glucocorticoid receptor

{{short description|Receptor to which cortisol and other glucocorticoids bind}}

The glucocorticoid receptor (GR or GCR) also known by its gene name NR3C1 (nuclear receptor subfamily 3, group C, member 1) is the steroid receptor for glucocorticoids such as cortisol.

The GR is expressed in almost every cell in the body and regulates genes controlling the development, metabolism, inflammation, and immune response. Because the receptor gene is expressed in several forms, it has many different (pleiotropic) effects in different parts of the body and in the context of different diseases.

GR is a steroid receptor and thus its canonical action is similar to other steroid receptors.{{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 | display-authors = 6 | title = International Union of Pharmacology. LXV. The pharmacology and classification of the nuclear receptor superfamily: glucocorticoid, mineralocorticoid, progesterone, and androgen receptors | journal = Pharmacological Reviews | volume = 58 | issue = 4 | pages = 782–797 | date = December 2006 | pmid = 17132855 | doi = 10.1124/pr.58.4.9 | s2cid = 28626145 }} [Free full text]{{cite journal | vauthors = Rhen T, Cidlowski JA | title = Antiinflammatory action of glucocorticoids--new mechanisms for old drugs | journal = The New England Journal of Medicine | volume = 353 | issue = 16 | pages = 1711–1723 | date = October 2005 | pmid = 16236742 | doi = 10.1056/NEJMra050541 | s2cid = 5744727 }} The unbound receptor resides in the cytosol of the cell. When glucocorticoids bind to the receptor, GR translocates to the nucleus of the cell where it acts as a transcription factor. 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 factors from the cytosol into the nucleus).

In humans, the GR protein is encoded by {{gene|NR3C1}} gene which is located on chromosome 5 (5q31).{{cite journal | vauthors = Hollenberg SM, Weinberger C, Ong ES, Cerelli G, Oro A, Lebo R, Thompson EB, Rosenfeld MG, Evans RM | display-authors = 6 | title = Primary structure and expression of a functional human glucocorticoid receptor cDNA | journal = Nature | volume = 318 | issue = 6047 | pages = 635–641 | date = December 1985 | pmid = 2867473 | pmc = 6165583 | doi = 10.1038/318635a0 | bibcode = 1985Natur.318..635H }}{{cite journal | vauthors = Francke U, Foellmer BE | title = The glucocorticoid receptor gene is in 5q31-q32 [corrected] | journal = Genomics | volume = 4 | issue = 4 | pages = 610–612 | date = May 1989 | pmid = 2744768 | doi = 10.1016/0888-7543(89)90287-5 }}

Structure

Like the other steroid receptors,{{cite journal | vauthors = Kumar R, Thompson EB | title = The structure of the nuclear hormone receptors | journal = Steroids | volume = 64 | issue = 5 | pages = 310–319 | date = May 1999 | pmid = 10406480 | doi = 10.1016/S0039-128X(99)00014-8 | s2cid = 18333397 }} GR is modular in structure{{cite journal | vauthors = Kumar R, Thompson EB | title = Gene regulation by the glucocorticoid receptor: structure:function relationship | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 94 | issue = 5 | pages = 383–394 | date = April 2005 | pmid = 15876404 | doi = 10.1016/j.jsbmb.2004.12.046 | s2cid = 25315991 }} and contains the following domains (labeled A - F):

