The biology of the glucocorticoid receptor: New signaling mechanisms in health and disease

Journal of Allergy and Clinical Immunology

Volumn 132, Issue 5, 2013, Pages 1033-1044

  Oakley, Robert H ^a   Cidlowski, John A ^a  

^a NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES   (United States)

Author keywords

glucocorticoid; Glucocorticoid receptor; glucocorticoid signaling; isoforms

Indexed keywords

BETA 2 ADRENERGIC RECEPTOR; BETA 2 ADRENERGIC RECEPTOR STIMULATING AGENT; BETA ARRESTIN 1; BETA ARRESTIN 2; CASEIN KINASE II; CORTICOTROPIN; CORTICOTROPIN RELEASING FACTOR; CORTISONE; CYCLIN DEPENDENT KINASE; GLUCOCORTICOID; GLUCOCORTICOID RECEPTOR; GLUCOCORTICOID RECEPTOR ALPHA; GLUCOCORTICOID RECEPTOR BETA; GLYCOGEN SYNTHASE KINASE 3BETA; HORMONE RECEPTOR STIMULATING AGENT; LIGAND; MIFEPRISTONE; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE P38 INHIBITOR; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; SELECTIVE GLUCOCORTICOID RECEPTOR STIMULATING AGENT; SUMO PROTEIN; TRANSCRIPTION FACTOR; UNCLASSIFIED DRUG;

ACETYLATION; ADRENAL CORTEX; ALTERNATIVE RNA SPLICING; ANTIINFLAMMATORY ACTIVITY; ARTICLE; ASTHMA; CAVEOLA; CIRCADIAN RHYTHM; CUSHING SYNDROME; DNA POLYMORPHISM; DNA RESPONSIVE ELEMENT; GENETIC TRANSCRIPTION; HORMONE RESISTANCE; HUMAN; HYPOTHALAMUS HYPOPHYSIS ADRENAL SYSTEM; NONHUMAN; NUCLEAR LOCALIZATION SIGNAL; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN PROCESSING; PROTEIN STRUCTURE; RNA TRANSLATION; SENSITIVITY AND SPECIFICITY; SEX DIFFERENCE; SIGNAL TRANSDUCTION; SPLICING DEFECT; STRESS;

EID: 84887016715     PISSN: 00916749     EISSN: 10976825     Source Type: Journal    
DOI: 10.1016/j.jaci.2013.09.007     Document Type: Review

References (128)

1. P.J. Barnes Anti-inflammatory actions of glucocorticoids: molecular mechanisms Clin Sci (Lond) 94 1998 557 572
2. R.M. Sapolsky, L.M. Romero, and A.U. Munck How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions Endocr Rev 21 2000 55 89
3. T. Rhen, and J.A. Cidlowski Antiinflammatory action of glucocorticoids - new mechanisms for old drugs N Engl J Med 353 2005 1711 1723
4. J.M. Busillo, and J.A. Cidlowski The five Rs of glucocorticoid action during inflammation: ready, reinforce, repress, resolve, and restore Trends Endocrinol Metab 24 2013 109 119
5. J.N. Miner, M.H. Hong, and A. Negro-Vilar New and improved glucocorticoid receptor ligands Expert Opin Investig Drugs 14 2005 1527 1545
6. R.M. Evans The steroid and thyroid hormone receptor superfamily Science 240 1988 889 895
7. J. Galon, D. Franchimont, N. Hiroi, G. Frey, A. Boettner, and M. Ehrhart-Bornstein Gene profiling reveals unknown enhancing and suppressive actions of glucocorticoids on immune cells FASEB J 16 2002 61 71
8. N.Z. Lu, J.B. Collins, S.F. Grissom, and J.A. Cidlowski Selective regulation of bone cell apoptosis by translational isoforms of the glucocorticoid receptor Mol Cell Biol 27 2007 7143 7160
9. R. Ren, R.H. Oakley, D. Cruz-Topete, and J.A. Cidlowski Dual role for glucocorticoids in cardiomyocyte hypertrophy and apoptosis Endocrinology 153 2012 5346 5360
10. T.J. Cole, J.A. Blendy, A.P. Monaghan, K. Krieglstein, W. Schmid, and A. Aguzzi Targeted disruption of the glucocorticoid receptor gene blocks adrenergic chromaffin cell development and severely retards lung maturation Genes Dev 9 1995 1608 1621
11. T. Kino, M.U. De Martino, E. Charmandari, M. Mirani, and G.P. Chrousos Tissue glucocorticoid resistance/hypersensitivity syndromes J Steroid Biochem Mol Biol 85 2003 457 467
