RhoE is a pro-survival p53 target gene that inhibits ROCK I-mediated apoptosis in response to genotoxic stress

Détails

ID Serval
serval:BIB_5B167F0FDD75
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
RhoE is a pro-survival p53 target gene that inhibits ROCK I-mediated apoptosis in response to genotoxic stress
Périodique
Current Biology
Auteur(s)
Ongusaha  P. P., Kim  H. G., Boswell  S. A., Ridley  A. J., Der  C. J., Dotto  G. P., Kim  Y. B., Aaronson  S. A., Lee  S. W.
ISSN
0960-9822 (Print)
Statut éditorial
Publié
Date de publication
12/2006
Volume
16
Numéro
24
Pages
2466-72
Notes
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't --- Old month value: Dec 19
Résumé
The Rho family of GTPases regulates many aspects of cellular behavior through alterations to the actin cytoskeleton . The majority of the Rho family proteins function as molecular switches cycling between the active, GTP-bound and the inactive, GDP-bound conformations . Unlike typical Rho-family proteins, the Rnd subfamily members, including Rnd1, Rnd2, RhoE (also known as Rnd3), and RhoH, are GTPase deficient and are thus expected to be constitutively active . Here, we identify an unexpected role for RhoE/Rnd3 in the regulation of the p53-mediated stress response. We show that RhoE is a transcriptional p53 target gene and that genotoxic stress triggers actin depolymerization, resulting in actin-stress-fiber disassembly through p53-dependent RhoE induction. Silencing of RhoE induction in response to genotoxic stress maintains stress fiber formation and strikingly increases apoptosis, implying an antagonistic role for RhoE in p53-dependent apoptosis. We found that RhoE inhibits ROCK I (Rho-associated kinase I) activity during genotoxic stress and thereby suppresses apoptosis. We demonstrate that the p53-mediated induction of RhoE in response to DNA damage favors cell survival partly through inhibition of ROCK I-mediated apoptosis. Thus, RhoE is anticipated to function by regulating ROCK I signaling to control the balance between cell survival and cell death in response to genotoxic stress.
Mots-clé
Animals *Apoptosis Cell Line Cell Line, Tumor Cell Survival *DNA Damage Fibroblasts Gene Expression Profiling Genes, p53 Humans Intracellular Signaling Peptides and Proteins/metabolism Mice Protein-Serine-Threonine Kinases/metabolism Signal Transduction Tumor Suppressor Protein p53/*metabolism Up-Regulation rho GTP-Binding Proteins/*metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 15:59
Dernière modification de la notice
20/08/2019 15:14
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