Source:http://linkedlifedata.com/resource/pubmed/id/16799563
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
7103
|
| pubmed:dateCreated |
2006-8-10
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| pubmed:databankReference | |
| pubmed:abstractText |
The sterol regulatory element binding protein (SREBP) family of transcription activators are critical regulators of cholesterol and fatty acid homeostasis. We previously demonstrated that human SREBPs bind the CREB-binding protein (CBP)/p300 acetyltransferase KIX domain and recruit activator-recruited co-factor (ARC)/Mediator co-activator complexes through unknown mechanisms. Here we show that SREBPs use the evolutionarily conserved ARC105 (also called MED15) subunit to activate target genes. Structural analysis of the SREBP-binding domain in ARC105 by NMR revealed a three-helix bundle with marked similarity to the CBP/p300 KIX domain. In contrast to SREBPs, the CREB and c-Myb activators do not bind the ARC105 KIX domain, although they interact with the CBP KIX domain, revealing a surprising specificity among structurally related activator-binding domains. The Caenorhabditis elegans SREBP homologue SBP-1 promotes fatty acid homeostasis by regulating the expression of lipogenic enzymes. We found that, like SBP-1, the C. elegans ARC105 homologue MDT-15 is required for fatty acid homeostasis, and show that both SBP-1 and MDT-15 control transcription of genes governing desaturation of stearic acid to oleic acid. Notably, dietary addition of oleic acid significantly rescued various defects of nematodes targeted with RNA interference against sbp-1 and mdt-15, including impaired intestinal fat storage, infertility, decreased size and slow locomotion, suggesting that regulation of oleic acid levels represents a physiologically critical function of SBP-1 and MDT-15. Taken together, our findings demonstrate that ARC105 is a key effector of SREBP-dependent gene regulation and control of lipid homeostasis in metazoans.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Caenorhabditis elegans Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol,
http://linkedlifedata.com/resource/pubmed/chemical/MED15 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Mediator Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Sterol Regulatory Element Binding...,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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| pubmed:status |
MEDLINE
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| pubmed:month |
Aug
|
| pubmed:issn |
1476-4687
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| pubmed:author |
pubmed-author:DeBeaumontRosalieR,
pubmed-author:HartAnne CAC,
pubmed-author:HybertsSven GSG,
pubmed-author:IyerLakshmananL,
pubmed-author:Jim SunZ-YZY,
pubmed-author:MacolChristineC,
pubmed-author:NäärAnders MAM,
pubmed-author:SaitoR MakoRM,
pubmed-author:SatterleeJohn SJS,
pubmed-author:TjianRobertR,
pubmed-author:VoughtBryan WBW,
pubmed-author:WagnerGerhardG,
pubmed-author:WalkerAmy KAK,
pubmed-author:WattsJennifer LJL,
pubmed-author:YangFajunF,
pubmed-author:YangShaosongS,
pubmed-author:van den HeuvelSanderS
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| pubmed:issnType |
Electronic
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| pubmed:day |
10
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| pubmed:volume |
442
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
700-4
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| pubmed:dateRevised |
2011-8-1
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| pubmed:meshHeading |
pubmed-meshheading:16799563-Amino Acid Sequence,
pubmed-meshheading:16799563-Animals,
pubmed-meshheading:16799563-Caenorhabditis elegans,
pubmed-meshheading:16799563-Caenorhabditis elegans Proteins,
pubmed-meshheading:16799563-Cholesterol,
pubmed-meshheading:16799563-Homeostasis,
pubmed-meshheading:16799563-Humans,
pubmed-meshheading:16799563-Lipid Metabolism,
pubmed-meshheading:16799563-Mediator Complex,
pubmed-meshheading:16799563-Mice,
pubmed-meshheading:16799563-Models, Molecular,
pubmed-meshheading:16799563-Molecular Sequence Data,
pubmed-meshheading:16799563-Nuclear Magnetic Resonance, Biomolecular,
pubmed-meshheading:16799563-Protein Binding,
pubmed-meshheading:16799563-Protein Structure, Tertiary,
pubmed-meshheading:16799563-Sterol Regulatory Element Binding Proteins,
pubmed-meshheading:16799563-Transcription Factors,
pubmed-meshheading:16799563-Transcriptional Activation
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| pubmed:year |
2006
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| pubmed:articleTitle |
An ARC/Mediator subunit required for SREBP control of cholesterol and lipid homeostasis.
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| pubmed:affiliation |
Massachusetts General Hospital Cancer Center, Building 149, 13th Street, Charlestown, Massachusetts 02129, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|