12. S.W. Lamberts, A.T. Huizenga, P. de Lange, F.H. de Jong, and J.W. Koper Clinical aspects of glucocorticoid sensitivity Steroids 61 1996 157 160
13. R. Gorovits, I. Ben-Dror, L.E. Fox, H.M. Westphal, and L. Vardimon Developmental changes in the expression and compartmentalization of the glucocorticoid receptor in embryonic retina Proc Natl Acad Sci U S A 91 1994 4786 4790
14. S.C. Hsu, and D.B. DeFranco Selectivity of cell cycle regulation of glucocorticoid receptor function J Biol Chem 270 1995 3359 3364
15. N.Z. Lu, and J.A. Cidlowski Translational regulatory mechanisms generate N-terminal glucocorticoid receptor isoforms with unique transcriptional target genes Mol Cell 18 2005 331 342
16. R.H. Oakley, and J.A. Cidlowski Cellular processing of the glucocorticoid receptor gene and protein: new mechanisms for generating tissue-specific actions of glucocorticoids J Biol Chem 286 2011 3177 3184
17. R. Kumar, and E.B. Thompson Gene regulation by the glucocorticoid receptor: structure:function relationship J Steroid Biochem Mol Biol 94 2005 383 394
18. R.K. Bledsoe, V.G. Montana, T.B. Stanley, C.J. Delves, C.J. Apolito, and D.D. McKee Crystal structure of the glucocorticoid receptor ligand binding domain reveals a novel mode of receptor dimerization and coactivator recognition Cell 110 2002 93 105
19. I. Grad, and D. Picard The glucocorticoid responses are shaped by molecular chaperones Mol Cell Endocrinol 275 2007 2 12
20. W.B. Pratt, and D.O. Toft Steroid receptor interactions with heat shock protein and immunophilin chaperones Endocr Rev 18 1997 306 360
21. J.R. Seckl 11beta-hydroxysteroid dehydrogenases: changing glucocorticoid action Curr Opin Pharmacol 4 2004 597 602
22. H. Yang, W. Dou, J. Lou, Y. Leng, and J. Shen Discovery of novel inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 by docking and pharmacophore modeling Bioorg Med Chem Lett 18 2008 1340 1345
23. M. Beato Gene regulation by steroid hormones Cell 56 1989 335 344
24. L.P. Freedman Anatomy of the steroid receptor zinc finger region Endocr Rev 13 1992 129 145
25. N.H. Uhlenhaut, G.D. Barish, R.T. Yu, M. Downes, M. Karunasiri, and C. Liddle Insights into negative regulation by the glucocorticoid receptor from genome-wide profiling of inflammatory cistromes Mol Cell 49 2013 158 171
26. M. Surjit, K.P. Ganti, A. Mukherji, T. Ye, G. Hua, and D. Metzger Widespread negative response elements mediate direct repression by agonist-liganded glucocorticoid receptor Cell 145 2011 224 241
27. W.H. Hudson, C. Youn, and E.A. Ortlund The structural basis of direct glucocorticoid-mediated transrepression Nat Struct Mol Biol 20 2013 53 58
28. S. John, P.J. Sabo, R.E. Thurman, M.H. Sung, S.C. Biddie, and T.A. Johnson Chromatin accessibility pre-determines glucocorticoid receptor binding patterns Nat Genet 43 2011 264 268
29. T.E. Reddy, J. Gertz, G.E. Crawford, M.J. Garabedian, and R.M. Myers The hypersensitive glucocorticoid response specifically regulates period 1 and expression of circadian genes Mol Cell Biol 32 2012 3756 3767
30. C.J. Burd, and T.K. Archer Chromatin architecture defines the glucocorticoid response Mol Cell Endocrinol 2013 [Epub ahead of print]
31. R.H. Oakley, J. Revollo, and J.A. Cidlowski Glucocorticoids regulate arrestin gene expression and redirect the signaling profile of G protein-coupled receptors Proc Natl Acad Sci U S A 109 2012 17591 17596
