Document Detail

Human estrogen receptor transactivational capacity is determined by both cellular and promoter context and mediated by two functionally distinct intramolecular regions.
MedLine Citation:
PMID:  8152428     Owner:  NLM     Status:  MEDLINE    
We have used a series of human estrogen receptor (ER) mutants to evaluate the cell- and promoter-specific transcriptional activities of the TAF1 and TAF2 transactivation regions within the human ER. We show that the manifestation of TAF1 or TAF2 function depends strongly upon promoter context; on certain promoters, both the TAF1 and TAF2 activators are required for wild-type transcriptional activity, whereas on other promoters, the TAF1 and TAF2 activators function independently. Using these constructs, we show that the antagonist activity of the triphenylethylene-derived antiestrogens, e.g. tamoxifen, arises from their intrinsic inability to activate ER TAF2 function. However, on certain promoters, these antiestrogens efficiently activate gene transcription through ER. Consistent with this observation, the TAF2 function of the ER is not required on all promoters. In these TAF2-independent promoter contexts, TAF2 function may be provided by a separate transcription factor bound to the promoter. These data suggest that 1) TAF1 may be the major transcriptional activator of the ER; and 2) TAF2 functions as a transcriptional facilitator. On promoters where TAF2 function is provided independently of the ER, the TAF1 function of the ER can function independently of TAF2 activity, allowing triphenylethylene-derived antiestrogens to demonstrate partial agonist activity. These observations provide a possible molecular explanation for the tissue-specific partial agonist properties of tamoxifen and related triphenylethylene antiestrogens observed in vivo.
M T Tzukerman; A Esty; D Santiso-Mere; P Danielian; M G Parker; R B Stein; J W Pike; D P McDonnell
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Molecular endocrinology (Baltimore, Md.)     Volume:  8     ISSN:  0888-8809     ISO Abbreviation:  Mol. Endocrinol.     Publication Date:  1994 Jan 
Date Detail:
Created Date:  1994-05-09     Completed Date:  1994-05-09     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8801431     Medline TA:  Mol Endocrinol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  21-30     Citation Subset:  IM    
Department of Molecular Biology, Ligand Pharmaceuticals, Inc., San Diego, California 92121.
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MeSH Terms
Binding, Competitive
Cell Line
Complement C3 / pharmacology
Promoter Regions, Genetic*
Receptors, Estrogen / chemistry,  genetics,  physiology*
Recombinant Proteins / metabolism
Tamoxifen / pharmacology
Transcription, Genetic / drug effects
Transcriptional Activation*
Reg. No./Substance:
0/Complement C3; 0/Receptors, Estrogen; 0/Recombinant Proteins; 10540-29-1/Tamoxifen

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