A/B - N-terminal regulatory domain
C - DNA-binding domain (DBD)
D - hinge region
E - ligand-binding domain (LBD)
F - 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 FKBP4 (FK506-binding protein 4).{{cite book | vauthors = Pratt WB, Morishima Y, Murphy M, Harrell M | title = Molecular Chaperones in Health and Disease | chapter = Chaperoning of glucocorticoid receptors | volume = 172 | issue = | pages = 111–138 | year = 2006 | pmid = 16610357 | doi = 10.1007/3-540-29717-0_5 | isbn = 978-3-540-25875-9 | series = Handbook of Experimental Pharmacology | publisher = Springer }} The endogenous glucocorticoid hormone cortisol diffuses through the cell membrane into the cytoplasm and binds to the glucocorticoid receptor (GR) resulting in the release of the heat shock proteins. The resulting activated form GR has two principal mechanisms of action, transactivation, and transrepression,{{cite journal | vauthors = Buckingham JC | title = Glucocorticoids: exemplars of multi-tasking | journal = British Journal of Pharmacology | volume = 147 | issue = Supplement 1 | pages = S258–S268 | date = January 2006 | pmid = 16402112 | pmc = 1760726 | doi = 10.1038/sj.bjp.0706456 }}{{cite journal | vauthors = Hayashi R, Wada H, Ito K, Adcock IM | title = Effects of glucocorticoids on gene transcription | journal = European Journal of Pharmacology | volume = 500 | issue = 1–3 | pages = 51–62 | date = October 2004 | pmid = 15464020 | doi = 10.1016/j.ejphar.2004.07.011 }} described below.

= Transactivation =

A direct mechanism of action involves homodimerization of the receptor, translocation via active transport into the nucleus, and binding to specific DNA response elements activating gene transcription. This mechanism of action is referred to as transactivation. The biological response depends on the cell type.{{cn|date=August 2022}}

= Transrepression =

In the absence of activated GR, other transcription factors such as NF-κB or AP-1 themselves are able to transactivate target genes.{{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 = Proceedings of the National Academy of Sciences of the United States of America | volume = 91 | issue = 2 | pages = 752–756 | date = January 1994 | pmid = 8290595 | pmc = 43027 | doi = 10.1073/pnas.91.2.752 | doi-access = free | bibcode = 1994PNAS...91..752R }} 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.{{cn|date=August 2022}} GR transrepression via NF-κB and AP-1 is restricted only to certain cell types, and is not considered the universal mechanism for IκBα repression. {{cite journal | vauthors = Coutinho AE, Chapman KE | title = The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights | journal = Molecular and Cellular Endocrinology | volume = 335 | issue = 1 | pages = 2–13 | date = March 2011 | pmid = 20398732 | pmc = 3047790 | doi = 10.1016/j.mce.2010.04.005 }}{{cite journal | vauthors = Heck S, Bender K, Kullmann M, Göttlicher M, Herrlich P, Cato AC | title = I kappaB alpha-independent downregulation of NF-kappaB activity by glucocorticoid receptor | journal = The EMBO Journal | volume = 16 | issue = 15 | pages = 4698–4707 | date = August 1997 | pmid = 9303314 | pmc = 1170096 | doi = 10.1093/emboj/16.15.4698 }}

Clinical significance

The GR is abnormal in familial glucocorticoid resistance.{{cite journal | vauthors = Mendonca BB, Leite MV, de Castro M, Kino T, Elias LL, Bachega TA, Arnhold IJ, Chrousos GP, Latronico AC | display-authors = 6 | title = Female pseudohermaphroditism caused by a novel homozygous missense mutation of the GR gene | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 87 | issue = 4 | pages = 1805–1809 | date = April 2002 | pmid = 11932321 | doi = 10.1210/jcem.87.4.8379 | doi-access = free }}

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 and post-traumatic stress disorder (PTSD).{{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 = International Journal of Clinical Practice | volume = 61 | issue = 12 | pages = 2030–2040 | date = December 2007 | pmid = 17944926 | pmc = 2228409 | doi = 10.1111/j.1742-1241.2007.01602.x }} [Free full text] 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.{{cite journal | vauthors = Savitz J, Lucki I, Drevets WC | title = 5-HT(1A) receptor function in major depressive disorder | journal = Progress in Neurobiology | volume = 88 | issue = 1 | pages = 17–31 | date = May 2009 | pmid = 19428959 | pmc = 2736801 | doi = 10.1016/j.pneurobio.2009.01.009 }} [Free full text]{{cite journal | vauthors = Schechter DS, Moser DA, Paoloni-Giacobino A, Stenz L, 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 |display-authors = 6| title = 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 | journal = Front Psychol | volume = 6 | issue = | pages = 690 | date = 2015 | pmid = 26074844 | pmc = 4447998 | doi = 10.3389/fpsyg.2015.00690 |doi-access = free}}

