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The Ligand Binding Domain Controls Glucocorticoid Receptor Dynamics Independent of Ligand Release

The Ligand Binding Domain Controls Glucocorticoid Receptor Dynamics Independent of Ligand Release The Ligand Binding Domain Controls Glucocorticoid Receptor Dynamics Independent of Ligand Release ▿ Sebastiaan H. Meijsing 1 , Cem Elbi 2 , † , Hans F. Luecke 1 , Gordon L. Hager 2 and Keith R. Yamamoto 1 , * 1 Department of Cellular and Molecular Pharmacology, University of California-San Francisco, San Francisco, California 94107 2 Laboratory of Receptor Biology and Gene Expression, National Institutes of Health, Bethesda, Maryland 20892 ABSTRACT Ligand binding to the glucocorticoid receptor (GR) results in receptor binding to glucocorticoid response elements (GREs) and the formation of transcriptional regulatory complexes. Equally important, these complexes are continuously disassembled, with active processes driving GR off GREs. We found that cochaperone p23-dependent disruption of GR-driven transcription depended on the ligand binding domain (LBD). Next, we examined the importance of the LBD and of ligand dissociation in GR-GRE dissociation in living cells. We showed in fluorescence recovery after photobleaching studies that dissociation of GR from GREs is faster in the absence of the LBD. Furthermore, GR interaction with a target promoter revealed ligand-specific exchange rates. However, using covalently binding ligands, we demonstrated that ligand dissociation is not required for receptor dissociation from GREs. Overall, these studies showed that activities impinging on the LBD regulate GR exchange with GREs but that the dissociation of GR from GREs is independent from ligand dissociation. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Molecular and Cellular Biology American Society For Microbiology

The Ligand Binding Domain Controls Glucocorticoid Receptor Dynamics Independent of Ligand Release

The Ligand Binding Domain Controls Glucocorticoid Receptor Dynamics Independent of Ligand Release

Molecular and Cellular Biology , Volume 27 (7): 2442 – Apr 1, 2007

Abstract

The Ligand Binding Domain Controls Glucocorticoid Receptor Dynamics Independent of Ligand Release ▿ Sebastiaan H. Meijsing 1 , Cem Elbi 2 , † , Hans F. Luecke 1 , Gordon L. Hager 2 and Keith R. Yamamoto 1 , * 1 Department of Cellular and Molecular Pharmacology, University of California-San Francisco, San Francisco, California 94107 2 Laboratory of Receptor Biology and Gene Expression, National Institutes of Health, Bethesda, Maryland 20892 ABSTRACT Ligand binding to the glucocorticoid receptor (GR) results in receptor binding to glucocorticoid response elements (GREs) and the formation of transcriptional regulatory complexes. Equally important, these complexes are continuously disassembled, with active processes driving GR off GREs. We found that cochaperone p23-dependent disruption of GR-driven transcription depended on the ligand binding domain (LBD). Next, we examined the importance of the LBD and of ligand dissociation in GR-GRE dissociation in living cells. We showed in fluorescence recovery after photobleaching studies that dissociation of GR from GREs is faster in the absence of the LBD. Furthermore, GR interaction with a target promoter revealed ligand-specific exchange rates. However, using covalently binding ligands, we demonstrated that ligand dissociation is not required for receptor dissociation from GREs. Overall, these studies showed that activities impinging on the LBD regulate GR exchange with GREs but that the dissociation of GR from GREs is independent from ligand dissociation.

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References (43)

Publisher
American Society For Microbiology
Copyright
Copyright © 2007 by the American society for Microbiology.
ISSN
0270-7306
eISSN
1098-5549
DOI
10.1128/MCB.01570-06
pmid
17261597
Publisher site
See Article on Publisher Site

Abstract

The Ligand Binding Domain Controls Glucocorticoid Receptor Dynamics Independent of Ligand Release ▿ Sebastiaan H. Meijsing 1 , Cem Elbi 2 , † , Hans F. Luecke 1 , Gordon L. Hager 2 and Keith R. Yamamoto 1 , * 1 Department of Cellular and Molecular Pharmacology, University of California-San Francisco, San Francisco, California 94107 2 Laboratory of Receptor Biology and Gene Expression, National Institutes of Health, Bethesda, Maryland 20892 ABSTRACT Ligand binding to the glucocorticoid receptor (GR) results in receptor binding to glucocorticoid response elements (GREs) and the formation of transcriptional regulatory complexes. Equally important, these complexes are continuously disassembled, with active processes driving GR off GREs. We found that cochaperone p23-dependent disruption of GR-driven transcription depended on the ligand binding domain (LBD). Next, we examined the importance of the LBD and of ligand dissociation in GR-GRE dissociation in living cells. We showed in fluorescence recovery after photobleaching studies that dissociation of GR from GREs is faster in the absence of the LBD. Furthermore, GR interaction with a target promoter revealed ligand-specific exchange rates. However, using covalently binding ligands, we demonstrated that ligand dissociation is not required for receptor dissociation from GREs. Overall, these studies showed that activities impinging on the LBD regulate GR exchange with GREs but that the dissociation of GR from GREs is independent from ligand dissociation.

Journal

Molecular and Cellular BiologyAmerican Society For Microbiology

Published: Apr 1, 2007

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