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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7334
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pubmed:dateCreated |
2011-2-18
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pubmed:abstractText |
Toll-like receptors (TLRs) function as initiators of inflammation through their ability to sense pathogen-associated molecular patterns and products of tissue damage. Transcriptional activation of many TLR-responsive genes requires an initial de-repression step in which nuclear receptor co-repressor (NCoR) complexes are actively removed from the promoters of target genes to relieve basal repression. Ligand-dependent SUMOylation of liver X receptors (LXRs) has been found to suppress TLR4-induced transcription potently by preventing the NCoR clearance step, but the underlying mechanisms remain enigmatic. Here we provide evidence that coronin 2A (CORO2A), a component of the NCoR complex of previously unknown function, mediates TLR-induced NCoR turnover by a mechanism involving interaction with oligomeric nuclear actin. SUMOylated LXRs block NCoR turnover by binding to a conserved SUMO2/SUMO3-interaction motif in CORO2A and preventing actin recruitment. Intriguingly, the LXR transrepression pathway can itself be inactivated by inflammatory signals that induce calcium/calmodulin-dependent protein kinase II? (CaMKII?)-dependent phosphorylation of LXRs, leading to their deSUMOylation by the SUMO protease SENP3 and release from CORO2A. These findings uncover a CORO2A-actin-dependent mechanism for the de-repression of inflammatory response genes that can be differentially regulated by phosphorylation and by nuclear receptor signalling pathways that control immunity and homeostasis.
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pubmed:grant |
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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/Actins,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Microfilament Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Orphan Nuclear Receptors,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Hydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/Senp3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Thioglycolates,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptors,
http://linkedlifedata.com/resource/pubmed/chemical/coronin proteins,
http://linkedlifedata.com/resource/pubmed/chemical/liver X receptor
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1476-4687
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pubmed:author |
pubmed-author:AouadiMyriamM,
pubmed-author:CzechMichael PMP,
pubmed-author:GandhiMeghalM,
pubmed-author:GhislettiSerenaS,
pubmed-author:GlassChristopher KCK,
pubmed-author:GoodeBruce LBL,
pubmed-author:HuangWendyW,
pubmed-author:RosenfeldMichael GMG,
pubmed-author:SaijoKaoruK,
pubmed-author:TeszGreg JGJ,
pubmed-author:YaoJoyeeJ,
pubmed-author:ZhangDawn XDX
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pubmed:issnType |
Electronic
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pubmed:day |
17
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pubmed:volume |
470
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
414-8
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pubmed:dateRevised |
2011-11-14
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pubmed:meshHeading |
pubmed-meshheading:21331046-Actins,
pubmed-meshheading:21331046-Animals,
pubmed-meshheading:21331046-Calcium-Calmodulin-Dependent Protein Kinase Type 2,
pubmed-meshheading:21331046-Cell Line,
pubmed-meshheading:21331046-Gene Expression Regulation,
pubmed-meshheading:21331046-Gene Knockdown Techniques,
pubmed-meshheading:21331046-HeLa Cells,
pubmed-meshheading:21331046-Homeostasis,
pubmed-meshheading:21331046-Humans,
pubmed-meshheading:21331046-Inflammation,
pubmed-meshheading:21331046-Lipopolysaccharides,
pubmed-meshheading:21331046-Mice,
pubmed-meshheading:21331046-Microfilament Proteins,
pubmed-meshheading:21331046-Orphan Nuclear Receptors,
pubmed-meshheading:21331046-Peptide Hydrolases,
pubmed-meshheading:21331046-Peritonitis,
pubmed-meshheading:21331046-Phosphorylation,
pubmed-meshheading:21331046-Promoter Regions, Genetic,
pubmed-meshheading:21331046-Protein Structure, Tertiary,
pubmed-meshheading:21331046-Signal Transduction,
pubmed-meshheading:21331046-Sumoylation,
pubmed-meshheading:21331046-Thioglycolates,
pubmed-meshheading:21331046-Toll-Like Receptors
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pubmed:year |
2011
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pubmed:articleTitle |
Coronin 2A mediates actin-dependent de-repression of inflammatory response genes.
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pubmed:affiliation |
Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0651, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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