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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Published inThe EMBO journal Vol. 25; no. 17; pp. 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 Journal Article
LanguageEnglish
Published Chichester, UK John Wiley & Sons, Ltd 06.09.2006
Blackwell Publishing Ltd
Subjects
Acetylation
Animals
axon regeneration
Axons - physiology
Cells, Cultured
coronin 1b
Cytoskeleton - physiology
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.
Bibliography:ark:/67375/WNG-BWTWLDCK-G
istex:C80713E136578F63B271F453B042189BA11153C3
ArticleID:EMBJ7601292
Supplementary Figure S1Supplementary Figure S2Supplementary Figure LegendsSupplementary Materials
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0261-4189
1460-2075
DOI:10.1038/sj.emboj.7601292