32. S. Ramamoorthy, and J.A. Cidlowski Ligand-induced repression of the glucocorticoid receptor gene is mediated by an NCoR1 repression complex formed by long-range chromatin interactions with intragenic glucocorticoid response elements Mol Cell Biol 33 2013 1711 1722
33. J.G. McNally, W.G. Muller, D. Walker, R. Wolford, and G.L. Hager The glucocorticoid receptor: rapid exchange with regulatory sites in living cells Science 287 2000 1262 1265
34. B.D. Jenkins, C.B. Pullen, and B.D. Darimont Novel glucocorticoid receptor coactivator effector mechanisms Trends Endocrinol Metab 12 2001 122 126
35. D.M. Lonard, and B.W. O'Malley Expanding functional diversity of the coactivators Trends Biochem Sci 30 2005 126 132
36. M.G. Rosenfeld, and C.K. Glass Coregulator codes of transcriptional regulation by nuclear receptors J Biol Chem 276 2001 36865 36868
37. S.H. Meijsing, M.A. Pufall, A.Y. So, D.L. Bates, L. Chen, and K.R. Yamamoto DNA binding site sequence directs glucocorticoid receptor structure and activity Science 324 2009 407 410
38. K. Ronacher, K. Hadley, C. Avenant, E. Stubsrud, S.S. Simons Jr., and A. Louw Ligand-selective transactivation and transrepression via the glucocorticoid receptor: role of cofactor interaction Mol Cell Endocrinol 299 2009 219 231
39. I. Rogatsky, and L.B. Ivashkiv Glucocorticoid modulation of cytokine signaling Tissue Antigens 68 2006 1 12
40. R.M. Nissen, and K.R. Yamamoto The glucocorticoid receptor inhibits NFkappaB by interfering with serine-2 phosphorylation of the RNA polymerase II carboxy-terminal domain Genes Dev 14 2000 2314 2329
41. H.F. Yang-Yen, J.C. Chambard, Y.L. Sun, T. Smeal, T.J. Schmidt, and J. Drouin Transcriptional interference between c-Jun and the glucocorticoid receptor: mutual inhibition of DNA binding due to direct protein-protein interaction Cell 62 1990 1205 1215
42. Y. Chinenov, R. Gupte, J. Dobrovolna, J.R. Flammer, B. Liu, and F.E. Michelassi Role of transcriptional coregulator GRIP1 in the anti-inflammatory actions of glucocorticoids Proc Natl Acad Sci U S A 109 2012 11776 11781
43. D. Duma, J.B. Collins, J.W. Chou, and J.A. Cidlowski Sexually dimorphic actions of glucocorticoids provide a link to inflammatory diseases with gender differences in prevalence Sci Signal 3 2010 ra74
44. F.L. Groeneweg, H. Karst, E.R. de Kloet, and M. Joels Mineralocorticoid and glucocorticoid receptors at the neuronal membrane, regulators of nongenomic corticosteroid signalling Mol Cell Endocrinol 350 2012 299 309
45. R.A. Samarasinghe, S.F. Witchell, and D.B. DeFranco Cooperativity and complementarity: synergies in non-classical and classical glucocorticoid signaling Cell Cycle 11 2012 2819 2827
46. J.D. Croxtall, Q. Choudhury, and R.J. Flower Glucocorticoids act within minutes to inhibit recruitment of signalling factors to activated EGF receptors through a receptor-dependent, transcription-independent mechanism Br J Pharmacol 130 2000 289 298
47. E. Solito, A. Mulla, J.F. Morris, H.C. Christian, R.J. Flower, and J.C. Buckingham Dexamethasone induces rapid serine-phosphorylation and membrane translocation of annexin 1 in a human folliculostellate cell line via a novel nongenomic mechanism involving the glucocorticoid receptor, protein kinase C, phosphatidylinositol 3-kinase, and mitogen-activated protein kinase Endocrinology 144 2003 1164 1174
