View source for Glucocorticoid receptor

{{Infobox_gene}}
The '''glucocorticoid receptor''' ('''GR''', or '''GCR''') also known as '''NR3C1''' ([[nuclear receptor]] subfamily 3, group C, member 1) is the [[Receptor (biochemistry)|receptor]] to which [[cortisol]] and other [[glucocorticoid]]s bind.

The GR is [[Gene expression|expressed]] in almost every cell in the body and regulates [[gene]]s controlling the [[developmental biology|development]], [[metabolism]], and [[Immune system|immune response]].  Because the receptor gene is expressed in several forms, it has many different ([[pleiotropic]]) effects in different parts of the body.

When the GR binds to glucocorticoids, its primary mechanism of action is the regulation of gene transcription.<ref name="Lu">{{cite journal |vauthors=Lu NZ, Wardell SE, Burnstein KL, Defranco D, Fuller PJ, Giguere V, Hochberg RB, McKay L, Renoir JM, Weigel NL, Wilson EM, McDonnell DP, Cidlowski JA |title=International Union of Pharmacology. LXV. The pharmacology and classification of the nuclear receptor superfamily: glucocorticoid, mineralocorticoid, progesterone, and androgen receptors |journal=Pharmacol Rev |volume=58 |issue=4 |pages=782–97 |year=2006 |pmid= 17132855 | doi = 10.1124/pr.58.4.9}} [Free full text]</ref><ref name="pmid16236742">{{cite journal |vauthors=Rhen T, Cidlowski JA | title = Antiinflammatory action of glucocorticoids--new mechanisms for old drugs | journal = N. Engl. J. Med. | volume = 353 | issue = 16 | pages = 1711–23 |date=October 2005 | pmid = 16236742 | doi = 10.1056/NEJMra050541 | url = | issn = }}</ref> The unbound receptor resides in the [[cytosol]] of the cell. After the receptor is bound to glucocorticoid, the receptor-glucocorticoid complex can take either of two paths. The activated GR complex up-regulates the expression of anti-inflammatory proteins in the nucleus or represses the expression of pro-inflammatory proteins in the cytosol (by preventing the translocation of other [[transcription factor]]s from the cytosol into the nucleus).

In humans, the GR protein is encoded by ''NR3C1''  [[gene]] which is located on [[chromosome 5 (human)|chromosome 5]] (5q31).<ref name="pmid2867473">{{cite journal |vauthors=Hollenberg SM, Weinberger C, Ong ES, Cerelli G, Oro A, Lebo R, Thompson EB, Rosenfeld MG, Evans RM | title = Primary structure and expression of a functional human glucocorticoid receptor cDNA | journal = Nature | volume = 318 | issue = 6047 | pages = 635–41 | year = 1985 | pmid = 2867473 | doi = 10.1038/318635a0| url = | issn = | bibcode = 1985Natur.318..635H}}</ref><ref name="pmid2744768">{{cite journal |vauthors=Francke U, Foellmer BE | title = The glucocorticoid receptor gene is in 5q31-q32 [corrected] | journal = Genomics | volume = 4 | issue = 4 | pages = 610–2 |date=May 1989 | pmid = 2744768 | doi = 10.1016/0888-7543(89)90287-5| url = | issn = }}</ref>

== Structure ==

Like the other [[steroid receptors]],<ref name="pmid10406480">{{cite journal |vauthors=Kumar R, Thompson EB | title = The structure of the nuclear hormone receptors | journal = Steroids | volume = 64 | issue = 5 | pages = 310–9 | year = 1999 | pmid = 10406480 | doi = 10.1016/S0039-128X(99)00014-8 | issn = }}</ref> the glucocorticoid receptor is modular in structure<ref name="pmid15876404">{{cite journal |vauthors=Kumar R, Thompson EB | title = Gene regulation by the glucocorticoid receptor: structure:function relationship | journal = J. Steroid Biochem. Mol. Biol. | volume = 94 | issue = 5 | pages = 383–94 | year = 2005 | pmid = 15876404 | doi = 10.1016/j.jsbmb.2004.12.046 | issn = }}</ref> and contains the following domains (labeled '''A''' - '''F'''):
* '''A/B''' - [[N-terminus|N-terminal]] regulatory domain
* '''C''' - [[DNA-binding domain]] (DBD)
* '''D''' - hinge region
* '''E''' - ligand-binding domain (LBD)
* '''F''' - [[C-terminus|C-terminal]] domain

