title: Glucocorticoid receptor cofactors as therapeutic targets.
abstract: Numerous transcriptional cofactors (e.g. coactivators, corepressors, and comodulators) are known to alter the maximal transcriptional activity (A(max)) in gene induction and repression by steroid receptors in general and glucocorticoid receptors (GRs) in particular. However, recent data advance the earlier reports that these same factors also modify other parameters of glucocorticoid receptor transcriptional activity: the potency of agonists (or EC₅₀ and the partial agonist activity of antisteroids (or PAA). In several instances, factors modulate the EC₅₀ and/or PAA without changing A(max). Thus, studies of all three parameters reveal new factors acting at various stages of receptor action, thereby increasing the potential therapeutic targets for adjusting GR actions in pathological situations.
authors.affiliation: Steroid Hormones Section, Bldg. 10, Room 8N-307B, NIDDK/CEB, National Institutes of Health (NIH), Bethesda, MD 20892-1772, USA. steroids@helix.nih.gov
authors.forename: S Stoney
authors.initials: SS
authors.lastname: Simons
mesh_terms: D000818:Animals; D002460:Cell Line; D056970:Co-Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D054333:Drug Partial Agonism; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D056918:Nuclear Receptor Coactivators / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011965:Receptors, Glucocorticoid / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D056970:Co-Repressor Proteins; D005938:Glucocorticoids; D056918:Nuclear Receptor Coactivators; D011965:Receptors, Glucocorticoid; D012097:Repressor Proteins; D014157:Transcription Factors
references.citation: Mol Endocrinol. 2004 Jun;18(6):1376-95
references.pmid: 15016838
references.citation: Proc Natl Acad Sci U S A. 2010 Apr 13;107(15):7107-12
references.pmid: 20351279
references.citation: J Biol Chem. 2005 Nov 11;280(45):37853-67
references.pmid: 16141201
references.citation: Mol Endocrinol. 2006 May;20(5):1048-60
references.pmid: 16373395
references.citation: Mol Endocrinol. 2009 Feb;23(2):213-25
references.pmid: 19074551
references.citation: Mol Endocrinol. 2007 May;21(5):1066-81
references.pmid: 17356170
references.citation: J Biol Chem. 2009 Apr 3;284(14):9099-108
references.pmid: 19211567
references.citation: Cell. 2006 Feb 10;124(3):615-29
references.pmid: 16469706
references.citation: Mol Cell. 2007 Sep 7;27(5):691-700
references.pmid: 17803935
references.citation: Mol Cell Biol. 2000 Dec;20(23):9009-17
references.pmid: 11073999
references.citation: J Med Chem. 2008 Oct 23;51(20):6512-30
references.pmid: 18785725
references.citation: Mol Cell Endocrinol. 2009 Feb 27;299(2):219-31
references.pmid: 19007848
references.citation: Mol Endocrinol. 1996 Nov;10(11):1399-406
references.pmid: 8923466
references.citation: Mol Cell Endocrinol. 2008 Feb 13;283(1-2):114-26
references.pmid: 18215457
references.citation: J Biol Chem. 2010 Jan 22;285(4):2642-52
references.pmid: 19940143
references.citation: Mol Endocrinol. 2009 Dec;23(12):1963-72
references.pmid: 19855091
references.citation: Biochemistry. 2008 Jul 22;47(29):7648-62
references.pmid: 18578507
references.citation: J Endocrinol. 2008 Sep;198(3):499-509
references.pmid: 18583474
references.citation: Trends Biochem Sci. 2004 Jun;29(6):317-24
references.pmid: 15276186
references.citation: Nucleic Acids Res. 2009 Jul;37(12):4100-15
references.pmid: 19429690