48. L. Matthews, A. Berry, V. Ohanian, J. Ohanian, H. Garside, and D. Ray Caveolin mediates rapid glucocorticoid effects and couples glucocorticoid action to the antiproliferative program Mol Endocrinol 22 2008 1320 1330
49. R.A. Samarasinghe, R. Di Maio, D. Volonte, F. Galbiati, M. Lewis, and G. Romero Nongenomic glucocorticoid receptor action regulates gap junction intercellular communication and neural progenitor cell proliferation Proc Natl Acad Sci U S A 108 2011 16657 16662
50. K.L. Gross, and J.A. Cidlowski Tissue-specific glucocorticoid action: a family affair Trends Endocrinol Metab 19 9 2008 331 339
51. E.F. van Rossum, and S.W. Lamberts Polymorphisms in the glucocorticoid receptor gene and their associations with metabolic parameters and body composition Recent Prog Horm Res 59 2004 333 357
52. C.M. Jewell, and J.A. Cidlowski Molecular evidence for a link between the N363S glucocorticoid receptor polymorphism and altered gene expression J Clin Endocrinol Metab 92 2007 3268 3277
53. C.M. Bamberger, A.M. Bamberger, M. de Castro, and G.P. Chrousos Glucocorticoid receptor beta, a potential endogenous inhibitor of glucocorticoid action in humans J Clin Invest 95 1995 2435 2441
54. R.H. Oakley, M. Sar, and J.A. Cidlowski The human glucocorticoid receptor beta isoform. Expression, biochemical properties, and putative function J Biol Chem 271 1996 9550 9559
55. T. Kino, Y.A. Su, and G.P. Chrousos Human glucocorticoid receptor isoform beta: recent understanding of its potential implications in physiology and pathophysiology Cell Mol Life Sci 66 2009 3435 3448
56. L.J. Lewis-Tuffin, and J.A. Cidlowski The physiology of human glucocorticoid receptor beta (hGRbeta) and glucocorticoid resistance Ann N Y Acad Sci 1069 2006 1 9
57. P.J. Hauk, Q.A. Hamid, G.P. Chrousos, and D.Y. Leung Induction of corticosteroid insensitivity in human PBMCs by microbial superantigens J Allergy Clin Immunol 105 2000 782 787
58. O. Tliba, J.A. Cidlowski, and Y. Amrani CD38 expression is insensitive to steroid action in cells treated with tumor necrosis factor-alpha and interferon-gamma by a mechanism involving the up-regulation of the glucocorticoid receptor beta isoform Mol Pharmacol 69 2006 588 596
59. J.C. Webster, R.H. Oakley, C.M. Jewell, and J.A. Cidlowski Proinflammatory cytokines regulate human glucocorticoid receptor gene expression and lead to the accumulation of the dominant negative beta isoform: a mechanism for the generation of glucocorticoid resistance Proc Natl Acad Sci U S A 98 2001 6865 6870
60. L. Varricchio, E. Masselli, E. Alfani, A. Battistini, G. Migliaccio, and A.M. Vannucchi The dominant negative beta isoform of the glucocorticoid receptor is uniquely expressed in erythroid cells expanded from polycythemia vera patients Blood 118 2011 425 436
61. A. Jain, R.J. Wordinger, T. Yorio, and A.F. Clark Spliceosome protein (SRp) regulation of glucocorticoid receptor isoforms and glucocorticoid response in human trabecular meshwork cells Invest Ophthalmol Vis Sci 53 2012 857 866
62. Q. Xu, D.Y. Leung, and K.O. Kisich Serine-arginine-rich protein p30 directs alternative splicing of glucocorticoid receptor pre-mRNA to glucocorticoid receptor beta in neutrophils J Biol Chem 278 2003 27112 27118
63. J. Zhu, J.Y. Gong, O.B. Goodman Jr., L. Cartegni, D.M. Nanus, and R. Shen Bombesin attenuates pre-mRNA splicing of glucocorticoid receptor by regulating the expression of serine-arginine protein p30c (SRp30c) in prostate cancer cells Biochim Biophys Acta 1773 2007 1087 1094