== Ligand binding and response ==

In the absence of hormone, the glucocorticoid receptor (GR) resides in the cytosol complexed with a variety of proteins including [[heat shock protein]] 90 ([[hsp90]]), the heat shock protein 70 ([[hsp70]]) and the protein [[FKBP52]] ([[FK506]]-binding protein 52).<ref name="Pratt">{{cite journal |vauthors=Pratt WB, Morishima Y, Murphy M, Harrell M |title=Chaperoning of glucocorticoid receptors |journal=Handb Exp Pharmacol |volume=172 |issue= 172|pages=111–38 |year=2006 |pmid= 16610357 |doi=10.1007/3-540-29717-0_5}}</ref>  The endogenous glucocorticoid hormone [[cortisol]] diffuses through the [[cell membrane]] into the [[cytoplasm]] and binds to the  glucocorticoid receptor (GR) resulting in release of the heat shock proteins.  The resulting activated form GR has two principal mechanisms of action, transactivation and transrepression,<ref name="Buckingham">{{cite journal |author=Buckingham JC |title=Glucocorticoids: exemplars of multi-tasking |journal= Br J Pharmacol |volume= 147 |issue=Supplement 1 |pages=S258–68 |year=2006 |pmid= 16402112 | doi = 10.1038/sj.bjp.0706456 |pmc=1760726}}</ref><ref name="Hayashi">{{cite journal |vauthors=Hayashi R, Wada H, Ito K, Adcock IM |title=Effects of glucocorticoids on gene transcription |journal= Eur J Pharmacol |volume= 500 |issue=1-3 |pages=51–62 |year= 2004 |pmid= 15464020 | doi = 10.1016/j.ejphar.2004.07.011}}</ref> described below.

=== Transactivation ===

A direct mechanism of action involves [[homodimerization]] of the receptor, translocation via active transport into the [[Cell nucleus|nucleus]], and binding to specific [[DNA responsive element]]s activating gene [[Transcription (genetics)|transcription]]. This mechanism of action is referred to as [[transactivation]].  The biological response depends on the cell type.

=== Transrepression ===

In the absence of activated GR, other transcription factors such as [[NF-κB]] or [[AP-1 (transcription factor)|AP-1]] themselves are able to transactivate target genes.<ref name="pmid8290595">{{cite journal |vauthors=Ray A, Prefontaine KE | title = Physical association and functional antagonism between the p65 subunit of transcription factor NF-kappa B and the glucocorticoid receptor | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 91 | issue = 2 | pages = 752–6 |date=January 1994 | pmid = 8290595 | pmc = 43027 | doi = 10.1073/pnas.91.2.752| bibcode = 1994PNAS...91..752R }}</ref>  However activated GR can complex with these other transcription factors and prevent them from binding their target genes and hence repress the expression of genes that are normally upregulated by NF-κB or AP-1. This indirect mechanism of action is referred to as [[transrepression]].

== Clinical significance ==

The GR is abnormal in [[familial glucocorticoid resistance]].<ref>{{cite journal |vauthors=Mendonca B, Leite M, de Castro M, Kino T, Elias L, Bachega T, Arnhold I, Chrousos G, Latronico A |title=Female pseudohermaphroditism caused by a novel homozygous missense mutation of the GR gene |journal=J Clin Endocrinol Metab |volume=87 |issue=4 |pages=1805–9 | doi = 10.1210/jc.87.4.1805 |year=2002 |pmid=11932321}}</ref>

In [[central nervous system]] structures, the glucocorticoid receptor is gaining interest as a novel representative of [[neuroendocrine]] integration, functioning as a major component of endocrine influence - specifically the stress response - upon the brain. The receptor is now implicated in both short and long-term adaptations seen in response to stressors and may be critical to the understanding of psychological disorders, including some or all subtypes of [[Depression (mood)|depression]] and [[post-traumatic stress disorder]] ([[PTSD]]).<ref name="Maletic">{{cite journal |vauthors=Maletic V, Robinson M, Oakes T, Iyengar S, Ball SG, Russell J |title=Neurobiology of depression: an integrated view of key findings |journal=Int J Clin Pract |volume=61 |issue=12 |pages=2030–40 |year=2007 |pmid= 17944926 |pmc=2228409 | doi = 10.1111/j.1742-1241.2007.01602.x}} [Free full text]</ref> Indeed, long-standing observations such as the mood dysregulations typical of [[Cushing's disease]] demonstrate the role of corticosteroids in regulating psychologic state; recent advances have demonstrated interactions with [[norepinephrine]] and [[serotonin]] at the neural level.<ref name="Savitz">{{cite journal |vauthors=Savitz J, Lucki I, Drevets WC |title= 5HT1A receptor function in Major Depressive Disorder |journal=Prog Neurobiol |volume=88 |issue=1 |pages=17–31 |year=2009 |pmid= 19428959 |pmc= 2736801 | doi = 10.1016/j.pneurobio.2009.01.009}} [Free full text]</ref><ref>Schechter DS, Moser DA, Paoloni-Giacobino A, Stenz A, Gex-Fabry M, Aue T, Adouan W, Cordero MI, Suardi F, Manini A, Sancho Rossignol A, Merminod G, Ansermet F, Dayer AG, Rusconi Serpa S (epub May 29, 2015). Methylation of NR3C1 is related to maternal PTSD, parenting stress and maternal medial prefrontal cortical activity in response to child separation among mothers with histories of violence exposure. Frontiers in Psychology. To view the online publication, please click here: http://www.frontiersin.org/Journal/Abstract.aspx?s=944&name=psychology_for_clinical_settings&ART_DOI=10.3389/fpsyg.2015.00690&field=&journalName=Frontiers_in_Psychology&id=139466{{dead link|date=October 2017 |bot=InternetArchiveBot |fix-attempted=yes }}</ref>

==Agonists and antagonists==
[[Dexamethasone]] and other [[corticosteroid]]s are [[agonist]]s, and [[mifepristone]] and [[ketoconazole]] are [[receptor antagonist|antagonist]]s of the GR.

