Home LiteratureArticle Details
PMID: 17636311 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Interaction of estrogen receptor alpha with proliferating cell nuclear antigen.

Nucleic acids research ·Vol. 35 ·No. 15 ·2007-00-00 ·Pages 5028-38

Schultz-Norton JR, Gabisi VA, Ziegler YS, McLeod IX, Yates JR, Nardulli AM

Abstract

The ability of estrogen receptor alpha (ERalpha) to modulate gene expression is influenced by the recruitment of a host of co-regulatory proteins to target genes. To further understand how estrogen-responsive genes are regulated, we have isolated and identified proteins associated with ERalpha when it is bound to DNA containing the consensus estrogen response element (ERE). One of the proteins identified in this complex, proliferating cell nuclear antigen (PCNA), is required for DNA replication and repair. We show that PCNA interacts with ERalpha in the absence and in the presence of DNA, enhances the interaction of ERalpha with ERE-containing DNA, and associates with endogenous estrogen-responsive genes. Interestingly, rather than altering hormone responsiveness of endogenous, estrogen-responsive genes, PCNA increases the basal expression of these genes. Our studies suggest that in addition to serving as a platform for the recruitment of DNA replication and repair proteins, PCNA may serve as a platform for transcription factors involved in regulating gene expression.

MeSH Terms
Cell Line, Tumor Estradiol/pharmacology Estrogen Receptor alpha/metabolism Humans Proliferating Cell Nuclear Antigen/isolation & purification,metabolism Response Elements Transcription, Genetic/drug effects
Chemicals
Estrogen Receptor alpha Proliferating Cell Nuclear Antigen Estradiol
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Schultz-Norton Jennifer R
Department of Molecular and Integrative Physiology, University of Illinois, Urbana, IL 61801, USA.
Gabisi Vivian A
Ziegler Yvonne S
McLeod Ian X
Yates John R
Nardulli Ann M
References (94)
94 references, click to expand
  1. The discovery of labile methyl esters on proliferating cell nuclear antigen by MS/MS.
    Proteomics. 2006 Sep;6(17):4808-16 PMID: 16888766
  2. Structure of the progesterone receptor-deoxyribonucleic acid complex: novel interactions required for binding to half-site response elements.
    Mol Endocrinol. 2006 Dec;20(12):3042-52 PMID: 16931575
  3. Proliferating cell nuclear antigen loaded onto double-stranded DNA: dynamics, minor groove interactions and functional implications.
    Nucleic Acids Res. 2006;34(20):6023-33 PMID: 17071716
  4. A cancer-associated PCNA expressed in breast cancer has implications as a potential biomarker.
    Proc Natl Acad Sci U S A. 2006 Dec 19;103(51):19472-7 PMID: 17159154
  5. The deoxyribonucleic acid repair protein flap endonuclease-1 modulates estrogen-responsive gene expression.
    Mol Endocrinol. 2007 Jul;21(7):1569-80 PMID: 17488975
  6. Proliferating cell nuclear antigen (PCNA): a dancer with many partners.
    J Cell Sci. 2003 Aug 1;116(Pt 15):3051-60 PMID: 12829735
  7. Profiling of estrogen up- and down-regulated gene expression in human breast cancer cells: insights into gene networks and pathways underlying estrogenic control of proliferation and cell phenotype.
    Endocrinology. 2003 Oct;144(10):4562-74 PMID: 12959972
  8. The human proliferating Cell nuclear antigen regulates transcriptional coactivator p300 activity and promotes transcriptional repression.
    J Biol Chem. 2003 Nov 7;278(45):44505-13 PMID: 12937166
  9. Estrogen receptor-alpha directs ordered, cyclical, and combinatorial recruitment of cofactors on a natural target promoter.
    Cell. 2003 Dec 12;115(6):751-63 PMID: 14675539
  10. Selective estrogen receptor modulators: discrimination of agonistic versus antagonistic activities by gene expression profiling in breast cancer cells.
    Cancer Res. 2004 Feb 15;64(4):1522-33 PMID: 14973112
  11. Fos and Jun inhibit estrogen-induced transcription of the human progesterone receptor gene through an activator protein-1 site.
    Mol Endocrinol. 2004 Mar;18(3):521-32 PMID: 14684847
  12. The role of the C-terminal extension (CTE) of the estrogen receptor alpha and beta DNA binding domain in DNA binding and interaction with HMGB.
    J Biol Chem. 2004 Apr 9;279(15):14763-71 PMID: 14739282
  13. Interaction of estrogen receptor alpha with 3-methyladenine DNA glycosylase modulates transcription and DNA repair.
    J Biol Chem. 2004 Apr 16;279(16):16875-82 PMID: 14761960
  14. Differential regulation of the human progesterone receptor gene through an estrogen response element half site and Sp1 sites.
    J Steroid Biochem Mol Biol. 2004 Feb;88(2):113-22 PMID: 15084343
