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 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.
Di Giovanni
Simone
S
Laboratory for NeuroRegeneration and Repair, Hertie Institute for Clinical Brain Research, University of Tuebingen, Germany. simone.digiovanni@medizin.uni-tuebingen.de
Knights
Chad D
CD
Rao
Mahadev
M
Yakovlev
Alexander
A
Beers
Jeannette
J
Catania
Jason
J
Avantaggiati
Maria Laura
ML
Faden
Alan I
AI
D000107:Acetylation; D000818:Animals; D001369:Axons / Q000502:physiology*; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000502:physiology; D008239:Lysine / Q000378:metabolism; D008297:Male; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism*; D009416:Nerve Regeneration / Q000502:physiology*; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000502:physiology / Q000648:ultrastructure; D051381:Rats; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020691:rab GTP-Binding Proteins / Q000378:metabolism*
D008840:Microfilament Proteins; D016159:Tumor Suppressor Protein p53; C072061:coronin proteins; C484177:Rab13 protein, mouse; D020691:rab GTP-Binding Proteins; D008239:Lysine