Document Detail


A transcriptional cross-talk between RhoA and c-Myc inhibits the RhoA/Rock-dependent cytoskeleton.
MedLine Citation:
PMID:  20453885     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The GTPase RhoA participates in a number of cellular processes, including cytoskeletal organization, mitogenesis and tumorigenesis. We have previously shown that the transforming activity of an oncogenic version of RhoA (Q63L mutant) was highly dependent on the transcriptional factor c-Myc. In contrast to these positive effects in the RhoA route, we show here that c-Myc affects negatively the F-actin cytoskeleton induced by RhoA(Q63L) and its downstream effector, the serine/threonine kinase Rock. This effect entails the activation of a transcriptional program that requires synergistic interactions with RhoA-derived signals and that includes the upregulation of the GTPase Cdc42 and its downstream element Pak1 as well as the repression of specific integrin subunits. The negative effects of c-Myc in the F-actin cytoskeleton are eliminated by the establishment of cell-to-cell contacts, an effect associated with the rescue of Pak1 and integrin levels at the post-transcriptional and transcriptional levels, respectively. These results reveal the presence of a hitherto unknown signaling feed-back loop between RhoA and c--Myc oncogenes that can contribute to maintain fluid cytoskeletal dynamics in cancer cells.
Authors:
V Sauzeau; I M Berenjeno; C Citterio; X R Bustelo
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-05-10
Journal Detail:
Title:  Oncogene     Volume:  29     ISSN:  1476-5594     ISO Abbreviation:  Oncogene     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-02     Completed Date:  2010-07-19     Revised Date:  2011-09-26    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  3781-92     Citation Subset:  IM    
Affiliation:
Centro de Investigación del Cáncer, CSIC-University of Salamanca, Campus Unamuno, Salamanca, Spain.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cytoskeleton / metabolism*
Focal Adhesions
Mice
NIH 3T3 Cells
Proto-Oncogene Proteins c-myc / metabolism*
Transcription, Genetic*
rhoA GTP-Binding Protein / metabolism*
Grant Support
ID/Acronym/Agency:
5R01CA73735/CA/NCI NIH HHS; R01 CA073735-13/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Proto-Oncogene Proteins c-myc; EC 3.6.5.2/rhoA GTP-Binding Protein
Comments/Corrections

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