This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lewis-Tuffin, L. J.
Right arrow Articles by Cidlowski, J. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lewis-Tuffin, L. J.
Right arrow Articles by Cidlowski, J. A.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, March 2007, p. 2266-2282, Vol. 27, No. 6
0270-7306/07/$08.00+0     doi:10.1128/MCB.01439-06

Human Glucocorticoid Receptor ß Binds RU-486 and Is Transcriptionally Active{triangledown}

Laura J. Lewis-Tuffin,1,{dagger} Christine M. Jewell,1 Rachelle J. Bienstock,2 Jennifer B. Collins,3 and John A. Cidlowski1*

Laboratory of Signal Transduction,1 Scientific Computing Laboratory,2 NIEHS Microarray Facility, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, 111 TW Alexander Drive, Research Triangle Park, North Carolina 277093

Received 4 August 2006/ Returned for modification 1 September 2006/ Accepted 5 January 2007

Human glucocorticoid receptor (hGR) is expressed as two alternately spliced C-terminal isoforms, {alpha} and ß. In contrast to the canonical hGR{alpha}, hGRß is a nucleus-localized orphan receptor thought not to bind ligand and not to affect gene transcription other than by acting as a dominant negative to hGR{alpha}. Here we used confocal microscopy to examine the cellular localization of transiently expressed fluorescent protein-tagged hGRß in COS-1 and U-2 OS cells. Surprisingly, yellow fluorescent protein (YFP)-hGRß was predominantly located in the cytoplasm and translocated to the nucleus following application of the glucocorticoid antagonist RU-486. This effect of RU-486 was confirmed with transiently expressed wild-type hGRß. Confocal microscopy of coexpressed YFP-hGRß and cyan fluorescent protein-hGR{alpha} in COS-1 cells indicated that the receptors move into the nucleus independently. Using a ligand binding assay, we confirmed that hGRß bound RU-486 but not the hGR{alpha} ligand dexamethasone. Examination of the cellular localization of YFP-hGRß in response to a series of 57 related compounds indicated that RU-486 is thus far the only identified ligand that interacts with hGRß. The selective interaction of RU-486 with hGRß was also supported by molecular modeling and computational docking studies. Interestingly, microarray analysis indicates that hGRß, expressed in the absence of hGR{alpha}, can regulate gene expression and furthermore that occupation of hGRß with the antagonist RU-486 diminishes that capacity despite the lack of helix 12 in the ligand binding domain.

* Corresponding author. Mailing address: National Institute of Environmental Health Sciences, P.O. Box 12233, MD F3-07, Research Triangle Park, NC 27709. Phone: (919) 541-1564. Fax: (919) 541-1367. E-mail: cidlows1{at}niehs.nih.gov.

{triangledown} Published ahead of print on 22 January 2007.

{dagger} Present address: Department of Cancer Biology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224.

Molecular and Cellular Biology, March 2007, p. 2266-2282, Vol. 27, No. 6
0270-7306/07/$08.00+0     doi:10.1128/MCB.01439-06




This article has been cited by other articles:

  • Hofbauer, L. C., Rauner, M. (2009). Minireview: Live and Let Die: Molecular Effects of Glucocorticoids on Bone Cells. Mol. Endocrinol. 23: 1525-1531 [Abstract] [Full Text]  
  • Marik, P. E. (2009). Critical Illness-Related Corticosteroid Insufficiency. Chest 135: 181-193 [Abstract] [Full Text]  
  • Schaaf, M. J. M., Champagne, D., van Laanen, I. H. C., van Wijk, D. C. W. A., Meijer, A. H., Meijer, O. C., Spaink, H. P., Richardson, M. K. (2008). Discovery of a Functional Glucocorticoid Receptor {beta}-Isoform in Zebrafish. Endocrinology 149: 1591-1599 [Abstract] [Full Text]  
  • Zhang, X., Clark, A. F., Yorio, T. (2008). FK506-Binding Protein 51 Regulates Nuclear Transport of the Glucocorticoid Receptor {beta} and Glucocorticoid Responsiveness. IOVS 49: 1037-1047 [Abstract] [Full Text]  
  • Kumamaru, E., Numakawa, T., Adachi, N., Yagasaki, Y., Izumi, A., Niyaz, M., Kudo, M., Kunugi, H. (2008). Glucocorticoid Prevents Brain-Derived Neurotrophic Factor-Mediated Maturation of Synaptic Function in Developing Hippocampal Neurons through Reduction in the Activity of Mitogen-Activated Protein Kinase. Mol. Endocrinol. 22: 546-558 [Abstract] [Full Text]  
  • Das, S., Schapira, M., Tomic-Canic, M., Goyanka, R., Cardozo, T., Samuels, H. H. (2007). Farnesyl Pyrophosphate Is a Novel Transcriptional Activator for a Subset of Nuclear Hormone Receptors. Mol. Endocrinol. 21: 2672-2686 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»