A novel function for p53: regulation of growth cone motility through interaction with Rho kinase.
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.
Qin
Qingyu
Q
Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, California 91766-1854, USA.
Baudry
Michel
M
Liao
Guanghong
G
Noniyev
Albert
A
Galeano
James
J
Bi
Xiaoning
X
D000818:Animals; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D020439:Growth Cones / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology; D011485:Protein Binding / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
D016159:Tumor Suppressor Protein p53; D054460:rho-Associated Kinases