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

被引:189
作者
Di Giovanni, Simone
Knights, Chad D.
Rao, Mahadev
Yakovlev, Alexander
Beers, Jeannette
Catania, Jason
Avantaggiati, Maria Laura
Faden, Alan I.
机构
[1] Univ Tubingen, Lab NeuroRegenerat & Repair, Hertie Inst Clin Brain Res, D-72076 Tubingen, Germany
[2] Georgetown Univ, Med Ctr, Dept Neurosci, Washington, DC 20007 USA
[3] Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA
关键词
axon regeneration; coronin; 1b; neurite outgrowth; p53; Rab13;
D O I
10.1038/sj.emboj.7601292
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:4084 / 4096
页数:13
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