  15. Transcriptional activation of genes by 17 beta-estradiol through estrogen receptor-Sp1 interactions.
    Vitam Horm. 2001;62:231-52 PMID: 11345900
  16. The N-terminal region of human progesterone B-receptors: biophysical and biochemical comparison to A-receptors.
    J Biol Chem. 2001 Jun 29;276(26):23825-31 PMID: 11328821
  17. Allosteric modulation of estrogen receptor conformation by different estrogen response elements.
    Mol Endocrinol. 2001 Jul;15(7):1114-26 PMID: 11435612
  18. Interaction of estrogen receptors alpha and beta with estrogen response elements.
    Mol Cell Endocrinol. 2001 Jul 5;181(1-2):151-63 PMID: 11476949
  19. Global gene expression analysis to identify molecular markers of uterine receptivity and embryo implantation.
    J Biol Chem. 2001 Nov 23;276(47):44137-45 PMID: 11551965
  20. Differential modulation of DNA conformation by estrogen receptors alpha and beta.
    J Biol Chem. 2002 Mar 8;277(10):8702-7 PMID: 11773069
  21. Allosteric regulation of estrogen receptor structure, function, and coactivator recruitment by different estrogen response elements.
    Mol Endocrinol. 2002 Mar;16(3):469-86 PMID: 11875105
  22. A new vector for high-throughput, ligation-independent cloning encoding a tobacco etch virus protease cleavage site.
    Protein Expr Purif. 2002 Jun;25(1):8-15 PMID: 12071693
  23. The C-terminal extension (CTE) of the nuclear hormone receptor DNA binding domain determines interactions and functional response to the HMGB-1/-2 co-regulatory proteins.
    J Biol Chem. 2002 Jul 12;277(28):25115-24 PMID: 12006575
  24. Estrogen receptor alpha and activating protein-1 mediate estrogen responsiveness of the progesterone receptor gene in MCF-7 breast cancer cells.
    Endocrinology. 2002 Dec;143(12):4583-91 PMID: 12446585
  25. Transfer of the MSH2.MSH6 complex from proliferating cell nuclear antigen to mispaired bases in DNA.
    J Biol Chem. 2003 Jan 3;278(1):14-7 PMID: 12435741
  26. A novel estrogen receptor alpha-associated protein, template-activating factor Ibeta, inhibits acetylation and transactivation.
    Mol Endocrinol. 2003 Jan;17(1):67-78 PMID: 12511607
  27. Estrogen receptor alpha and Sp1 regulate progesterone receptor gene expression.
    Mol Cell Endocrinol. 2003 Mar 28;201(1-2):165-75 PMID: 12706304
  28. Preparation and crystallization of human flap endonuclease FEN-1 in complex with proliferating-cell nuclear antigen, PCNA.
    Acta Crystallogr D Biol Crystallogr. 2003 May;59(Pt 5):933-5 PMID: 12777816
  29. Sequence and characterization of a coactivator for the steroid hormone receptor superfamily.
    Science. 1995 Nov 24;270(5240):1354-7 PMID: 7481822
  30. The high mobility group protein 1 enhances binding of the estrogen receptor DNA binding domain to the estrogen response element.
    Mol Endocrinol. 1998 May;12(5):664-74 PMID: 9605929
  31. High mobility of flap endonuclease 1 and DNA polymerase eta associated with replication foci in mammalian S-phase nucleus.
    Mol Biol Cell. 2005 May;16(5):2518-28 PMID: 15758026
  32. PCNA acts as a stationary loading platform for transiently interacting Okazaki fragment maturation proteins.
    Nucleic Acids Res. 2005;33(11):3521-8 PMID: 15972794
  33. The proliferating cell nuclear antigen regulates retinoic acid receptor transcriptional activity through direct protein-protein interaction.
    Nucleic Acids Res. 2005;33(13):4311-21 PMID: 16055921
  34. Location of cell cycle regulators cyclin B1, cyclin A, PCNA, Ki67 and cell cycle inhibitors p21, p27 and p57 in human first trimester placenta and deciduas.
    Histochem Cell Biol. 2006 Jun;125(6):615-24 PMID: 16491347
  35. A novel estrogen receptor alpha-associated protein alters receptor-deoxyribonucleic acid interactions and represses receptor-mediated transcription.
    Mol Endocrinol. 2004 Nov;18(11):2649-59 PMID: 15308690
  36. Autoantibody to a nuclear antigen in proliferating cells.
    J Immunol. 1978 Dec;121(6):2228-34 PMID: 102692
  37. Characterization of the estrogen receptor and its dynamics in MCF-7 human breast cancer cells using a covalently attaching antiestrogen.
    Endocrinology. 1984 Jul;115(1):143-53 PMID: 6734512
  38. Functional domains of the human estrogen receptor.
    Cell. 1987 Dec 24;51(6):941-51 PMID: 3690665
  39. Gene regulation by steroid hormones.
    Cell. 1989 Feb 10;56(3):335-44 PMID: 2644044
  40. The human estrogen receptor has two independent nonacidic transcriptional activation functions.
    Cell. 1989 Nov 3;59(3):477-87 PMID: 2805068
  41. Identification of a conserved region required for hormone dependent transcriptional activation by steroid hormone receptors.
