RhoE is a pro-survival p53 target gene that inhibits ROCK I-mediated apoptosis in response to genotoxic stress
Details
Serval ID
serval:BIB_5B167F0FDD75
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
RhoE is a pro-survival p53 target gene that inhibits ROCK I-mediated apoptosis in response to genotoxic stress
Journal
Current Biology
ISSN
0960-9822 (Print)
Publication state
Published
Issued date
12/2006
Volume
16
Number
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
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't --- Old month value: Dec 19
Abstract
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.
Keywords
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
Yes
Create date
24/01/2008 15:59
Last modification date
20/08/2019 15:14