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Mol Cell Biol. 2007 Apr;27(7):2442-51. Epub 2007 Jan 29.

The ligand binding domain controls glucocorticoid receptor dynamics independent of ligand release.

Author information

1
Department of Cellular and Molecular Pharmacology, University of California-San Francisco, 600 16th Street, Room GH-S574, San Francisco, CA 94107-2280, USA.

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 co-chaperone 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.

PMID:
17261597
PMCID:
PMC1899895
DOI:
10.1128/MCB.01570-06
[Indexed for MEDLINE]
Free PMC Article

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