Regulation of Cdc42-mediated morphological effects: a novel function for p53
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Updated: Oct 1, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
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.
Abstract:
The tumour suppressor functions of p53 that are important for its activity depend on its role as a cell cycle arrest mediator and apoptosis inducer. Here we identify a novel function for p53 in regulating cell morphology and movement. We investigated the overall effect of p53 on morphological changes induced by RhoA, Rac1 and Cdc42 GTPases in mouse embryonic fibroblasts (MEFs). Interestingly, p53 exerted a selective effect on Cdc42-mediated cell functions. (i) Both overexpression of wild-type p53 and activation of endogenous p53 counteracted Cdc42-induced filopodia formation. Conversely, p53-deficient MEFs exhibited constitutive membrane filopodia. Mechanistic studies indicate that p53 prevents the initiating steps of filopodia formation downstream of Cdc42. (ii) Over expression of p53 modulates cell spreading of MEFs on fibronectin. (iii) During cell migration, the reorientation of the Golgi apparatus in the direction of movement is abolished by wild-type p53 expression, thus preventing cell polarity. Our data demonstrate a previously uncharacterized role for p53 in regulating Cdc42-dependent cell effects that control actin cytoskeletal dynamics and cell movement. This novel function may contribute to p53 anti-tumour activity.
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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