Document Detail

Gbetagamma is a negative regulator of AP-1 mediated transcription.
MedLine Citation:
PMID:  20403427     Owner:  NLM     Status:  MEDLINE    
Following stimulation of G protein-coupled receptors (GPCRs) at the cell surface, heterotrimeric G proteins are activated. Both Galpha and Gbetagamma subunits regulate specific effectors to transmit signals received by the receptor. Recent data suggest potential nuclear localization or translocation of the Gbetagamma subunit. Here, we show that co-expression of the Gbetagamma dimer decreased phorbol 12-myristate 13-acetate (PMA)-stimulated AP-1 gene reporter activity in HEK293 cells as well as the AP-1 dependent gonadotropin-releasing hormone-stimulated human follicle-stimulating hormone beta reporter activity in LbetaT2 gonadotrope cells. Further, we identify Fos transcription factors as novel interactors of the Gbeta1 subunit, using protein fragment complementation assays, as well as co-immunoprecipitation in vivo and in vitro. Fos proteins dimerize with Jun proteins to form activator protein-1 (AP-1) transcription factor complexes, which regulate target gene expression. Gbetagamma did not interfere with the dimerization of Fos and Jun or their ability to bind DNA. Rather, Gbetagamma co-localized with the AP-1 complex in the nucleus and recruited histone deacetylases (HDACs) to inhibit AP-1 transcriptional activity. Our data indicate a novel role for Gbetagamma subunits as transcriptional regulators.
M?lanie Robitaille; Sarah Gora; Ying Wang; Eug?nie Goupil; Darlaine P?trin; Danny Del Duca; Louis R Villeneuve; Bruce G Allen; St?phane A Laporte; Daniel J Bernard; Terence E H?bert
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-04-18
Journal Detail:
Title:  Cellular signalling     Volume:  22     ISSN:  1873-3913     ISO Abbreviation:  Cell. Signal.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-05-24     Completed Date:  2010-06-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8904683     Medline TA:  Cell Signal     Country:  England    
Other Details:
Languages:  eng     Pagination:  1254-66     Citation Subset:  IM    
D?partement de Biochimie, Universit? de Montr?al, Montr?al, Qu?bec, Canada.
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MeSH Terms
Cell Line
Cell Nucleus / chemistry
GTP-Binding Protein beta Subunits / analysis,  metabolism*
GTP-Binding Protein gamma Subunits / analysis,  metabolism*
Proto-Oncogene Proteins c-fos / metabolism
Transcription Factor AP-1 / antagonists & inhibitors*,  metabolism
Transcription, Genetic*
Grant Support
MOP-36279//Canadian Institutes of Health Research; MOP-79354//Canadian Institutes of Health Research; MOP-89991//Canadian Institutes of Health Research
Reg. No./Substance:
0/G-protein Beta gamma; 0/GTP-Binding Protein beta Subunits; 0/GTP-Binding Protein gamma Subunits; 0/Proto-Oncogene Proteins c-fos; 0/Transcription Factor AP-1

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