Regulation of Cdc42-mediated morphological effects: a novel function for p53

Gilles Gadéa1, Laure Lapasset, Cécile Gauthier-Rouvière

  • 1Centre de Recherche en Biochimie Macromoléculaire, CNRS UPR1086, IFR 24, 1919 route de Mende, F-34293 Montpellier cedex 5, France.

The EMBO Journal
|May 15, 2002
PubMed

Insights

The tumor suppressor p53 protein regulates cell shape and movement by controlling actin dynamics. This study reveals p53

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • The p53 protein is a critical tumor suppressor known for mediating cell cycle arrest and apoptosis.
  • Its established roles are vital for preventing uncontrolled cell proliferation and tumor formation.
  • However, the full spectrum of p53's functions in cellular processes remains under investigation.

Purpose of the Study:

  • To identify and characterize novel functions of the p53 protein beyond its canonical roles.
  • To investigate the specific impact of p53 on cell morphology and motility.
  • To elucidate the relationship between p53 and Rho GTPases (RhoA, Rac1, Cdc42) in regulating cellular architecture and movement.

Main Methods:

  • Utilized mouse embryonic fibroblasts (MEFs) to study the effects of p53.
  • Manipulated p53 levels through overexpression and deficiency models.
  • Assessed the impact of p53 on Cdc42-mediated filopodia formation, cell spreading on fibronectin, and Golgi reorientation during migration.

Main Results:

  • p53 selectively inhibited Cdc42-induced filopodia formation, with p53-deficient cells showing constitutive filopodia.
  • p53 overexpression modulated cell spreading on fibronectin.
  • Wild-type p53 expression abolished Golgi reorientation during cell migration, thereby preventing cell polarity establishment.

Conclusions:

  • p53 plays a previously unrecognized role in regulating cell morphology and movement.
  • This novel function involves the control of Cdc42-dependent actin cytoskeletal dynamics.
  • The identified role of p53 in cell movement regulation may contribute to its overall anti-tumorigenic activity.

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