In preeclampsia (a hypertensive disorder commonly occurring in pregnant women), the level of a miRNA sequence possibly targeting this protein is elevated in the blood of the mother. Rather, the placenta elevates the level of exosomes containing this miRNA, which can result in inhibition of translation of molecule. Clinical significance of this information is not yet clarified.{{cite journal | vauthors = Salomon C, Guanzon D, Scholz-Romero K, Longo S, Correa P, Illanes SE, Rice GE | title = Placental Exosomes as Early Biomarker of Preeclampsia: Potential Role of Exosomal MicroRNAs Across Gestation | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 102 | issue = 9 | pages = 3182–3194 | date = September 2017 | pmid = 28531338 | doi = 10.1210/jc.2017-00672 | doi-access = free }}

Agonists and antagonists

Dexamethasone and other corticosteroids are agonists, while mifepristone and ketoconazole are antagonists of GR. Anabolic steroids also prevent cortisol from binding to the glucocorticoid receptor.

Interactions

Glucocorticoid receptor has been shown to interact with:

BAG1,{{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 = The Journal of Biological Chemistry | volume = 273 | issue = 23 | pages = 14620–14625 | date = June 1998 | pmid = 9603979 | doi = 10.1074/jbc.273.23.14620 | doi-access = free }}{{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 = The EMBO Journal | volume = 19 | issue = 23 | pages = 6508–6516 | date = December 2000 | pmid = 11101523 | pmc = 305849 | doi = 10.1093/emboj/19.23.6508 }}
CEBPB,{{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 = Molecular Endocrinology | volume = 12 | issue = 11 | pages = 1749–1763 | date = November 1998 | pmid = 9817600 | doi = 10.1210/mend.12.11.0191 | doi-access = }}
CREBBP,{{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 = 9586–9594 | date = June 1998 | pmid = 9649342 | doi = 10.1021/bi973029x }}
DAP3,{{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 = The Biochemical Journal | volume = 349 | issue = 3 | pages = 885–893 | date = August 2000 | pmid = 10903152 | pmc = 1221218 | doi = 10.1042/bj3490885 | series = 349 }}
DAXX,{{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 = The Journal of Biological Chemistry | volume = 278 | issue = 18 | pages = 15958–15965 | date = May 2003 | pmid = 12595526 | doi = 10.1074/jbc.M300387200 | doi-access = free}}
HSP90AA1,{{cite journal | vauthors = Jibard N, Meng X, Leclerc P, Rajkowski K, Fortin D, Schweizer-Groyer G, Catelli MG, Baulieu EE, Cadepond F | display-authors = 6 | title = Delimitation of two regions in the 90-kDa heat shock protein (Hsp90) able to interact with the glucocorticosteroid receptor (GR) | journal = Experimental Cell Research | volume = 247 | issue = 2 | pages = 461–474 | date = March 1999 | pmid = 10066374 | doi = 10.1006/excr.1998.4375 }}{{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 = The Journal of Biological Chemistry | volume = 277 | issue = 37 | pages = 33698–33703 | date = September 2002 | pmid = 12093808 | doi = 10.1074/jbc.M204164200 | doi-access = free }}{{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 = The Journal of Biological Chemistry | volume = 272 | issue = 42 | pages = 26659–26664 | date = October 1997 | pmid = 9334248 | doi = 10.1074/jbc.272.42.26659 | doi-access = free }}{{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 = Molecular Medicine | volume = 2 | issue = 5 | pages = 597–607 | date = September 1996 | pmid = 8898375 | pmc = 2230188 | doi = 10.1007/BF03401643 }}{{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 = The Journal of Steroid Biochemistry and Molecular Biology | volume = 57 | issue = 3–4 | pages = 239–249 | date = February 1996 | pmid = 8645634 | doi = 10.1016/0960-0760(95)00271-5 | s2cid = 20582144 }}{{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 = The Journal of Biological Chemistry | volume = 271 | issue = 15 | pages = 8831–8836 | date = April 1996 | pmid = 8621522 | doi = 10.1074/jbc.271.15.8831 | doi-access = free }}
