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Molecular and Cellular Biology, February 2001, p. 781-793, Vol. 21, No. 3
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.3.781-793.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Glucocorticoid Receptor Homodimers and Glucocorticoid-Mineralocorticoid Receptor Heterodimers Form in the Cytoplasm through Alternative Dimerization Interfaces

Joanne G. A. Savory,1 Gratien G. Préfontaine,1 Claudia Lamprecht,2 Mingmin Liao,2 Rhian F. Walther,1 Yvonne A. Lefebvre,2,3,* and Robert J. G. Haché2,3

Departments of Medicine2 and Biochemistry, Microbiology & Immunology3 and Graduate Program in Biochemistry,1 The Loeb Health Research Institute at the Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada K1Y 4E9

Received 29 June 2000/Returned for modification 10 August 2000/Accepted 6 November 2000

Steroid hormone receptors act to regulate specific gene transcription primarily as steroid-specific dimers bound to palindromic DNA response elements. DNA-dependent dimerization contacts mediated between the receptor DNA binding domains stabilize DNA binding. Additionally, some steroid receptors dimerize prior to their arrival on DNA through interactions mediated through the receptor ligand binding domain. In this report, we describe the steroid-induced homomeric interaction of the rat glucocorticoid receptor (GR) in solution in vivo. Our results demonstrate that GR interacts in solution at least as a dimer, and we have delimited this interaction to a novel interface within the hinge region of GR that appears to be both necessary and sufficient for direct binding. Strikingly, we also demonstrate an interaction between GR and the mineralocorticoid receptor in solution in vivo that is dependent on the ligand binding domain of GR alone and is separable from homodimerization of the glucocorticoid receptor. These results indicate that functional interactions between the glucocorticoid and mineralocorticoid receptors in activating specific gene transcription are probably more complex than has been previously appreciated.

* Corresponding author. Mailing address: The Loeb Health Research Institute at the Ottawa Hospital, 725 Parkdale Ave., Ottawa, Ontario, Canada K1Y 4E9. Phone: (613) 761-5142. Fax: (613) 761-5036. E-mail: ylefebvre{at}ottawahospital.on.ca.

Molecular and Cellular Biology, February 2001, p. 781-793, Vol. 21, No. 3
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.3.781-793.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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