64. R.H. Derijk, M.J. Schaaf, G. Turner, N.A. Datson, E. Vreugdenhil, and J. Cidlowski A human glucocorticoid receptor gene variant that increases the stability of the glucocorticoid receptor beta-isoform mRNA is associated with rheumatoid arthritis J Rheumatol 28 2001 2383 2388
65. M.J. Schaaf, and J.A. Cidlowski AUUUA motifs in the 3'UTR of human glucocorticoid receptor alpha and beta mRNA destabilize mRNA and decrease receptor protein expression Steroids 67 2002 627 636
66. J.J. Geelhoed, C. van Duijn, L. van Osch-Gevers, E.A. Steegers, A. Hofman, and W.A. Helbing Glucocorticoid receptor-9beta polymorphism is associated with systolic blood pressure and heart growth during early childhood. The Generation R Study Early Hum Dev 87 2011 97 102
67. C. Otte, S. Wust, S. Zhao, L. Pawlikowska, P.Y. Kwok, and M.A. Whooley Glucocorticoid receptor gene, low-grade inflammation, and heart failure: the Heart and Soul study J Clin Endocrinol Metab 95 2010 2885 2891
68. E.L. van den Akker, J.W. Koper, E.F. van Rossum, M.J. Dekker, H. Russcher, and F.H. de Jong Glucocorticoid receptor gene and risk of cardiovascular disease Arch Intern Med 168 2008 33 39
69. T. Kino, I. Manoli, S. Kelkar, Y. Wang, Y.A. Su, and G.P. Chrousos Glucocorticoid receptor (GR) beta has intrinsic, GRalpha-independent transcriptional activity Biochem Biophys Res Commun 381 2009 671 675
70. L.J. Lewis-Tuffin, C.M. Jewell, R.J. Bienstock, J.B. Collins, and J.A. Cidlowski The Human glucocorticoid receptor β (hGRβ) binds RU-486 and is transcriptionally active Mol Cell Biol 27 2007 2266 2282
71. A. Kelly, H. Bowen, Y.K. Jee, N. Mahfiche, C. Soh, and T. Lee The glucocorticoid receptor beta isoform can mediate transcriptional repression by recruiting histone deacetylases J Allergy Clin Immunol 121 2008 203 208.e1
72. S.H. Kim, D.H. Kim, P. Lavender, J.H. Seo, Y.S. Kim, and J.S. Park Repression of TNF-alpha-induced IL-8 expression by the glucocorticoid receptor-beta involves inhibition of histone H4 acetylation Exp Mol Med 41 2009 297 306
73. L.B. Li, D.Y. Leung, R.J. Martin, and E. Goleva Inhibition of histone deacetylase 2 expression by elevated glucocorticoid receptor beta in steroid-resistant asthma Am J Respir Crit Care Med 182 2010 877 883
74. D.C. DuBois, S. Sukumaran, W.J. Jusko, and R.R. Almon Evidence for a glucocorticoid receptor beta splice variant in the rat and its physiological regulation in liver Steroids 78 2013 312 320
75. T.D. Hinds Jr., S. Ramakrishnan, H.A. Cash, L.A. Stechschulte, G. Heinrich, and S.M. Najjar Discovery of glucocorticoid receptor-beta in mice with a role in metabolism Mol Endocrinol 24 2010 1715 1727
76. M.J. Schaaf, D. Champagne, I.H. van Laanen, D.C. van Wijk, A.H. Meijer, and O.C. Meijer Discovery of a functional glucocorticoid receptor beta-isoform in zebrafish Endocrinology 149 2008 1591 1599
77. D.W. Ray, J.R. Davis, A. White, and A.J. Clark Glucocorticoid receptor structure and function in glucocorticoid-resistant small cell lung carcinoma cells Cancer Res 56 1996 3276 3280
78. C. Beger, K. Gerdes, M. Lauten, W.J. Tissing, I. Fernandez-Munoz, and M. Schrappe Expression and structural analysis of glucocorticoid receptor isoform gamma in human leukaemia cells using an isoform-specific real-time polymerase chain reaction approach Br J Haematol 122 2003 245 252
