title: Non-classical genomic estrogen receptor (ER)/specificity protein and ER/activating protein-1 signaling pathways.
abstract: 17beta-estradiol binds to the estrogen receptor (ER) to activate gene expression or repression and this involves both genomic (nuclear) and non-genomic (extranuclear) pathways. Genomic pathways include the classical interactions of ligand-bound ER dimers with estrogen-responsive elements in target gene promoters. ER-dependent activation of gene expression also involves DNA-bound ER that subsequently interacts with other DNA-bound transcriptions factors and direct ER-transcription factor (protein-protein) interactions where ER does not bind promoter DNA. Ligand-induced activation of ER/specificity protein (Sp) and ER/activating protein-1 [(AP-1); consisting of jun/fos] complexes are important pathways for modulating expression of a large number of genes. This review summarizes some of the characteristics of ER/Sp- and ER/AP-1-mediated transactivation, which are dependent on ligand structure, cell context, ER-subtype (ERalpha and ERbeta), and Sp protein (SP1, SP3, and SP4) and demonstrates that this non-classical genomic pathway is also functional in vivo.
authors.affiliation: Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, Texas 77843-4466, USA. ssafe@cvm.tamu.edu
authors.forename: Stephen
authors.initials: S
authors.lastname: Safe
authors.forename: Kyounghyun
authors.initials: K
authors.lastname: Kim
authors.forename: Kyoungkim
authors.initials: K
authors.lastname: Kim
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004958:Estradiol / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D008024:Ligands; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D008024:Ligands; D011960:Receptors, Estrogen; D016329:Sp1 Transcription Factor; D018808:Transcription Factor AP-1; D004958:Estradiol
references.citation: Proc Natl Acad Sci U S A. 2007 May 8;104(19):8173-7
references.pmid: 17470805
references.citation: Endocrinology. 2006 Feb;147(2):899-911
references.pmid: 16254027
references.citation: J Steroid Biochem Mol Biol. 2004 Jan;88(1):53-9
references.pmid: 15026083
references.citation: Endocrinology. 2000 Jul;141(7):2439-49
references.pmid: 10875244
references.citation: Endocrinology. 1999 Jun;140(6):2501-8
references.pmid: 10342835
references.citation: Endocrinology. 2000 Jun;141(6):2266-74
references.pmid: 10830317
references.citation: Mol Endocrinol. 2006 Aug;20(8):1707-14
references.pmid: 16396959
references.citation: Arch Biochem Biophys. 2007 May 15;461(2):200-10
references.pmid: 17306756
references.citation: Mol Endocrinol. 2000 May;14(5):753-60
references.pmid: 10809237
references.citation: Endocrinology. 2003 Jun;144(6):2325-35
references.pmid: 12746293
references.citation: J Biol Chem. 2005 Jan 7;280(1):347-54
references.pmid: 15509581
references.citation: J Mol Endocrinol. 2005 Feb;34(1):77-89
references.pmid: 15691879
references.citation: J Biol Chem. 1992 Sep 5;267(25):17944-8
references.pmid: 1381357
references.citation: Endocrinology. 2001 Mar;142(3):1000-8
references.pmid: 11181512
references.citation: Mol Endocrinol. 1994 Jun;8(6):693-703
references.pmid: 7935485
references.citation: Mol Endocrinol. 2008 Jan;22(1):10-22
references.pmid: 17901129
references.citation: J Mol Endocrinol. 2007 Oct;39(4):289-304
references.pmid: 17909268
references.citation: Nucleic Acids Res. 1999 Aug 1;27(15):2991-3000
references.pmid: 10454592
references.citation: Cancer Res. 2001 May 15;61(10):4143-54
references.pmid: 11358838
references.citation: Science. 1986 Oct 3;234(4772):47-52
references.pmid: 3529394
references.citation: Mol Endocrinol. 2004 Dec;18(12):2937-49
references.pmid: 15358836
references.citation: Biochem J. 2000 Dec 15;352 Pt 3:763-72
references.pmid: 11104684
references.citation: Mol Cell Endocrinol. 2002 Sep 30;195(1-2):27-38
references.pmid: 12354670
references.citation: Eur J Cancer. 2005 Nov;41(16):2438-48
references.pmid: 16209919
references.citation: Vitam Horm. 2001;62:231-52
references.pmid: 11345900
references.citation: Clin Cancer Res. 2004 Jun 15;10(12 Pt 1):4109-17
references.pmid: 15217947
references.citation: J Clin Endocrinol Metab. 2007 May;92(5):1920-6
references.pmid: 17311863
references.citation: Endocrinology. 2007 Nov;148(11):5288-94