==Interactions==
Glucocorticoid receptor has been shown to [[Protein-protein interaction|interact]] with:
{{div col|colwidth=20em}}
* [[BAG1]],<ref name="pmid9603979">{{cite journal |vauthors=Kullmann M, Schneikert J, Moll J, Heck S, Zeiner M, Gehring U, Cato AC | title = RAP46 is a negative regulator of glucocorticoid receptor action and hormone-induced apoptosis | journal = J. Biol. Chem. | volume = 273 | issue = 23 | pages = 14620–5 |date=June 1998 | pmid = 9603979 | doi = 10.1074/jbc.273.23.14620 | url = | issn = }}</ref><ref name="pmid11101523">{{cite journal |vauthors=Schneikert J, Hübner S, Langer G, Petri T, Jäättelä M, Reed J, Cato AC | title = Hsp70-RAP46 interaction in downregulation of DNA binding by glucocorticoid receptor | journal = EMBO J. | volume = 19 | issue = 23 | pages = 6508–16 |date=December 2000 | pmid = 11101523 | pmc = 305849 | doi = 10.1093/emboj/19.23.6508 | url = | issn = }}</ref>
* [[CEBPB]],<ref name="pmid9817600">{{cite journal |vauthors=Boruk M, Savory JG, Haché RJ | title = AF-2-dependent potentiation of CCAAT enhancer binding protein beta-mediated transcriptional activation by glucocorticoid receptor | journal = Mol. Endocrinol. | volume = 12 | issue = 11 | pages = 1749–63 |date=November 1998 | pmid = 9817600 | doi = 10.1210/mend.12.11.0191 | url = | issn = }}</ref>
* [[CREB-binding protein|CREBBP]],<ref name="pmid9649342">{{cite journal |vauthors=Almlöf T, Wallberg AE, Gustafsson JA, Wright AP | title = Role of important hydrophobic amino acids in the interaction between the glucocorticoid receptor tau 1-core activation domain and target factors | journal = Biochemistry | volume = 37 | issue = 26 | pages = 9586–94 |date=June 1998 | pmid = 9649342 | doi = 10.1021/bi973029x | url = | issn = }}</ref>
* [[DAP3]],<ref name="pmid10903152">{{cite journal |vauthors=Hulkko SM, Wakui H, Zilliacus J | title = The pro-apoptotic protein death-associated protein 3 (DAP3) interacts with the glucocorticoid receptor and affects the receptor function | journal = Biochem. J. | volume = Pt 3 | issue = | pages = 885–93 |date=August 2000 | series = 349  | pmid = 10903152 | pmc = 1221218 | doi = 10.1042/bj3490885| url = | issn = }}</ref>
* [[Death associated protein 6|DAXX]],<ref name="pmid12595526">{{cite journal |vauthors=Lin DY, Lai MZ, Ann DK, Shih HM | title = Promyelocytic leukemia protein (PML) functions as a glucocorticoid receptor co-activator by sequestering Daxx to the PML oncogenic domains (PODs) to enhance its transactivation potential | journal = J. Biol. Chem. | volume = 278 | issue = 18 | pages = 15958–65 |date=May 2003 | pmid = 12595526 | doi = 10.1074/jbc.M300387200 | url = | issn = }}</ref>
* [[Heat shock protein 90kDa alpha (cytosolic), member A1|HSP90AA1]],<ref name=pmid10903152/><ref name="pmid10066374">{{cite journal |vauthors=Jibard N, Meng X, Leclerc P, Rajkowski K, Fortin D, Schweizer-Groyer G, Catelli MG, Baulieu EE, Cadepond F | title = Delimitation of two regions in the 90-kDa heat shock protein (Hsp90) able to interact with the glucocorticosteroid receptor (GR) | journal = Exp. Cell Res. | volume = 247 | issue = 2 | pages = 461–74 |date=March 1999 | pmid = 10066374 | doi = 10.1006/excr.1998.4375 | url = | issn = }}</ref><ref name="pmid12093808">{{cite journal |vauthors=Kanelakis KC, Shewach DS, Pratt WB | title = Nucleotide binding states of hsp70 and hsp90 during sequential steps in the process of glucocorticoid receptor.hsp90 heterocomplex assembly | journal = J. Biol. Chem. | volume = 277 | issue = 37 | pages = 33698–703 |date=September 2002 | pmid = 12093808 | doi = 10.1074/jbc.M204164200 | url = | issn = }}</ref><ref name="pmid9334248">{{cite journal |vauthors=Hecht K, Carlstedt-Duke J, Stierna P, Gustafsson J, Brönnegârd M, Wikström AC | title = Evidence that the beta-isoform of the human glucocorticoid receptor does not act as a physiologically significant repressor | journal = J. Biol. Chem. | volume = 272 | issue = 42 | pages = 26659–64 |date=October 1997 | pmid = 9334248 | doi = 10.1074/jbc.272.42.26659 | url = | issn = }}</ref><ref name="pmid8898375">{{cite journal |vauthors=de Castro M, Elliot S, Kino T, Bamberger C, Karl M, Webster E, Chrousos GP | title = The non-ligand