HNRPU,{{cite journal | vauthors = Eggert M, Michel J, Schneider S, Bornfleth H, Baniahmad A, Fackelmayer FO, Schmidt S, Renkawitz R | display-authors = 6 | title = The glucocorticoid receptor is associated with the RNA-binding nuclear matrix protein hnRNP U | journal = The Journal of Biological Chemistry | volume = 272 | issue = 45 | pages = 28471–28478 | date = November 1997 | pmid = 9353307 | doi = 10.1074/jbc.272.45.28471 | doi-access = free }}
MED1,
MED14,{{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 = The EMBO Journal | volume = 18 | issue = 19 | pages = 5380–5388 | date = October 1999 | pmid = 10508170 | pmc = 1171607 | doi = 10.1093/emboj/18.19.5380 }}
Mineralocorticoid receptor,{{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 = Molecular and Cellular Biology | volume = 21 | issue = 3 | pages = 781–793 | date = February 2001 | pmid = 11154266 | pmc = 86670 | doi = 10.1128/MCB.21.3.781-793.2001 }}
NRIP1,{{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 = Molecular and Cellular Biology | volume = 23 | issue = 12 | pages = 4187–4198 | date = June 2003 | pmid = 12773562 | pmc = 156128 | doi = 10.1128/MCB.23.12.4187-4198.2003 }}{{cite journal | vauthors = Subramaniam N, Treuter E, Okret S | title = Receptor interacting protein RIP140 inhibits both positive and negative gene regulation by glucocorticoids | journal = The Journal of Biological Chemistry | volume = 274 | issue = 25 | pages = 18121–18127 | date = June 1999 | pmid = 10364267 | doi = 10.1074/jbc.274.25.18121 | doi-access = free }}
NCOR1,{{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 = Molecular Endocrinology | volume = 17 | issue = 5 | pages = 845–859 | date = May 2003 | pmid = 12569182 | doi = 10.1210/me.2002-0320 | doi-access = free }}{{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 = The Journal of Biological Chemistry | volume = 277 | issue = 29 | pages = 26238–26243 | date = July 2002 | pmid = 12011091 | doi = 10.1074/jbc.M203268200 | doi-access = free }}
NCOA1,{{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 = The Journal of Biological Chemistry | volume = 277 | issue = 29 | pages = 26098–26102 | date = July 2002 | pmid = 12118039 | doi = 10.1074/jbc.M204013200 | doi-access = free }}
NCOA2,{{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 = Molecular Endocrinology | volume = 15 | issue = 4 | pages = 501–511 | date = April 2001 | pmid = 11266503 | doi = 10.1210/mend.15.4.0624 | doi-access = free }}{{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 | display-authors = 6 | 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 | s2cid = 6955342 | doi-access = free }}
NCOA3,{{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 = Molecular and Cellular Biology | volume = 23 | issue = 17 | pages = 6210–6220 | date = September 2003 | pmid = 12917342 | pmc = 180928 | doi = 10.1128/MCB.23.17.6210-6220.2003 }}
POU2F1,{{cite journal | vauthors = Préfontaine GG, Walther R, Giffin W, Lemieux ME, Pope L, Haché RJ | title = Selective binding of steroid hormone receptors to octamer transcription factors determines transcriptional synergism at the mouse mammary tumor virus promoter | journal = The Journal of Biological Chemistry | volume = 274 | issue = 38 | pages = 26713–26719 | date = September 1999 | pmid = 10480874 | doi = 10.1074/jbc.274.38.26713 | doi-access = free }}{{cite journal | vauthors = Préfontaine GG, Lemieux ME, Giffin W, Schild-Poulter C, Pope L, LaCasse E, Walker P, Haché RJ | display-authors = 6 | title = Recruitment of octamer transcription factors to DNA by glucocorticoid receptor | journal = Molecular and Cellular Biology | volume = 18 | issue = 6 | pages = 3416–3430 | date = June 1998 | pmid = 9584182 | pmc = 108923 | doi = 10.1128/MCB.18.6.3416 }}
