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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2005-4-5
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pubmed:databankReference |
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pubmed:abstractText |
The human nuclear receptor liver receptor homolog 1 (hLRH-1) plays an important role in the development of breast carcinomas. This orphan receptor is efficiently downregulated by the unusual co-repressor SHP and has been thought to be ligand-independent. We present the crystal structure at a resolution of 1.9 A of the ligand-binding domain of hLRH-1 in complex with the NR box 1 motif of human SHP, which we find contacts the AF-2 region of hLRH-1 using selective structural motifs. Electron density indicates phospholipid bound within the ligand-binding pocket, which we confirm using mass spectrometry of solvent-extracted samples. We further show that pocket mutations reduce phospholipid binding and receptor activity in vivo. Our results indicate that hLRH-1's control of gene expression is mediated by phospholipid binding, and establish hLRH-1 as a novel target for compounds designed to slow breast cancer development.
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pubmed:grant |
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pubmed:commentsCorrections |
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1545-9993
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pubmed:author |
pubmed-author:ChoiYunheeY,
pubmed-author:GuanZiqiangZ,
pubmed-author:HagerJanet MJM,
pubmed-author:LeeYoonkwangY,
pubmed-author:McDonnellDonald PDP,
pubmed-author:MooreDavid DDD,
pubmed-author:OrtlundEric AEA,
pubmed-author:RaetzChristian R HCR,
pubmed-author:RedinboMatthew RMR,
pubmed-author:SafiRachidR,
pubmed-author:SolomonIsaac HIH,
pubmed-author:TripathyAshutoshA
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pubmed:issnType |
Print
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pubmed:volume |
12
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
357-63
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pubmed:dateRevised |
2009-4-16
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pubmed:meshHeading |
pubmed-meshheading:15723037-Amino Acid Sequence,
pubmed-meshheading:15723037-Binding Sites,
pubmed-meshheading:15723037-Crystallography, X-Ray,
pubmed-meshheading:15723037-DNA-Binding Proteins,
pubmed-meshheading:15723037-Gene Expression Regulation,
pubmed-meshheading:15723037-HeLa Cells,
pubmed-meshheading:15723037-Humans,
pubmed-meshheading:15723037-Models, Molecular,
pubmed-meshheading:15723037-Molecular Sequence Data,
pubmed-meshheading:15723037-Phospholipids,
pubmed-meshheading:15723037-Protein Binding,
pubmed-meshheading:15723037-Protein Structure, Tertiary,
pubmed-meshheading:15723037-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:15723037-Sequence Alignment,
pubmed-meshheading:15723037-Spectrometry, Mass, Electrospray Ionization,
pubmed-meshheading:15723037-Transcription Factors
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pubmed:year |
2005
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pubmed:articleTitle |
Modulation of human nuclear receptor LRH-1 activity by phospholipids and SHP.
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pubmed:affiliation |
Department of Chemistry, Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, 27599, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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