79. C. Rivers, A. Levy, J. Hancock, S. Lightman, and M. Norman Insertion of an amino acid in the DNA-binding domain of the glucocorticoid receptor as a result of alternative splicing J Clin Endocrinol Metab 84 1999 4283 4286
80. P.A. Moalli, S. Pillay, N.L. Krett, and S.T. Rosen Alternatively spliced glucocorticoid receptor messenger RNAs in glucocorticoid-resistant human multiple myeloma cells Cancer Res 53 1993 3877 3879
81. P. de Lange, C.M. Segeren, J.W. Koper, E. Wiemer, P. Sonneveld, and A.O. Brinkmann Expression in hematological malignancies of a glucocorticoid receptor splice variant that augments glucocorticoid receptor-mediated effects in transfected cells Cancer Res 61 2001 3937 3941
82. D. Gaitan, C.R. DeBold, M.K. Turney, P. Zhou, D.N. Orth, and W.J. Kovacs Glucocorticoid receptor structure and function in an adrenocorticotropin- secreting small cell lung cancer Mol Endocrinol 9 1995 1193 1201
83. N.L. Krett, S. Pillay, P.A. Moalli, P.R. Greipp, and S.T. Rosen A variant glucocorticoid receptor messenger RNA is expressed in multiple myeloma patients Cancer Res 55 1995 2727 2729
84. M.R. Yudt, C.M. Jewell, R.J. Bienstock, and J.A. Cidlowski Molecular origins for the dominant negative function of human glucocorticoid receptor beta Mol Cell Biol 23 2003 4319 4330
85. I. Wu, S.C. Shin, Y. Cao, I.K. Bender, N. Jafari, and G. Feng Selective glucocorticoid receptor translational isoforms reveal glucocorticoid-induced apoptotic transcriptomes Cell Death Dis 4 2013 e453
86. K.L. Gross, R.H. Oakley, A.B. Scoltock, C.M. Jewell, and J.A. Cidlowski Glucocorticoid receptor α isoform-selective regulation of antiapoptotic genes in osteosarcoma cells: a new mechanism for glucocorticoid resistance Mol Endocrinol 25 2011 1087 1099
87. I.K. Bender, Y. Cao, and N.Z. Lu Determinants of the heightened activity of glucocorticoid receptor translational isoforms Mol Endocrinol 27 2013 1577 1587
88. A. Nehme, E.K. Lobenhofer, W.D. Stamer, and J.L. Edelman Glucocorticoids with different chemical structures but similar glucocorticoid receptor potency regulate subsets of common and unique genes in human trabecular meshwork cells BMC Med Genomics 2 2009 58
89. Y. Cao, I.K. Bender, A.K. Konstantinidis, S.C. Shin, C.M. Jewell, and J.A. Cidlowski Glucocorticoid receptor translational isoforms underlie maturational stage-specific glucocorticoid sensitivities of dendritic cells in mice and humans Blood 121 2013 1553 1562
90. S.C. Wang, S. Myers, C. Dooms, R. Capon, and G.E. Muscat An ERRbeta/gamma agonist modulates GRalpha expression, and glucocorticoid responsive gene expression in skeletal muscle cells Mol Cell Endocrinol 315 2010 146 152
91. D. Sinclair, M.J. Webster, J. Wong, and C.S. Weickert Dynamic molecular and anatomical changes in the glucocorticoid receptor in human cortical development Mol Psychiatry 16 2011 504 515
92. D. Sinclair, M.J. Webster, J.M. Fullerton, and C.S. Weickert Glucocorticoid receptor mRNA and protein isoform alterations in the orbitofrontal cortex in schizophrenia and bipolar disorder BMC Psychiatry 12 2012 84
93. D. Sinclair, S.Y. Tsai, H.G. Woon, and C.S. Weickert Abnormal glucocorticoid receptor mRNA and protein isoform expression in the prefrontal cortex in psychiatric illness Neuropsychopharmacology 36 2011 2698 2709
94. K.B. Pedersen, C.D. Geng, and W.V. Vedeckis Three mechanisms are involved in glucocorticoid receptor autoregulation in a human T-lymphoblast cell line Biochemistry 43 2004 10851 10858