binding beta-isoform of the human glucocorticoid receptor (hGR beta): tissue levels, mechanism of action, and potential physiologic role | journal = Mol. Med. | volume = 2 | issue = 5 | pages = 597–607 |date=September 1996 | pmid = 8898375 | pmc = 2230188 | doi = | url = | issn = }}</ref><ref name="pmid8645634">{{cite journal |vauthors=van den Berg JD, Smets LA, van Rooij H | title = Agonist-free transformation of the glucocorticoid receptor in human B-lymphoma cells | journal = J. Steroid Biochem. Mol. Biol. | volume = 57 | issue = 3-4 | pages = 239–49 |date=February 1996 | pmid = 8645634 | doi = 10.1016/0960-0760(95)00271-5 | url = | issn = }}</ref><ref name="pmid8621522">{{cite journal |vauthors=Stancato LF, Silverstein AM, Gitler C, Groner B, Pratt WB | title = Use of the thiol-specific derivatizing agent N-iodoacetyl-3-[125I]iodotyrosine to demonstrate conformational differences between the unbound and hsp90-bound glucocorticoid receptor hormone binding domain | journal = J. Biol. Chem. | volume = 271 | issue = 15 | pages = 8831–6 |date=April 1996 | pmid = 8621522 | doi = 10.1074/jbc.271.15.8831 | url = | issn = }}</ref>
* [[HNRPU]],<ref name="pmid9353307">{{cite journal |vauthors=Eggert M, Michel J, Schneider S, Bornfleth H, Baniahmad A, Fackelmayer FO, Schmidt S, Renkawitz R | title = The glucocorticoid receptor is associated with the RNA-binding nuclear matrix protein hnRNP U | journal = J. Biol. Chem. | volume = 272 | issue = 45 | pages = 28471–8 |date=November 1997 | pmid = 9353307 | doi = 10.1074/jbc.272.45.28471 | url = | issn = }}</ref>
* [[MED1]],<ref name=pmid11266503/><ref name=pmid10508170/>
* [[MED14]],<ref name="pmid10508170">{{cite journal |vauthors=Hittelman AB, Burakov D, Iñiguez-Lluhí JA, Freedman LP, Garabedian MJ | title = Differential regulation of glucocorticoid receptor transcriptional activation via AF-1-associated proteins | journal = EMBO J. | volume = 18 | issue = 19 | pages = 5380–8 |date=October 1999 | pmid = 10508170 | pmc = 1171607 | doi = 10.1093/emboj/18.19.5380 | url = | issn = }}</ref>
* [[Mineralocorticoid receptor]],<ref name="pmid11154266">{{cite journal |vauthors=Savory JG, Préfontaine GG, Lamprecht C, Liao M, Walther RF, Lefebvre YA, Haché RJ | title = Glucocorticoid receptor homodimers and glucocorticoid-mineralocorticoid receptor heterodimers form in the cytoplasm through alternative dimerization interfaces | journal = Mol. Cell. Biol. | volume = 21 | issue = 3 | pages = 781–93 |date=February 2001 | pmid = 11154266 | pmc = 86670 | doi = 10.1128/MCB.21.3.781-793.2001 | url = | issn = }}</ref>
* [[NRIP1]],<ref name=pmid11266503/><ref name="pmid12773562">{{cite journal |vauthors=Tazawa H, Osman W, Shoji Y, Treuter E, Gustafsson JA, Zilliacus J | title = Regulation of subnuclear localization is associated with a mechanism for nuclear receptor corepression by RIP140 | journal = Mol. Cell. Biol. | volume = 23 | issue = 12 | pages = 4187–98 |date=June 2003 | pmid = 12773562 | pmc = 156128 | doi = 10.1128/MCB.23.12.4187-4198.2003 | url = | issn = }}</ref><ref name="pmid10364267">{{cite journal |vauthors=Subramaniam N, Treuter E, Okret S | title = Receptor interacting protein RIP140 inhibits both positive and negative gene regulation by glucocorticoids | journal = J. Biol. Chem. | volume = 274 | issue = 25 | pages = 18121–7 |date=June 1999 | pmid = 10364267 | doi = 10.1074/jbc.274.25.18121 | url = | issn = }}</ref>
* [[Nuclear receptor co-repressor 1|NCOR1]],<ref name="pmid12569182">{{cite journal |vauthors=Stevens A, Garside H, Berry A, Waters C, White A, Ray D | title = Dissociation of steroid receptor coactivator 1 and nuclear receptor corepressor recruitment to the human glucocorticoid receptor by modification of the ligand-receptor interface: the role of tyrosine 735 | journal = Mol. Endocrinol. | volume = 17 | issue = 5 | pages = 845–59 |date=May 2003 | pmid = 12569182 | doi = 10.1210/me.2002-0320 | url = | issn = }}</ref><ref name="pmid12011091">{{cite journal |vauthors=Schulz M, Eggert M, Baniahmad A, Dostert A, Heinzel T, Renkawitz R | title = RU486-induced glucocorticoid receptor agonism is controlled by the receptor N terminus and by corepressor binding | journal = J. Biol. Chem. | volume = 277 | issue = 29 | pages = 26238–43 |date=July 2002 | pmid = 12011091 | doi = 10.1074/jbc.M203268200 | url = | issn = }}</ref>
