Source:http://linkedlifedata.com/resource/pubmed/id/11514059
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
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| pubmed:dateCreated |
2001-8-21
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| pubmed:abstractText |
Estrogen-induced signaling mediated by estrogen receptors (ERs) is also affected by aberrant ERs that act as constitutively active or dominant negative modulators. Variant ERs can contribute to carcinogenesis and to the loss of estrogen responsiveness, rendering antiestrogen therapy ineffective. Determining target gene response during co-synthesis of different ER species is difficult, because dimers formed in the presence of more than one ER species are a heterogenous population of homo- or heterodimers. We engineered a homofusion ERalpha as a prototype single-chain receptor by genetically conjugating two ER monomers into a covalently fused single-chain protein to obtain a homogeneous population. This permits analysis of symmetrical or asymmetrical mutations that simulate variant homo- and heterodimers. Although a monomer, the homofusion receptor exhibited similar biochemical and functional properties to the dimeric ERalpha. We used activation function-2 (AF2) defective mutants as a model in either one or both receptor domains for a dominant-negative phenotype by suppressing the reporter activity induced by the WT receptor. When co-expressed with ERalpha, the fusion variant deficient in both AF2 functions suppressed the reporter activity effectively induced by ERalpha. These results show the utility of fusion receptors as models for generation of receptor-based agonists and antagonists.
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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/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Estrogen,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins
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| pubmed:status |
MEDLINE
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| pubmed:month |
Sep
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| pubmed:issn |
0303-7207
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
182
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
249-63
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:11514059-Animals,
pubmed-meshheading:11514059-Base Sequence,
pubmed-meshheading:11514059-Blotting, Western,
pubmed-meshheading:11514059-CHO Cells,
pubmed-meshheading:11514059-COS Cells,
pubmed-meshheading:11514059-Cricetinae,
pubmed-meshheading:11514059-DNA,
pubmed-meshheading:11514059-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:11514059-Escherichia coli,
pubmed-meshheading:11514059-Gene Expression Regulation,
pubmed-meshheading:11514059-Genes, Dominant,
pubmed-meshheading:11514059-HeLa Cells,
pubmed-meshheading:11514059-Humans,
pubmed-meshheading:11514059-Ligands,
pubmed-meshheading:11514059-Luciferases,
pubmed-meshheading:11514059-Mutation,
pubmed-meshheading:11514059-Protein Binding,
pubmed-meshheading:11514059-Receptors, Estrogen,
pubmed-meshheading:11514059-Recombinant Fusion Proteins
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| pubmed:year |
2001
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| pubmed:articleTitle |
Fusion estrogen receptor proteins: toward the development of receptor-based agonists and antagonists.
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| pubmed:affiliation |
Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY 14642, USA. mesut_muyan@urmc.rochester.edu
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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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