95. H. Russcher, E.F. van Rossum, F.H. de Jong, A.O. Brinkmann, S.W. Lamberts, and J.W. Koper Increased expression of the glucocorticoid receptor-A translational isoform as a result of the ER22/23EK polymorphism Mol Endocrinol 19 2005 1687 1696
96. I.M. Beck, W. Vanden Berghe, L. Vermeulen, K.R. Yamamoto, G. Haegeman, and K. De Bosscher Crosstalk in inflammation: the interplay of glucocorticoid receptor-based mechanisms and kinases and phosphatases Endocr Rev 30 2009 830 882
97. A.J. Galliher-Beckley, and J.A. Cidlowski Emerging roles of glucocorticoid receptor phosphorylation in modulating glucocorticoid hormone action in health and disease IUBMB Life 61 2009 979 986
98. R. Kumar, and W.J. Calhoun Differential regulation of the transcriptional activity of the glucocorticoid receptor through site-specific phosphorylation Biologics 2 2008 845 854
99. Z. Wang, J. Frederick, and M.J. Garabedian Deciphering the phosphorylation "code" of the glucocorticoid receptor in vivo J Biol Chem 277 2002 26573 26580
100. C. Avenant, K. Ronacher, E. Stubsrud, A. Louw, and J.P. Hapgood Role of ligand-dependent GR phosphorylation and half-life in determination of ligand-specific transcriptional activity Mol Cell Endocrinol 327 2010 72 88
101. A.J. Galliher-Beckley, J.G. Williams, and J.A. Cidlowski Ligand-independent phosphorylation of the glucocorticoid receptor integrates cellular stress pathways with nuclear receptor signaling Mol Cell Biol 31 2011 4663 4675
102. J.C. Webster, C.M. Jewell, J.E. Bodwell, A. Munck, M. Sar, and J.A. Cidlowski Mouse glucocorticoid receptor phosphorylation status influences multiple functions of the receptor protein J Biol Chem 272 1997 9287 9293
103. R.D. Blind, and M.J. Garabedian Differential recruitment of glucocorticoid receptor phospho-isoforms to glucocorticoid-induced genes J Steroid Biochem Mol Biol 109 2008 150 157
104. W. Chen, T. Dang, R.D. Blind, Z. Wang, C.N. Cavasotto, and A.B. Hittelman Glucocorticoid receptor phosphorylation differentially affects target gene expression Mol Endocrinol 22 2008 1754 1766
105. A.L. Miller, A.S. Garza, B.H. Johnson, and E.B. Thompson Pathway interactions between MAPKs, mTOR, PKA, and the glucocorticoid receptor in lymphoid cells Cancer Cell Int 7 2007 3
106. A.L. Miller, M.S. Webb, A.J. Copik, Y. Wang, B.H. Johnson, and R. Kumar p38 Mitogen-activated protein kinase (MAPK) is a key mediator in glucocorticoid-induced apoptosis of lymphoid cells: correlation between p38 MAPK activation and site-specific phosphorylation of the human glucocorticoid receptor at serine 211 Mol Endocrinol 19 2005 1569 1583
107. I. Simic, N.P. Maric, M. Mitic, I. Soldatovic, Z. Pavlovic, and M. Mihaljevic Phosphorylation of leukocyte glucocorticoid receptor in patients with current episode of major depressive disorder Prog Neuropsychopharmacol Biol Psychiatry 40 2013 281 285
108. A.J. Galliher-Beckley, J.G. Williams, J.B. Collins, and J.A. Cidlowski Glycogen synthase kinase 3beta-mediated serine phosphorylation of the human glucocorticoid receptor redirects gene expression profiles Mol Cell Biol 28 2008 7309 7322
109. N. Ismaili, R. Blind, and M.J. Garabedian Stabilization of the unliganded glucocorticoid receptor by TSG101 J Biol Chem 280 2005 11120 11126
110. 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 16 2002 2382 2392
111. B.J. Deroo, C. Rentsch, S. Sampath, J. Young, D.B. DeFranco, and T.K. Archer Proteasomal inhibition enhances glucocorticoid receptor transactivation and alters its subnuclear trafficking Mol Cell Biol 22 2002 4113 4123