* [[Nuclear receptor coactivator 1|NCOA1]],<ref name=pmid11266503/><ref name="pmid12118039">{{cite journal |vauthors=Kucera T, Waltner-Law M, Scott DK, Prasad R, Granner DK | title = A point mutation of the AF2 transactivation domain of the glucocorticoid receptor disrupts its interaction with steroid receptor coactivator 1 | journal = J. Biol. Chem. | volume = 277 | issue = 29 | pages = 26098–102 |date=July 2002 | pmid = 12118039 | doi = 10.1074/jbc.M204013200 | url = | issn = }}</ref>
* [[Nuclear receptor coactivator 2|NCOA2]],<ref name="pmid11266503">{{cite journal |vauthors=Zilliacus J, Holter E, Wakui H, Tazawa H, Treuter E, Gustafsson  JA | title = Regulation of glucocorticoid receptor activity by 14--3-3-dependent intracellular relocalization of the corepressor RIP140 | journal = Mol. Endocrinol. | volume = 15 | issue = 4 | pages = 501–11 |date=April 2001 | pmid = 11266503 | doi = 10.1210/mend.15.4.0624 | url = | issn = }}</ref><ref name="pmid12151000">{{cite journal |vauthors=Bledsoe RK, Montana VG, Stanley TB, Delves CJ, Apolito CJ, McKee DD, Consler TG, Parks DJ, Stewart EL, Willson TM, Lambert MH, Moore JT, Pearce KH, Xu HE | title = Crystal structure of the glucocorticoid receptor ligand binding domain reveals a novel mode of receptor dimerization and coactivator recognition | journal = Cell | volume = 110 | issue = 1 | pages = 93–105 |date=July 2002 | pmid = 12151000 | doi = 10.1016/S0092-8674(02)00817-6 | url = | issn = }}</ref>
* [[Nuclear receptor coactivator 3|NCOA3]],<ref name=pmid11266503/><ref name="pmid12917342">{{cite journal |vauthors=Hsiao PW, Fryer CJ, Trotter KW, Wang W, Archer TK | title = BAF60a mediates critical interactions between nuclear receptors and the BRG1 chromatin-remodeling complex for transactivation | journal = Mol. Cell. Biol. | volume = 23 | issue = 17 | pages = 6210–20 |date=September 2003 | pmid = 12917342 | pmc = 180928 | doi = 10.1128/MCB.23.17.6210-6220.2003 | url = | issn = }}</ref>
* [[POU2F1]],<ref name=pmid10480874>{{cite journal |doi=10.1074/jbc.274.38.26713 |last=Préfontaine |first=G G |authorlink= |author2=Walther R |author3=Giffin W |author4=Lemieux M E |author5=Pope L |author6=Haché R J  |date=Sep 1999 |title=Selective binding of steroid hormone receptors to octamer transcription factors determines transcriptional synergism at the mouse mammary tumor virus promoter |journal=J. Biol. Chem. |volume=274 |issue=38 |pages=26713–9 |publisher= |location = UNITED STATES| issn = 0021-9258| pmid = 10480874 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = }}</ref><ref name="pmid10480874" /><ref name="pmid9584182">{{cite journal |vauthors=Préfontaine GG, Lemieux ME, Giffin W, Schild-Poulter C, Pope L, LaCasse E, Walker P, Haché RJ | title = Recruitment of octamer transcription factors to DNA by glucocorticoid receptor | journal = Mol. Cell. Biol. | volume = 18 | issue = 6 | pages = 3416–30 |date=June 1998 | pmid = 9584182 | pmc = 108923 | doi = | url = | issn = }}</ref>
* [[RANBP9]],<ref name=pmid12361945>{{cite journal |last=Rao |first=Mira A |authorlink= |author2=Cheng Helen |author3=Quayle Alandra N |author4=Nishitani Hideo |author5=Nelson Colleen C |author6=Rennie Paul S  |date=Dec 2002 |title=RanBPM, a nuclear protein that interacts with and regulates transcriptional activity of androgen receptor and glucocorticoid receptor |journal=J. Biol. Chem. |volume=277 |issue=50 |pages=48020–7 |publisher= |location = United States| issn = 0021-9258| pmid = 12361945 |doi = 10.1074/jbc.M209741200 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = }}</ref>
* [[RELA]],<ref name="pmid12361945" /><ref name="pmid10995388">{{cite journal |vauthors=Nissen RM, Yamamoto KR | title = The glucocorticoid receptor inhibits NFkappaB by interfering with serine-2 phosphorylation of the RNA polymerase II carboxy-terminal domain | journal = Genes Dev. | volume = 14 | issue = 18 | pages = 2314–29 |date=September 2000 | pmid = 10995388 | pmc = 316928 | doi = 10.1101/gad.827900 | url = | issn = }}</ref><ref name="pmid7659084">{{cite journal |vauthors=Caldenhoven E, Liden J, Wissink S, Van de Stolpe A, Raaijmakers J, Koenderman L, Okret S, Gustafsson JA, Van der Saag PT | title = Negative cross-talk between RelA and the glucocorticoid receptor: a possible mechanism for the antiinflammatory action of glucocorticoids | journal = Mol. Endocrinol. | volume = 9 | issue = 4 | pages = 401–12 |date=April 1995 | pmid = 7659084 | doi = 10.1210/me.9.4.401 | url = | issn = }}</ref>
