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  • The EMBO Journal (2006) 25, 4084 - 4096
  • doi:10.1038/sj.emboj.7601292

Published online: 31 August 2006

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

Simone Di Giovanni1,2, Chad D Knights3, Mahadev Rao3, Alexander Yakovlev2, Jeannette Beers2, Jason Catania3, Maria Laura Avantaggiati3,4 and Alan I Faden2,4

  1. Laboratory for NeuroRegeneration and Repair, Hertie Institute for Clinical Brain Research, University of Tuebingen, Germany
  2. Department of Neuroscience, Georgetown University Medical Center, Washington DC, USA
  3. Lombardi Cancer Center, Georgetown University Medical Center, Washington DC, USA
  4. These authors contributed equally to this work

Correspondence to:

Simone Di Giovanni, Laboratory for NeuroRegeneration and Repair, Hertie Institute for Clinical Brain Research, University of Tuebingen, Otfried-Mueller Strasse 27, D-72076 Tuebingen, Germany. Tel.: +49 0 7071 29 80449; Fax: +49 0 7071 29 4521; E-mail: simone.digiovanni@medizin.uni-tuebingen.de

Maria Laura Avantaggiati, Lombardi Cancer Center, Georgetown University, 3970 Reservoir Road, Washington DC, 20057, USA. Tel.: +1 202 687 9199; Fax: +1 202 687 6402; E-mail: ma364@georgetown.edu

Received 23 February 2006; Accepted 27 July 2006

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.

  • Keywords:

    • axon regeneration,
    • coronin 1b,
    • neurite outgrowth,
    • p53,
    • Rab13