references.pmid: 17673514
references.citation: J Steroid Biochem Mol Biol. 2000 Nov 30;74(5):311-7
references.pmid: 11162939
references.citation: Endocrinology. 1998 Apr;139(4):1981-90
references.pmid: 9528985
references.citation: Mol Endocrinol. 2003 Dec;17(12):2613-29
references.pmid: 12947046
references.citation: J Biol Chem. 2007 Sep 14;282(37):27478-27492
references.pmid: 17635926
references.citation: J Biol Chem. 1998 Feb 20;273(8):4360-6
references.pmid: 9468485
references.citation: Endocrinology. 2007 Oct;148(10):4821-8
references.pmid: 17656465
references.citation: J Steroid Biochem Mol Biol. 2008 May;110(1-2):104-15
references.pmid: 18400491
references.citation: Nat Genet. 2006 Nov;38(11):1289-97
references.pmid: 17013392
references.citation: J Biol Chem. 2006 Jul 7;281(27):18825-36
references.pmid: 16651265
references.citation: Exp Cell Res. 2005 Jan 1;302(1):96-107
references.pmid: 15541729
references.citation: Science. 1997 Sep 5;277(5331):1508-10
references.pmid: 9278514
references.citation: Endocrinology. 2003 Nov;144(11):4894-904
references.pmid: 12960079
references.citation: Genomics. 2005 May;85(5):551-6
references.pmid: 15820306
references.citation: Mol Cell Endocrinol. 2003 Mar 28;201(1-2):165-75
references.pmid: 12706304
references.citation: Cancer Res. 2005 Feb 1;65(3):1007-17
references.pmid: 15705902
references.citation: Clin Cancer Res. 2006 Nov 1;12(21):6395-402
references.pmid: 17085651
references.citation: J Biol Chem. 2001 Apr 27;276(17):13615-21
references.pmid: 11278408
references.citation: J Biol Chem. 2000 Feb 25;275(8):5379-87
references.pmid: 10681512
references.citation: Mol Cell Biol. 2007 Jul;27(14):5090-104
references.pmid: 17515612
references.citation: Mol Cell Biol. 1995 Dec;15(12):6710-9
references.pmid: 8524236
references.citation: Mol Endocrinol. 2003 Feb;17(2):287-99
references.pmid: 12554755
references.citation: Endocrinology. 2005 Feb;146(2):760-8
references.pmid: 15528301
references.citation: J Cell Physiol. 2001 Aug;188(2):143-60
references.pmid: 11424081
references.citation: J Biol Chem. 1994 Jun 10;269(23):16433-42
references.pmid: 8206951
references.citation: Endocrinology. 2001 Aug;142(8):3493-501
references.pmid: 11459795
references.citation: PLoS Genet. 2007 Jun;3(6):e87
references.pmid: 17542648
references.citation: EMBO J. 1991 Dec;10(12):3839-49
references.pmid: 1935903
references.citation: Oncogene. 1992 Aug;7(8):1587-94
references.pmid: 1630819
references.citation: Endocrinology. 2007 Apr;148(4):1902-10
references.pmid: 17204553
references.citation: Endocrinology. 2002 Dec;143(12):4583-91
references.pmid: 12446585
references.citation: Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):203-7
references.pmid: 8419924
references.citation: Endocrinology. 2000 Aug;141(8):2829-36
references.pmid: 10919269
references.citation: J Biol Chem. 1994 Nov 18;269(46):28955-62
references.pmid: 7961858
references.citation: J Biol Chem. 2002 Jan 18;277(3):1669-79
references.pmid: 11700319
references.citation: J Biol Chem. 1993 Jul 5;268(19):14103-8
references.pmid: 8314777
references.citation: Endocrinology. 1999 Jan;140(1):219-27
references.pmid: 9886828
references.citation: Cell. 1990 Dec 21;63(6):1267-76
references.pmid: 2124518
references.citation: J Endocrinol. 2006 Dec;191(3):605-12
references.pmid: 17170218
references.citation: Mol Endocrinol. 1997 Oct;11(11):1569-80
references.pmid: 9328340
references.citation: Mol Endocrinol. 1991 Dec;5(12):1983-92
references.pmid: 1791843
references.citation: Mol Endocrinol. 2005 Apr;19(4):843-54
references.pmid: 15637147
references.citation: Prog Nucleic Acid Res Mol Biol. 2004;77:1-36
references.pmid: 15196889
references.citation: Biochem Biophys Res Commun. 2007 Feb 2;353(1):86-91
references.pmid: 17161377
references.citation: Oncogene. 2003 Jul 31;22(31):4875-81
references.pmid: 12894229
references.citation: BMC Cancer. 2002 Dec 10;2:35
references.pmid: 12475396
references.citation: Mol Endocrinol. 2001 Nov;15(11):1906-17
references.pmid: 11682622
references.citation: Biochem Biophys Res Commun. 2003 Apr 4;303(2):660-8
references.pmid: 12659870
references.citation: Endocrinology. 2006 Jul;147(7):3285-95
references.pmid: 16574784
references.citation: Cancer Res. 2003 Jun 1;63(11):2820-8