* [[Mothers against decapentaplegic homolog 3|SMAD3]],<ref name="pmid12902338">{{cite journal |vauthors=Li G, Wang S, Gelehrter TD | title = Identification of glucocorticoid receptor domains involved in transrepression of transforming growth factor-beta action | journal = J. Biol. Chem. | volume = 278 | issue = 43 | pages = 41779–88 |date=October 2003 | pmid = 12902338 | doi = 10.1074/jbc.M305350200 | url = | issn = }}</ref><ref name="pmid10518526">{{cite journal |vauthors=Song CZ, Tian X, Gelehrter TD | title = Glucocorticoid receptor inhibits transforming growth factor-beta signaling by directly targeting the transcriptional activation function of Smad3 | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 96 | issue = 21 | pages = 11776–81 |date=October 1999 | pmid = 10518526 | pmc = 18362 | doi = 10.1073/pnas.96.21.11776 | url = | issn = | bibcode = 1999PNAS...9611776S }}</ref>
* [[SMARCD1]],<ref name=pmid12917342/>
* [[SMARCA4]]<ref name=pmid12917342/><ref name="pmid10688647">{{cite journal |vauthors=Wallberg AE, Neely KE, Hassan AH, Gustafsson JA, Workman JL, Wright AP | title = Recruitment of the SWI-SNF chromatin remodeling complex as a mechanism of gene activation by the glucocorticoid receptor tau1 activation domain | journal = Mol. Cell. Biol. | volume = 20 | issue = 6 | pages = 2004–13 |date=March 2000 | pmid = 10688647 | pmc = 110817 | doi = 10.1128/MCB.20.6.2004-2013.2000 | url = | issn = }}</ref>
* [[STAT3]],<ref name="pmid14522952">{{cite journal |vauthors=Lerner L, Henriksen MA, Zhang X, Darnell JE | title = STAT3-dependent enhanceosome assembly and disassembly: synergy with GR for full transcriptional increase of the alpha 2-macroglobulin gene | journal = Genes Dev. | volume = 17 | issue = 20 | pages = 2564–77 |date=October 2003 | pmid = 14522952 | pmc = 218150 | doi = 10.1101/gad.1135003 | url = | issn = }}</ref><ref name="pmid9388192">{{cite journal |vauthors=Zhang Z, Jones S, Hagood JS, Fuentes NL, Fuller GM | title = STAT3 acts as a co-activator of glucocorticoid receptor signaling | journal = J. Biol. Chem. | volume = 272 | issue = 49 | pages = 30607–10 |date=December 1997 | pmid = 9388192 | doi = 10.1074/jbc.272.49.30607 | url = | issn = }}</ref>
* [[STAT5B]],<ref name="pmid8878484">{{cite journal |vauthors=Stöcklin E, Wissler M, Gouilleux F, Groner B | title = Functional interactions between Stat5 and the glucocorticoid receptor | journal = Nature | volume = 383 | issue = 6602 | pages = 726–8 |date=October 1996 | pmid = 8878484 | doi = 10.1038/383726a0 | url = | issn = | bibcode = 1996Natur.383..726S }}</ref>
* [[Thioredoxin]],<ref name="pmid9915858">{{cite journal |vauthors=Makino Y, Yoshikawa N, Okamoto K, Hirota K, Yodoi J, Makino I, Tanaka H | title = Direct association with thioredoxin allows redox regulation of glucocorticoid receptor function | journal = J. Biol. Chem. | volume = 274 | issue = 5 | pages = 3182–8 |date=January 1999 | pmid = 9915858 | doi = 10.1074/jbc.274.5.3182 | url = | issn = }}</ref>
* [[TRIM28]],<ref name="pmid9742105">{{cite journal |vauthors=Chang CJ, Chen YL, Lee SC | title = Coactivator TIF1beta interacts with transcription factor C/EBPbeta and glucocorticoid receptor to induce alpha1-acid glycoprotein gene expression | journal = Mol. Cell. Biol. | volume = 18 | issue = 10 | pages = 5880–7 |date=October 1998 | pmid = 9742105 | pmc = 109174 | doi = 10.1128/mcb.18.10.5880| url = | issn = }}</ref> and
* [[YWHAH]].<ref name="pmid9079630">{{cite journal |vauthors=Wakui H, Wright AP, Gustafsson J, Zilliacus J | title = Interaction of the ligand-activated glucocorticoid receptor with the 14-3-3 eta protein | journal = J. Biol. Chem. | volume = 272 | issue = 13 | pages = 8153–6 |date=March 1997 | pmid = 9079630 | doi = 10.1074/jbc.272.13.8153 | url = | issn = }}</ref>
{{Div col end}}

