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J. Neurosci. 29 (16): 5183-5192

Copyright © 2009 by the Society for Neuroscience.

Development/Plasticity/Repair

A Novel Function for p53: Regulation of Growth Cone Motility through Interaction with Rho Kinase

Qingyu Qin,1 Michel Baudry,2 Guanghong Liao,1 Albert Noniyev,1 James Galeano,1 , and Xiaoning Bi1

1Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, California 91766, and 2Neuroscience Program, University of Southern California, Los Angeles, California 90089

Correspondence should be addressed to Dr. Xiaoning Bi, Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766-1854. Email: xbi{at}westernu.edu

Abstract: The transcription factor p53 suppresses tumorgenesis by regulating cell proliferation and migration. We investigated whether p53 could also control cell motility in postmitotic neurons. p53 isoforms recognized by phospho-p53-specific (at Ser-15) or "mutant" conformation-specific antibodies were highly and specifically expressed in axons and axonal growth cones in primary hippocampal neurons. Inhibition of p53 function by inhibitors, small interfering RNAs, or by dominant-negative forms, induced axonal growth cone collapse, whereas p53 overexpression led to larger growth cones. Furthermore, deletion of the p53 nuclear export signal blocked its axonal distribution and induced growth cone collapse. p53 inhibition-induced axonal growth cone collapse was significantly reduced by the Rho kinase (ROCK) inhibitor, Y27632 [(R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide]. Our results reveal a new function for p53 as a critical regulator of axonal growth cone behavior by suppressing ROCK activity.

Received for publication Jan. 26, 2009. Revision received March 8, 2009. Accepted for publication March 10, 2009.

Correspondence should be addressed to Dr. Xiaoning Bi, Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766-1854. Email: xbi{at}westernu.edu

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