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

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...

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Bibliographic Details
Published in:The EMBO journal 2006-09, Vol.25 (17), p.4084-4096
Main Authors: Di Giovanni, Simone, Knights, Chad D, Rao, Mahadev, Yakovlev, Alexander, Beers, Jeannette, Catania, Jason, Avantaggiati, Maria Laura, Faden, Alan I
Format: Article
Language:English
Subjects:
Acetylation
Animals
axon regeneration
Axons - physiology
Cells, Cultured
Central nervous system
coronin 1b
Cytoskeleton - physiology
EMBO24
EMBO27
Injuries
Lysine - metabolism
Male
Mice
Microfilament Proteins - metabolism
Molecular biology
Nerve Regeneration - physiology
neurite outgrowth
Neurites - physiology
Neurons
Neurons - physiology
Neurons - ultrastructure
p53
Proteins
rab GTP-Binding Proteins - metabolism
Rab13
Rats
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - metabolism
Tumor Suppressor Protein p53 - physiology
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Summary: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.
ISSN:0261-4189
1460-2075
DOI:10.1038/sj.emboj.7601292