RANBP9,{{cite journal | vauthors = Rao MA, Cheng H, Quayle AN, Nishitani H, Nelson CC, Rennie PS | title = RanBPM, a nuclear protein that interacts with and regulates transcriptional activity of androgen receptor and glucocorticoid receptor | journal = The Journal of Biological Chemistry | volume = 277 | issue = 50 | pages = 48020–48027 | date = December 2002 | pmid = 12361945 | doi = 10.1074/jbc.M209741200 | doi-access = free }}
RELA,{{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 & Development | volume = 14 | issue = 18 | pages = 2314–2329 | date = September 2000 | pmid = 10995388 | pmc = 316928 | doi = 10.1101/gad.827900 }}{{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 | display-authors = 6 | title = Negative cross-talk between RelA and the glucocorticoid receptor: a possible mechanism for the antiinflammatory action of glucocorticoids | journal = Molecular Endocrinology | volume = 9 | issue = 4 | pages = 401–412 | date = April 1995 | pmid = 7659084 | doi = 10.1210/mend.9.4.7659084 | s2cid = 28680611 | doi-access = free }}
SMAD3,{{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 = The Journal of Biological Chemistry | volume = 278 | issue = 43 | pages = 41779–41788 | date = October 2003 | pmid = 12902338 | doi = 10.1074/jbc.M305350200 | s2cid = 950035 | citeseerx = 10.1.1.631.7318 | doi-access = free }}{{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 = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 21 | pages = 11776–11781 | date = October 1999 | pmid = 10518526 | pmc = 18362 | doi = 10.1073/pnas.96.21.11776 | doi-access = free | bibcode = 1999PNAS...9611776S }}
SMARCD1,
SMARCA4{{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 = Molecular and Cellular Biology | volume = 20 | issue = 6 | pages = 2004–2013 | date = March 2000 | pmid = 10688647 | pmc = 110817 | doi = 10.1128/MCB.20.6.2004-2013.2000 }}
STAT3,{{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 & Development | volume = 17 | issue = 20 | pages = 2564–2577 | date = October 2003 | pmid = 14522952 | pmc = 218150 | doi = 10.1101/gad.1135003 }}{{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 = The Journal of Biological Chemistry | volume = 272 | issue = 49 | pages = 30607–30610 | date = December 1997 | pmid = 9388192 | doi = 10.1074/jbc.272.49.30607 | doi-access = free }}
STAT5B,{{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 = 726–728 | date = October 1996 | pmid = 8878484 | doi = 10.1038/383726a0 | s2cid = 4356272 | bibcode = 1996Natur.383..726S | url = https://hal-univ-tours.archives-ouvertes.fr/hal-02427426/file/Functional%20interactions%20between%20StatS%20and%20GR.pdf }}
Thioredoxin,{{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 = The Journal of Biological Chemistry | volume = 274 | issue = 5 | pages = 3182–3188 | date = January 1999 | pmid = 9915858 | doi = 10.1074/jbc.274.5.3182 | doi-access = free }}
TRIM28,{{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 = Molecular and Cellular Biology | volume = 18 | issue = 10 | pages = 5880–5887 | date = October 1998 | pmid = 9742105 | pmc = 109174 | doi = 10.1128/mcb.18.10.5880 }} and
YWHAH.{{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 = The Journal of Biological Chemistry | volume = 272 | issue = 13 | pages = 8153–8156 | date = March 1997 | pmid = 9079630 | doi = 10.1074/jbc.272.13.8153 | doi-access = free }}

References

External links

[http://www.hprd.org/protein/00679 Human Protein Reference Database] {{Webarchive|url=https://web.archive.org/web/20060301010038/http://www.hprd.org/protein/00679 |date=2006-03-01 }}
{{MeshName|Glucocorticoid+receptors}}
{{FactorBook|GR}}
{{PDBe-KB2|P04150|Glucocorticoid receptor}}

Category:Genome projects