references.citation: Mol Endocrinol. 2008 Jan;22(1):33-46
references.pmid: 17885209
references.citation: J Steroid Biochem Mol Biol. 2006 Jul;100(1-3):3-17
references.pmid: 16723222
references.citation: Science. 2009 Apr 17;324(5925):407-10
references.pmid: 19372434
references.citation: BMC Cancer. 2010 Apr 07;10:128
references.pmid: 20374646
references.citation: Nature. 2007 Jul 26;448(7152):420-1
references.pmid: 17653180
references.citation: Mol Endocrinol. 2005 Jun;19(6):1529-42
references.pmid: 15802373
references.citation: Nat Struct Biol. 2002 May;9(5):359-64
references.pmid: 11953755
references.citation: Biochemistry. 2007 Jul 10;46(27):8036-49
references.pmid: 17571860
references.citation: J Biol Chem. 2009 Sep 18;284(38):25576-84
references.pmid: 19622840
references.citation: J Biol Chem. 2001 Jul 6;276(27):24806-16
references.pmid: 11333273
references.citation: Steroids. 2007 Feb;72(2):188-201
references.pmid: 17173941
references.citation: Mol Pharmacol. 2000 Jun;57(6):1206-17
references.pmid: 10825392
references.citation: Mol Endocrinol. 2010 Jan;24(1):76-90
references.pmid: 19887647
references.citation: Mol Cell Biol. 2007 Feb;27(4):1467-85
references.pmid: 17116691
references.citation: Mol Endocrinol. 1999 Dec;13(12):2108-21
references.pmid: 10598585
references.citation: Mol Endocrinol. 2004 Apr;18(4):941-52
references.pmid: 14726490
references.citation: Bioessays. 2008 Aug;30(8):744-56
references.pmid: 18623071
references.citation: Genes Dev. 2006 Jun 1;20(11):1405-28
references.pmid: 16751179
references.citation: Mol Cell Biol. 2009 Oct;29(20):5413-25
references.pmid: 19687299
references.citation: Nature. 1995 Dec 14;378(6558):681-9
references.pmid: 7501014
references.citation: Nat Rev Mol Cell Biol. 2005 Jul;6(7):542-54
references.pmid: 15957004
references.citation: Proc Natl Acad Sci U S A. 2007 Oct 9;104(41):16074-9
references.pmid: 17911242
references.citation: Mol Cell Biol. 2006 Sep;26(17):6633-55
references.pmid: 16914745
references.citation: Endocr Rev. 2007 Aug;28(5):575-87
references.pmid: 17609497
references.citation: Hum Immunol. 2009 Oct;70(10):785-9
references.pmid: 19665040
references.citation: Mol Cell Endocrinol. 2008 Nov 25;295(1-2):94-100
references.pmid: 18762230
references.citation: Cell. 2007 Jul 13;130(1):153-64
references.pmid: 17632062
references.citation: J Biol Chem. 1984 Jan 25;259(2):820-31
references.pmid: 6693398
references.citation: J Med Chem. 2009 Jul 9;52(13):3892-901
references.pmid: 19469546
references.citation: FEBS Lett. 2009 May 6;583(9):1493-8
references.pmid: 19375531
references.citation: Mol Cell Biol. 2010 Mar;30(5):1243-53
references.pmid: 20048054
references.citation: Proc Natl Acad Sci U S A. 2007 Feb 13;104(7):2187-92
references.pmid: 17277083
references.citation: Mol Endocrinol. 2005 Feb;19(2):290-311
references.pmid: 15539428
references.citation: J Exp Med. 2006 Jan 23;203(1):7-13
references.pmid: 16380507
references.citation: J Biol Chem. 2009 Dec 25;284(52):36395-36404
references.pmid: 19858209
references.citation: J Exp Med. 2004 Apr 19;199(8):1163-74
references.pmid: 15096541
references.citation: Mol Endocrinol. 2008 Aug;22(8):1754-66
references.pmid: 18483179
references.citation: Curr Top Med Chem. 2006;6(3):271-85
references.pmid: 16515481
references.citation: Biochemistry. 2006 Jun 13;45(23):7299-306
references.pmid: 16752918
references.citation: Mol Endocrinol. 2009 Apr;23(4):572-83
references.pmid: 19164447