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
Titre
RhoE is a pro-survival p53 target gene that inhibits ROCK I-mediated apoptosis in response to genotoxic stress.
Périodique
Current biology
Auteur⸱e⸱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)
ISSN-L
0960-9822
Statut éditorial
Publié
Date de publication
19/12/2006
Peer-reviewed
Oui
Volume
16
Numéro
24
Pages
2466-2472
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Retracted Publication
Publication Status: ppublish
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, rho-Associated Kinases
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 14:59
Dernière modification de la notice
18/09/2024 10:27
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