Document Detail


The ligand-mediated nuclear mobility and interaction with estrogen-responsive elements of estrogen receptors are subtype specific.
MedLine Citation:
PMID:  23014840     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
17β-Estradiol (E(2)) plays important roles in functions of many tissues. E(2) effects are mediated by estrogen receptor (ER) α and β. ERs regulate transcriptions through estrogen-responsive element (ERE)-dependent and ERE-independent modes of action. ER binding to ERE constitutes the basis of the ERE-dependent pathway. Direct/indirect ER interactions with transcription complexes define ERE-independent signaling. ERs share functional features. Ligand-bound ERs nevertheless induce distinct transcription profiles. Live cell imaging indicates a dynamic nature of gene expressions by highly mobile ERs. However, the relative contribution of ER mobility at the ERE-independent pathway to the overall kinetics of ER mobility remains undefined. We used fluorescent recovery after a photo-bleaching approach to assess the ligand-mediated mobilities of ERE binding-defective ERs, ER(EBD). The decrease in ERα mobility with E(2) or the selective ER modulator 4-hydroxyl-tamoxifen (4HT) was largely due to the interaction of the receptor with ERE. Thus, ERα bound to E(2) or 4HT mediates transcriptions from the ERE-independent pathway with remarkably fast kinetics that contributes fractionally to the overall motility of the receptor. The antagonist Imperial Chemical Industries 182 780 immobilized ERαs. The mobilities of ERβ and ERβ(EBD) in the presence of ligands were indistinguishable kinetically. Thus, ERβ mobility is independent of the nature of ligands and the mode of interaction with target sites. Chimeric ERs indicated that the carboxyl-termini are critical regions for subtype-specific mobility. Therefore, while ERs are highly mobile molecules interacting with target sites with fast kinetics, an indication of the hit-and-run model of transcription, they differ mechanistically to modulate transcriptions.
Authors:
Mesut Muyan; Linda M Callahan; Yanfang Huang; Andrew J Lee
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-10-30
Journal Detail:
Title:  Journal of molecular endocrinology     Volume:  49     ISSN:  1479-6813     ISO Abbreviation:  J. Mol. Endocrinol.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-10-31     Completed Date:  2013-03-14     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  8902617     Medline TA:  J Mol Endocrinol     Country:  England    
Other Details:
Languages:  eng     Pagination:  249-66     Citation Subset:  IM    
Affiliation:
Department of Biochemistry and Biophysics, University of Rochester Medical School, Rochester, New York 14642, USA. mesut_muyan@urmc.rochester.edu
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MeSH Terms
Descriptor/Qualifier:
Blotting, Western
Cell Line, Tumor
Cell Nucleus / metabolism*
Chromatin Immunoprecipitation
Electrophoretic Mobility Shift Assay
Green Fluorescent Proteins / genetics,  metabolism
HeLa Cells
Humans
Protein Binding
Protein Transport / genetics,  physiology
Receptors, Estrogen / genetics,  metabolism*
Response Elements / genetics*,  physiology
Grant Support
ID/Acronym/Agency:
CA113682/CA/NCI NIH HHS; R01 CA113682/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Receptors, Estrogen; 147336-22-9/Green Fluorescent Proteins
Comments/Corrections

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