references.pmid: 12782587
references.citation: J Biol Chem. 2001 Aug 17;276(33):30853-61
references.pmid: 11410592
references.citation: Mol Endocrinol. 1999 Oct;13(10):1672-85
references.pmid: 10517669
references.citation: Nature. 1985 Aug 29-Sep 4;316(6031):774-8
references.pmid: 4041012
references.citation: EMBO J. 1991 Aug;10(8):2237-45
references.pmid: 1906001
references.citation: J Biol Chem. 2001 Apr 13;276(15):11590-8
references.pmid: 11145955
references.citation: J Biol Chem. 1994 Jun 3;269(22):15912-7
references.pmid: 8195246
references.citation: Mol Endocrinol. 2003 May;17(5):804-17
references.pmid: 12576490
references.citation: J Steroid Biochem Mol Biol. 2008 Jun;110(3-5):197-206
references.pmid: 18508261
references.citation: Mol Endocrinol. 2007 Jul;21(7):1617-29
references.pmid: 17456793
references.citation: Mol Endocrinol. 2008 Feb;22(2):388-402
references.pmid: 18006642
references.citation: J Biol Chem. 2001 Feb 9;276(6):3827-32
references.pmid: 11060287
references.citation: Dev Biol. 1996 Jun 15;176(2):284-99
references.pmid: 8660867
references.citation: J Biol Chem. 2004 Apr 2;279(14):13911-24
references.pmid: 14726517
references.citation: Cancer Res. 2000 Mar 15;60(6):1546-51
references.pmid: 10749121
references.citation: Mol Endocrinol. 1998 Jun;12(6):882-90
references.pmid: 9626663
references.citation: J Biol Chem. 2006 Sep 8;281(36):26683-92
references.pmid: 16847062
references.citation: Cell. 1997 May 16;89(4):619-28
references.pmid: 9160753
references.citation: Mol Endocrinol. 2000 Jul;14(7):972-85
references.pmid: 10894148
references.citation: J Biol Chem. 2000 Aug 18;275(33):25781-90
references.pmid: 10829018
references.citation: Mol Pharmacol. 2002 Jun;61(6):1273-83
references.pmid: 12021387
references.citation: Mech Dev. 2001 Aug;106(1-2):77-83
references.pmid: 11472836
references.citation: Chem Biol. 2001 May;8(5):427-36
references.pmid: 11358690
references.citation: Clin Cancer Res. 2003 Dec 15;9(17):6371-80
references.pmid: 14695137
references.citation: Mol Endocrinol. 2005 Feb;19(2):362-78
references.pmid: 15514030
references.citation: Mol Endocrinol. 1995 Apr;9(4):443-56
references.pmid: 7659088
references.citation: Mol Cell Endocrinol. 2008 Jan 16;281(1-2):9-18
references.pmid: 18022314
references.citation: J Biol Chem. 2002 Dec 13;277(50):48479-83
references.pmid: 12411447
references.citation: Mol Cell Endocrinol. 2005 Dec 21;245(1-2):53-9
references.pmid: 16298037
references.citation: Oncogene. 2004 Feb 5;23(5):1052-63
references.pmid: 14647449
references.citation: Mol Endocrinol. 1990 Nov;4(11):1720-6
references.pmid: 2126340
references.citation: J Biol Chem. 1997 Jul 18;272(29):18250-60
references.pmid: 9218463
references.citation: Mol Endocrinol. 1999 Aug;13(8):1373-87
references.pmid: 10446910
references.citation: Mol Endocrinol. 2002 Oct;16(10):2188-201
references.pmid: 12351685
references.citation: Cell Growth Differ. 1996 Mar;7(3):351-9
references.pmid: 8838865
references.citation: Cell. 1983 Nov;35(1):79-87
references.pmid: 6313230
references.citation: Mol Endocrinol. 1996 Nov;10(11):1371-8
references.pmid: 8923463
references.citation: Cancer Res. 2007 Nov 15;67(22):11001-11
references.pmid: 18006846
references.citation: Int J Oncol. 2004 Aug;25(2):461-8
references.pmid: 15254745
references.citation: Genes Cells. 2001 Aug;6(8):689-97
references.pmid: 11532028
references.citation: J Biol Chem. 1998 Apr 24;273(17):10696-701
references.pmid: 9553133
references.citation: J Biol Chem. 1999 Nov 5;274(45):32099-107
references.pmid: 10542244
references.citation: J Cell Biochem. 2001;84(1):156-72
references.pmid: 11746525
references.citation: Endocrinology. 2003 May;144(5):1675-85
references.pmid: 12697671
references.citation: J Mol Endocrinol. 2000 Jun;24(3):329-38
references.pmid: 10828826
references.citation: J Biol Chem. 2000 Jul 28;275(30):22769-79
references.pmid: 10816575
references.citation: Endocrinology. 1999 Jun;140(6):2517-25
references.pmid: 10342837
references.citation: Biochem Biophys Res Commun. 2002 Jun 7;294(2):384-94
references.pmid: 12051724
references.citation: Genome Biol. 2006;7(9):R82
references.pmid: 16961928
references.citation: Gynecol Oncol. 2006 Nov;103(2):417-24
references.pmid: 16690106