeling. Here we show that the tumor suppressor protein p53 is required for neurite outgrowth in cultured cells including primary neurons as well as for axonal regeneration in mice. These effects are mediated by two newly identified p53 transcriptional targets, the actin-binding protein Coronin 1b and the GTPase Rab13, both of which associate with the cytoskeleton and regulate neurite outgrowth. We also demonstrate that acetylation of lysine 320 (K320) of p53 is specifically involved in the promotion of neurite outgrowth and in the regulation of the expression of Coronin 1b and Rab13. Thus, in addition to its recognized role in neuronal apoptosis, surprisingly, p53 is required for neurite outgrowth and axonal regeneration, likely through a different post-translational pathway. These observations may suggest a novel therapeutic target for promoting regenerative responses following peripheral or central nervous system injuries.

Original languageEnglish
Pages (from-to)4084-4096
Number of pages13
JournalEMBO Journal
Volume25
Issue number17
DOIs
Publication statusPublished - 06-09-2006

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Di Giovanni, S., Knights, C. D., Rao, M., Yakovlev, A., Beers, J., Catania, J., Avantaggiati, M. L., & Faden, A. I. (2006). The tumor suppressor protein p53 is required for neurite outgrowth and axon regeneration. EMBO Journal, 25(17), 4084-4096. https://doi.org/10.1038/sj.emboj.7601292