112. A.D. Wallace, and J.A. Cidlowski Proteasome-mediated glucocorticoid receptor degradation restricts transcriptional signaling by glucocorticoids J Biol Chem 276 2001 42714 42721
113. X. Wang, and D.B. DeFranco Alternative effects of the ubiquitin-proteasome pathway on glucocorticoid receptor down-regulation and transactivation are mediated by CHIP, an E3 ligase Mol Endocrinol 19 2005 1474 1482
114. J. Druker, A.C. Liberman, M. Antunica-Noguerol, J. Gerez, M. Paez-Pereda, and T. Rein RSUME enhances glucocorticoid receptor SUMOylation and transcriptional activity Mol Cell Biol 33 2013 2116 2127
115. L. Davies, N. Karthikeyan, J.T. Lynch, E.A. Sial, A. Gkourtsa, and C. Demonacos Cross talk of signaling pathways in the regulation of the glucocorticoid receptor function Mol Endocrinol 22 2008 1331 1344
116. S. Holmstrom, M.E. Van Antwerp, and J.A. Iniguez-Lluhi Direct and distinguishable inhibitory roles for SUMO isoforms in the control of transcriptional synergy Proc Natl Acad Sci U S A 100 2003 15758 15763
117. S.R. Holmstrom, S. Chupreta, A.Y. So, and J.A. Iniguez-Lluhi Sumo-mediated inhibition of glucocorticoid receptor synergistic activity depends on stable assembly at the promoter but not on DAXX Mol Endocrinol 22 2008 2061 2075
118. Y. Le Drean, N. Mincheneau, P. Le Goff, and D. Michel Potentiation of glucocorticoid receptor transcriptional activity by sumoylation Endocrinology 143 2002 3482 3489
119. S. Tian, H. Poukka, J.J. Palvimo, and O.A. Janne Small ubiquitin-related modifier-1 (SUMO-1) modification of the glucocorticoid receptor Biochem J 367 2002 907 911
120. K. Ito, S. Yamamura, S. Essilfie-Quaye, B. Cosio, M. Ito, and P.J. Barnes Histone deacetylase 2-mediated deacetylation of the glucocorticoid receptor enables NF-kappaB suppression J Exp Med 203 2006 7 13
121. E. Charmandari, G.P. Chrousos, G.I. Lambrou, A. Pavlaki, H. Koide, and S.S. Ng Peripheral CLOCK regulates target-tissue glucocorticoid receptor transcriptional activity in a circadian fashion in man PLoS One 6 2011 e25612
122. B.J. Fan, D.Y. Wang, C.C. Tham, D.S. Lam, and C.P. Pang Gene expression profiles of human trabecular meshwork cells induced by triamcinolone and dexamethasone Invest Ophthalmol Vis Sci 49 2008 1886 1897
123. I.M. Adcock, Y. Nasuhara, D.A. Stevens, and P.J. Barnes Ligand-induced differentiation of glucocorticoid receptor (GR) trans-repression and transactivation: preferential targetting of NF-kappaB and lack of I-kappaB involvement Br J Pharmacol 127 1999 1003 1011
124. S.H. Chen, K. Masuno, S.B. Cooper, and K.R. Yamamoto Incoherent feed-forward regulatory logic underpinning glucocorticoid receptor action Proc Natl Acad Sci U S A 110 2013 1964 1969
125. P.J. Barnes Corticosteroid resistance in patients with asthma and chronic obstructive pulmonary disease J Allergy Clin Immunol 131 2013 636 645
126. N. Yang, D.W. Ray, and L.C. Matthews Current concepts in glucocorticoid resistance Steroids 77 2012 1041 1049
127. A.R. Clark, and M.G. Belvisi Maps and legends: the quest for dissociated ligands of the glucocorticoid receptor Pharmacol Ther 134 2012 54 67
128. S. Vandevyver, L. Dejager, J. Tuckermann, and C. Libert New insights into the anti-inflammatory mechanisms of glucocorticoids: an emerging role for glucocorticoid-receptor-mediated transactivation Endocrinology 154 2013 993 1007