HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Haché, R. J. G. Articles by Lefebvre, Y. A. Search for Related Content PubMed PubMed Citation Articles by Haché, R. J. G. Articles by Lefebvre, Y. A.

J Biol Chem, Vol. 274, Issue 3, 1432-1439, January 15, 1999

Nucleocytoplasmic Trafficking of Steroid-free Glucocorticoid Receptor

Robert J. G. Haché^§, Raymond Tse, Terry Reich, Joanne G. A. Savory^¶, and Yvonne A. Lefebvre^§

From the Departments of  Medicine and ^§ Biochemistry, Microbiology, and Immunology and the ^¶ Graduate Program in Biochemistry, University of Ottawa, The Loeb Health Research Institute at the Ottawa Hospital, Ottawa, Ontario K1Y 4E9, Canada

Glucocorticoid receptor (GR) recycles between an inactive form complexed with heat shock proteins (hsps) and localized to the cytoplasm and a free liganded form that regulates specific gene transcription in the nucleus. We report here that, contrary to previous assumptions, association of GR into hsp-containing complexes is not sufficient to prevent the shuttling or trafficking of the GR across the nuclear membrane. Following the withdrawal of treatment with cortisol or the hormone antagonist RU486, GRs recycled rapidly into hsp-associated, hormone-responsive complexes. However, cortisol-withdrawn receptors redistributed to the cytoplasm very slowly (t_1/2 = 8-9 h) and RU486-withdrawn receptors not at all. Persistent localization of these GRs to the nucleus was not due to a gross defect in export, since in both instances the complexed nuclear GRs transferred efficiently between heterokaryon nuclei. Moreover, the addition of a nuclear retention signal to the N terminus of GR induced the transfer of naive receptor to the nucleus in the absence of steroid. These results suggest that the localization of GR to the cytoplasm is determined by fine control of the rates of transfer of GR across the nuclear membrane and/or by active retention that occurs independently from the association of GR with hsps.

---

Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

This article has been cited by other articles:

				A. Carrigan, R. F. Walther, H. A. Salem, D. Wu, E. Atlas, Y. A. Lefebvre, and R. J. G. Hache An Active Nuclear Retention Signal in the Glucocorticoid Receptor Functions as a Strong Inducer of Transcriptional Activation J. Biol. Chem., April 13, 2007; 282(15): 10963 - 10971. [Abstract] [Full Text] [PDF]

				R. Shao, E. Egecioglu, B. Weijdegard, K. Ljungstrom, C. Ling, J. Fernandez-Rodriguez, and H. Billig Developmental and hormonal regulation of progesterone receptor A-form expression in female mouse lung in vivo: interaction with glucocorticoid receptors. J. Endocrinol., September 1, 2006; 190(3): 857 - 870. [Abstract] [Full Text] [PDF]

				J. Ouyang, T. Jiang, M. Tan, Y. Cui, and X. Li Abnormal Expression and Distribution of Heat Shock Protein 90: Potential Etiologic Immunoendocrine Mechanism of Glucocorticoid Resistance in Idiopathic Nephrotic Syndrome Clin. Vaccine Immunol., April 1, 2006; 13(4): 496 - 500. [Abstract] [Full Text] [PDF]

				J. P. DeLany, Z. E. Floyd, S. Zvonic, A. Smith, A. Gravois, E. Reiners, X. Wu, G. Kilroy, M. Lefevre, and J. M. Gimble Proteomic Analysis of Primary Cultures of Human Adipose-derived Stem Cells: Modulation by Adipogenesis Mol. Cell. Proteomics, June 1, 2005; 4(6): 731 - 740. [Abstract] [Full Text] [PDF]

				R. F. Walther, E. Atlas, A. Carrigan, Y. Rouleau, A. Edgecombe, L. Visentin, C. Lamprecht, G. C. Addicks, R. J. G. Hache, and Y. A. Lefebvre A Serine/Threonine-rich Motif Is One of Three Nuclear Localization Signals That Determine Unidirectional Transport of the Mineralocorticoid Receptor to the Nucleus J. Biol. Chem., April 29, 2005; 280(17): 17549 - 17561. [Abstract] [Full Text] [PDF]

				X.-F. Lin, B.-X. Zhao, H.-Z. Chen, X.-F. Ye, C.-Y. Yang, H.-Y. Zhou, M.-Q. Zhang, S.-C. Lin, and Q. Wu RXR{alpha} acts as a carrier for TR3 nuclear export in a 9-cis retinoic acid-dependent manner in gastric cancer cells J. Cell Sci., November 1, 2004; 117(23): 5609 - 5621. [Abstract] [Full Text] [PDF]

				H. C. Whitaker, S. Hanrahan, N. Totty, S. C. Gamble, J. Waxman, A. C. B. Cato, H. C. Hurst, and C. L. Bevan Androgen Receptor Is Targeted to Distinct Subcellular Compartments in Response to Different Therapeutic Antiandrogens Clin. Cancer Res., November 1, 2004; 10(21): 7392 - 7401. [Abstract] [Full Text] [PDF]

				P. Sartorato, F. Cluzeaud, J. Fagart, S. Viengchareun, M. Lombes, and M.-C. Zennaro New Naturally Occurring Missense Mutations of the Human Mineralocorticoid Receptor Disclose Important Residues Involved in Dynamic Interactions with Deoxyribonucleic Acid, Intracellular Trafficking, and Ligand Binding Mol. Endocrinol., September 1, 2004; 18(9): 2151 - 2165. [Abstract] [Full Text] [PDF]

