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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2009-5-27
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pubmed:abstractText |
The nuclear receptor-type transcription factor retinoic acid receptor-related orphan receptor alpha (RORalpha) is a multifunctional molecule involved in tissue development and cellular function, such as inflammation, metabolism, and differentiation; however, the role of RORalpha during adipocyte differentiation has not yet been fully understood. Here we show that RORalpha inhibits the transcriptional activity of CCAAT/enhancer-binding protein beta (C/EBPbeta) without affecting its expression, thereby blocking the induction of both PPARgamma and C/EBPalpha, resulting in the suppression of C/EBPbeta-dependent adipogenesis. RORalpha interacted with C/EBPbeta so as to repress both the C/EBPbeta-p300 association and the C/EBPbeta-dependent recruitment of p300 to chromatin. In addition to the inhibitory effect on C/EBPbeta function, RORalpha also prevents the expression of the lipid droplet coating protein gene perilipin by peroxisome proliferators-activated receptor gamma (PPARgamma), acting through the specific mechanism of its promoter. We identified a suppressive ROR-responsive element overlapping the PPAR-responsive element in the perilipin promoter and verified that RORalpha competitively antagonizes the binding of PPARgamma. RORalpha inhibits PPARgamma-dependent adipogenesis along with the repression of perilipin induction. These findings suggest that RORalpha is a novel negative regulator of adipocyte differentiation that acts through dual mechanisms.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CCAAT-Enhancer-Binding Protein-beta,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Chromatin,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/E1A-Associated p300 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Ep300 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Receptor Subfamily 1...,
http://linkedlifedata.com/resource/pubmed/chemical/PPAR gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/perilipin 1
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1944-9917
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
23
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
759-71
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:19324970-3T3-L1 Cells,
pubmed-meshheading:19324970-Adipocytes,
pubmed-meshheading:19324970-Adipogenesis,
pubmed-meshheading:19324970-Animals,
pubmed-meshheading:19324970-CCAAT-Enhancer-Binding Protein-beta,
pubmed-meshheading:19324970-Carrier Proteins,
pubmed-meshheading:19324970-Cell Differentiation,
pubmed-meshheading:19324970-Chromatin,
pubmed-meshheading:19324970-DNA,
pubmed-meshheading:19324970-E1A-Associated p300 Protein,
pubmed-meshheading:19324970-Gene Expression Regulation,
pubmed-meshheading:19324970-Gene Knockdown Techniques,
pubmed-meshheading:19324970-Mice,
pubmed-meshheading:19324970-Nuclear Receptor Subfamily 1, Group F, Member 1,
pubmed-meshheading:19324970-PPAR gamma,
pubmed-meshheading:19324970-Phosphoproteins,
pubmed-meshheading:19324970-Phosphorylation,
pubmed-meshheading:19324970-Promoter Regions, Genetic,
pubmed-meshheading:19324970-Protein Binding,
pubmed-meshheading:19324970-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:19324970-Trans-Activators,
pubmed-meshheading:19324970-Transcription, Genetic
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pubmed:year |
2009
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pubmed:articleTitle |
The orphan nuclear receptor RORalpha restrains adipocyte differentiation through a reduction of C/EBPbeta activity and perilipin gene expression.
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pubmed:affiliation |
Department of Applied Biological Chemistry, The University of Tokyo, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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