Document Detail


Ligand-activated retinoic acid receptor inhibits AP-1 transactivation by disrupting c-Jun/c-Fos dimerization.
MedLine Citation:
PMID:  9973257     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In the presence of retinoic acid (RA), the retinoid receptors, retinoic acid receptor (RAR) and retinoid X receptor (RXR), are able to up-regulate transcription directly by binding to RA-responsive elements on the promoters of responsive genes. Liganded RARs and RXRs are also capable of down-regulating transcription, but, by contrast, this is an indirect effect, mediated by the interaction of these nuclear receptors not with DNA but the transcription factor activating protein-1 (AP-1). AP-1 is a dimeric complex of the protooncoproteins c-Jun and c-Fos and directly regulates transcription of genes important for cellular growth. Previous in vitro results have suggested that RARs can block AP-1 DNA binding. Using a mammalian two-hybrid system, we report here that human RARalpha (hRARalpha) can disrupt in a RA-dependent manner the homo- and heterodimerization properties of c-Jun and c-Fos. This inhibition of dimerization is cell specific, occurring only in those cells that exhibit RA-induced repression of AP-1 transcriptional activity. Furthermore, this mechanism appears to be specific for the RARs, since another potent inhibitor of AP-1 activity, the glucocorticoid receptor, does not affect AP-1 dimerization. Our data argue for a novel mechanism by which RARs can repress AP-1 DNA binding, in which liganded RARs are able to interfere with c-Jun/c-Jun homodimerization and c-Jun/c-Fos heterodimerization and, in this way, may prevent the formation of AP-1 complexes capable of DNA binding.
Authors:
X F Zhou; X Q Shen; L Shemshedini
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Molecular endocrinology (Baltimore, Md.)     Volume:  13     ISSN:  0888-8809     ISO Abbreviation:  Mol. Endocrinol.     Publication Date:  1999 Feb 
Date Detail:
Created Date:  1999-05-03     Completed Date:  1999-05-03     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8801431     Medline TA:  Mol Endocrinol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  276-85     Citation Subset:  IM    
Affiliation:
Department of Biology, University of Toledo, Ohio 43606, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
COS Cells
Cercopithecus aethiops
Chloramphenicol O-Acetyltransferase / analysis
Dimerization
Electrophoresis, Polyacrylamide Gel
Genes, fos / physiology*
Genes, jun / physiology*
Hela Cells
Humans
Ligands
Plasmids / chemistry
Receptors, Glucocorticoid / physiology
Receptors, Retinoic Acid / physiology*
Recombinant Fusion Proteins / physiology
Sensitivity and Specificity
Transcription Factor AP-1 / physiology*
Transfection
Grant Support
ID/Acronym/Agency:
DK-51274/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Ligands; 0/Receptors, Glucocorticoid; 0/Receptors, Retinoic Acid; 0/Recombinant Fusion Proteins; 0/Transcription Factor AP-1; EC 2.3.1.28/Chloramphenicol O-Acetyltransferase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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