				N. D. Freedman and K. R. Yamamoto Importin 7 and Importin {alpha}/Importin {beta} Are Nuclear Import Receptors for the Glucocorticoid Receptor Mol. Biol. Cell, May 1, 2004; 15(5): 2276 - 2286. [Abstract] [Full Text] [PDF]

				J. Botos, W. Xian, D. F. Smith, and C. L. Smith Progesterone Receptor Deficient in Chromatin Binding Has an Altered Cellular State J. Biol. Chem., April 9, 2004; 279(15): 15231 - 15239. [Abstract] [Full Text] [PDF]

				R. F. Walther, C. Lamprecht, A. Ridsdale, I. Groulx, S. Lee, Y. A. Lefebvre, and R. J. G. Hache Nuclear Export of the Glucocorticoid Receptor Is Accelerated by Cell Fusion-dependent Release of Calreticulin J. Biol. Chem., September 26, 2003; 278(39): 37858 - 37864. [Abstract] [Full Text] [PDF]

				T. Kino, E. Souvatzoglou, M. U. De Martino, M. Tsopanomihalu, Y. Wan, and G. P. Chrousos Protein 14-3-3{sigma} Interacts with and Favors Cytoplasmic Subcellular Localization of the Glucocorticoid Receptor, Acting as a Negative Regulator of the Glucocorticoid Signaling Pathway J. Biol. Chem., July 3, 2003; 278(28): 25651 - 25656. [Abstract] [Full Text] [PDF]

				E. A. Komarova, N. Neznanov, P. G. Komarov, M. V. Chernov, K. Wang, and A. V. Gudkov p53 Inhibitor Pifithrin alpha Can Suppress Heat Shock and Glucocorticoid Signaling Pathways J. Biol. Chem., April 25, 2003; 278(18): 15465 - 15468. [Abstract] [Full Text] [PDF]

				P. Maruvada, C. T. Baumann, G. L. Hager, and P. M. Yen Dynamic Shuttling and Intranuclear Mobility of Nuclear Hormone Receptors J. Biol. Chem., March 28, 2003; 278(14): 12425 - 12432. [Abstract] [Full Text] [PDF]

				M. Itoh, M. Adachi, H. Yasui, M. Takekawa, H. Tanaka, and K. Imai Nuclear Export of Glucocorticoid Receptor is Enhanced by c-Jun N-Terminal Kinase-Mediated Phosphorylation Mol. Endocrinol., October 1, 2002; 16(10): 2382 - 2392. [Abstract] [Full Text] [PDF]

				M. S. Qutob, R. N. Bhattacharjee, E. Pollari, S. P. Yee, and J. Torchia Microtubule-Dependent Subcellular Redistribution of the Transcriptional Coactivator p/CIP Mol. Cell. Biol., September 15, 2002; 22(18): 6611 - 6626. [Abstract] [Full Text] [PDF]

				K. Prufer and J. Barsony Retinoid X Receptor Dominates the Nuclear Import and Export of the Unliganded Vitamin D Receptor Mol. Endocrinol., August 1, 2002; 16(8): 1738 - 1751. [Abstract] [Full Text] [PDF]

				D. J. Mulholland, H. Cheng, K. Reid, P. S. Rennie, and C. C. Nelson The Androgen Receptor Can Promote beta -Catenin Nuclear Translocation Independently of Adenomatous Polyposis Coli J. Biol. Chem., May 10, 2002; 277(20): 17933 - 17943. [Abstract] [Full Text] [PDF]

				J. G. A. Savory, G. G. Préfontaine, C. Lamprecht, M. Liao, R. F. Walther, Y. A. Lefebvre, and R. J. G. Haché Glucocorticoid Receptor Homodimers and Glucocorticoid-Mineralocorticoid Receptor Heterodimers Form in the Cytoplasm through Alternative Dimerization Interfaces Mol. Cell. Biol., February 1, 2001; 21(3): 781 - 793. [Abstract] [Full Text]

				Y. Wan, K. K. Coxe, V. G. Thackray, P. R. Housley, and S. K. Nordeen Separable Features of the Ligand-Binding Domain Determine the Differential Subcellular Localization and Ligand-Binding Specificity of Glucocorticoid Receptor and Progesterone Receptor Mol. Endocrinol., January 1, 2001; 15(1): 17 - 31. [Abstract] [Full Text]

				J Bertinato, C Schild-Poulter, and R. Hache Nuclear localization of Ku antigen is promoted independently by basic motifs in the Ku70 and Ku80 subunits J. Cell Sci., January 1, 2001; 114(1): 89 - 99. [Abstract] [PDF]

				H Poukka, U Karvonen, N Yoshikawa, H Tanaka, J. Palvimo, and O. Janne The RING finger protein SNURF modulates nuclear trafficking of the androgen receptor J. Cell Sci., January 9, 2000; 113(17): 2991 - 3001. [Abstract] [PDF]

				N Kikyo and A. Wolffe Reprogramming nuclei: insights from cloning, nuclear transfer and heterokaryons J. Cell Sci., January 1, 2000; 113(1): 11 - 20. [Abstract] [PDF]

				S. E. Heid, R. S. Pollenz, and H. I. Swanson Role of Heat Shock Protein 90 Dissociation in Mediating Agonist-Induced Activation of the Aryl Hydrocarbon Receptor Mol. Pharmacol., January 1, 2000; 57(1): 82 - 92. [Abstract] [Full Text]

				M. L. Lu, M. C. Schneider, Y. Zheng, X. Zhang, and J. P. Richie Caveolin-1 Interacts with Androgen Receptor. A POSITIVE MODULATOR OF ANDROGEN RECEPTOR MEDIATED TRANSACTIVATION J. Biol. Chem., April 13, 2001; 276(16): 13442 - 13451. [Abstract] [Full Text] [PDF]