==See also==
* [[Membrane glucocorticoid receptor]]
* [[Familial/sporadic glucocorticoid resistance]] (Chrousos Syndrome)
* [[Selective glucocorticoid receptor agonist]] (SEGRA)

==References==
{{reflist|2}}

==Further reading==
{{refbegin | 2}}
*{{cite journal  |vauthors=Adcock IM, Ito K |title=Molecular mechanisms of corticosteroid actions. |journal=Monaldi Archives for Chest Disease |volume=55 |issue= 3 |pages= 256–66 |year= 2000 |pmid= 10948677 |doi=  }}
*{{cite journal  | author=Chikanza IC |title=Mechanisms of corticosteroid resistance in rheumatoid arthritis: a putative role for the corticosteroid receptor beta isoform. |journal=Ann. N. Y. Acad. Sci. |volume=966 |issue=  |pages= 39–48 |year= 2002 |pmid= 12114257 |doi= 10.1111/j.1749-6632.2002.tb04200.x |bibcode=2002NYASA.966...39C }}
*{{cite journal  |vauthors=Neeck G, Kluter A, Dotzlaw H, Eggert M |title=Involvement of the glucocorticoid receptor in the pathogenesis of rheumatoid arthritis. |journal=Ann. N. Y. Acad. Sci. |volume=966 |issue=  1|pages= 491–5 |year= 2002 |pmid= 12114309 |doi=10.1111/j.1749-6632.2002.tb04252.x  |bibcode=2002NYASA.966..491N }}
*{{cite journal  |vauthors=Yudt MR, Cidlowski JA |title=The glucocorticoid receptor: coding a diversity of proteins and responses through a single gene. |journal=Mol. Endocrinol. |volume=16 |issue= 8 |pages= 1719–26 |year= 2003 |pmid= 12145329 |doi=10.1210/me.2002-0106  }}
*{{cite journal  |vauthors=Torrego A, Pujols L, Picado C |title=[Response to glucocorticoid treatment in asthma. The role of alpha and beta isoforms of the glucocorticoid receptor] |journal=Arch. Bronconeumol. |volume=38 |issue= 9 |pages= 436–40 |year= 2003 |pmid= 12237016 |doi=  }}
*{{cite journal  |vauthors=Bray PJ, Cotton RG |title=Variations of the human glucocorticoid receptor gene (NR3C1): pathological and in vitro mutations and polymorphisms. |journal=Hum. Mutat. |volume=21 |issue= 6 |pages= 557–68 |year= 2003 |pmid= 12754700 |doi= 10.1002/humu.10213 }}
*{{cite journal  |vauthors=Kino T, Pavlakis GN |title=Partner molecules of accessory protein Vpr of the human immunodeficiency virus type 1. |journal=DNA Cell Biol. |volume=23 |issue= 4 |pages= 193–205 |year= 2004 |pmid= 15142377 |doi= 10.1089/104454904773819789 }}
*{{cite journal  |vauthors=Lu NZ, Cidlowski JA |title=The origin and functions of multiple human glucocorticoid receptor isoforms. |journal=Ann. N. Y. Acad. Sci. |volume=1024 |issue=  1|pages= 102–23 |year= 2004 |pmid= 15265776 |doi= 10.1196/annals.1321.008 |bibcode=2004NYASA1024..102L }}
*{{cite journal  |vauthors=Kino T, Chrousos GP |title=Human immunodeficiency virus type-1 accessory protein Vpr: a causative agent of the AIDS-related insulin resistance/lipodystrophy syndrome? |journal=Ann. N. Y. Acad. Sci. |volume=1024 |issue=  1|pages= 153–67 |year= 2004 |pmid= 15265780 |doi= 10.1196/annals.1321.013 |bibcode=2004NYASA1024..153K }}
*{{cite journal  |vauthors=Andersen JL, Planelles V |title=The role of Vpr in HIV-1 pathogenesis. |journal=Curr. HIV Res. |volume=3 |issue= 1 |pages= 43–51 |year= 2005 |pmid= 15638722 |doi=10.2174/1570162052772988  }}
*{{cite journal  |vauthors=Le Rouzic E, Benichou S |title=The Vpr protein from HIV-1: distinct roles along the viral life cycle. |journal=Retrovirology |volume=2 |issue=  1|pages= 11 |year= 2006 |pmid= 15725353 |doi= 10.1186/1742-4690-2-11  | pmc=554975 }}
*{{cite journal   |vauthors=Muthumani K, Choo AY, Premkumar A, etal |title=Human immunodeficiency virus type 1 (HIV-1) Vpr-regulated cell death: insights into mechanism.  |journal=Cell Death Differ. |volume= 12 |issue=Suppl 1  |pages= 962–70 |year= 2006 |pmid= 15832179 |doi= 10.1038/sj.cdd.4401583 }}
*{{cite journal  |vauthors=Zhou J, Cidlowski JA |title=The human glucocorticoid receptor: one gene, multiple proteins and diverse responses. |journal=Steroids |volume=70 |issue= 5-7 |pages= 407–17 |year= 2005 |pmid= 15862824 |doi= 10.1016/j.steroids.2005.02.006 }}
*{{cite journal  |vauthors=Chrousos GP, Kino T |title=Intracellular glucocorticoid signaling: a formerly simple system turns stochastic. |journal=Sci. STKE |volume=2005 |issue= 304 |pages= pe48 |year= 2006 |pmid= 16204701 |doi= 10.1126/stke.3042005pe48 }}
*{{cite journal   |vauthors=Plotkin LL, Labutin AL, Lebedev LV, etal |title=[Balloon probe for the removal of emboli and thrombi] |journal=Meditsinskaia tekhnika |volume= |issue= 3 |pages= 42–3 |year= 1975 |pmid= 1152650 |doi=  }}
*{{cite journal   |vauthors=Subramaniam M, Colvard D, Keeting PE, etal |title=Glucocorticoid regulation of alkaline phosphatase, osteocalcin, and proto-oncogenes in normal human osteoblast-like cells. |journal=J. Cell. Biochem. |volume=50 |issue= 4 |pages= 411–24 |year= 1993 |pmid= 1469072 |doi= 10.1002/jcb.240500410 }}
*{{cite journal  |vauthors=Scherrer LC, Pratt WB |title=Association of the transformed glucocorticoid receptor with a cytoskeletal protein complex. |journal=J. Steroid Biochem. Mol. Biol. |volume=41 |issue= 3-8 |pages= 719–21 |year= 1992 |pmid= 1562545 |doi=10.1016/0960-0760(92)90411-B  }}
*{{cite journal   |vauthors=Cadepond F, Gasc JM, Delahaye F, etal |title=Hormonal regulation of the nuclear localization signals of the human glucocorticosteroid receptor. |journal=Exp. Cell Res. |volume=201 |issue= 1 |pages= 99–108 |year= 1992 |pmid= 1612132 |doi=10.1016/0014-4827(92)90352-9  }}
*{{cite journal   |vauthors=Hurley DM, Accili D, Stratakis CA, etal |title=Point mutation causing a single amino acid substitution in the hormone binding domain of the glucocorticoid receptor in familial glucocorticoid resistance. |journal=J. Clin. Invest. |volume=87 |issue= 2 |pages= 680–6 |year= 1991 |pmid= 1704018 |doi=10.1172/JCI115046  | pmc=296359  }}
*{{cite journal  |vauthors=Encío IJ, Detera-Wadleigh SD |title=The genomic structure of the human glucocorticoid receptor. |journal=J. Biol. Chem. |volume=266 |issue= 11 |pages= 7182–8 |year= 1991 |pmid= 1707881 |doi=  }}
{{refend}}

==External links==
* [http://www.hprd.org/protein/00679 Human Protein Reference Database]
* {{MeshName|Glucocorticoid+receptors}}
* {{FactorBook|GR}}

{{PDB Gallery|geneid=2908}}
{{Transcription factors|g2}}
{{Glucocorticoidics}}

[[Category:Intracellular receptors]]
[[Category:Transcription factors]]
[[Category:Genome projects]]