    EMBO J. 1992 Mar;11(3):1025-33 PMID: 1372244
  42. Proliferating cell nuclear antigen is required for DNA excision repair.
    Cell. 1992 Apr 17;69(2):367-74 PMID: 1348971
  43. Proliferating-cell nuclear antigen (PC10) immunolabelling and other proliferation indices as prognostic factors in breast cancer.
    J Cancer Res Clin Oncol. 1993;119(5):288-94 PMID: 8095051
  44. Different TBP-associated factors are required for mediating the stimulation of transcription in vitro by the acidic transactivator GAL-VP16 and the two nonacidic activation functions of the estrogen receptor.
    Nucleic Acids Res. 1993 Jan 11;21(1):5-12 PMID: 8441620
  45. Defining a minimal estrogen receptor DNA binding domain.
    Nucleic Acids Res. 1993 Mar 11;21(5):1125-32 PMID: 8385312
  46. Proliferating cell nuclear antigen immunohistochemistry using monoclonal antibody 19A2 and a new antigen retrieval technique has prognostic impact in archival paraffin-embedded node-negative breast cancer.
    Am J Pathol. 1993 Apr;142(4):1081-9 PMID: 7682759
  47. Proliferating cell nuclear antigen (PCNA) immunolabeling as a prognostic factor in axillary lymph node negative breast cancer.
    Anticancer Res. 1993 Mar-Apr;13(2):533-8 PMID: 8100128
  48. Differential recognition of target genes by nuclear receptor monomers, dimers, and heterodimers.
    Endocr Rev. 1994 Jun;15(3):391-407 PMID: 8076589
  49. Insights from the study of animals lacking functional estrogen receptor.
    Science. 1994 Dec 2;266(5190):1524-7 PMID: 7985022
  50. Crystal structure of the eukaryotic DNA polymerase processivity factor PCNA.
    Cell. 1994 Dec 30;79(7):1233-43 PMID: 8001157
  51. Intrinsically bent DNA in a eukaryotic transcription factor recognition sequence potentiates transcription activation.
    J Biol Chem. 1995 Jan 20;270(3):1282-8 PMID: 7836392
  52. The interaction of human estrogen receptor with DNA is modulated by receptor-associated proteins.
    Mol Endocrinol. 1994 Oct;8(10):1407-19 PMID: 7854357
  53. Characterization of the amino-terminal transcriptional activation function of the human estrogen receptor in animal and yeast cells.
    J Biol Chem. 1995 Apr 21;270(16):9535-42 PMID: 7721882
  54. Structural and functional similarities of prokaryotic and eukaryotic DNA polymerase sliding clamps.
    Nucleic Acids Res. 1995 Sep 25;23(18):3613-20 PMID: 7478986
  55. Estrogen receptor-induced DNA bending: orientation of the bend and replacement of an estrogen response element with an intrinsic DNA bending sequence.
    Mol Endocrinol. 1995 Aug;9(8):1064-76 PMID: 7476980
  56. Detection of nucleotide excision repair incisions in human fibroblasts by immunostaining for PCNA.
    Exp Cell Res. 1995 Dec;221(2):326-32 PMID: 7493631
  57. Escherichia coli expression vectors containing a protein kinase recognition motif, His6-tag and hemagglutinin epitope.
    Gene. 1995 Dec 1;166(1):177-8 PMID: 8529886
  58. Subcellular distribution of p21 and PCNA in normal and repair-deficient cells following DNA damage.
    Curr Biol. 1996 Feb 1;6(2):189-99 PMID: 8673466
  59. Role of CBP/P300 in nuclear receptor signalling.
    Nature. 1996 Sep 5;383(6595):99-103 PMID: 8779723
  60. p300 is a component of an estrogen receptor coactivator complex.
    Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11540-5 PMID: 8876171
  61. Nuclear receptor coactivators and corepressors.
    Mol Endocrinol. 1996 Oct;10(10):1167-77 PMID: 9121485
  62. GRIP1, a transcriptional coactivator for the AF-2 transactivation domain of steroid, thyroid, retinoid, and vitamin D receptors.
    Mol Cell Biol. 1997 May;17(5):2735-44 PMID: 9111344
  63. RAC3, a steroid/nuclear receptor-associated coactivator that is related to SRC-1 and TIF2.
    Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8479-84 PMID: 9238002
  64. AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer.
    Science. 1997 Aug 15;277(5328):965-8 PMID: 9252329
  65. Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300.
    Cell. 1997 Aug 8;90(3):569-80 PMID: 9267036
  66. A role for oestrogens in the male reproductive system.
    Nature. 1997 Dec 4;390(6659):509-12 PMID: 9393999
  67. Altered ligand binding properties and enhanced stability of a constitutively active estrogen receptor: evidence that an open pocket conformation is required for ligand interaction.
    Biochemistry. 1997 Dec 2;36(48):14897-905 PMID: 9398213
  68. p300 and estrogen receptor cooperatively activate transcription via differential enhancement of initiation and reinitiation.
    Genes Dev. 1998 Feb 1;12(3):331-42 PMID: 9450928
  69. Estrogen response elements function as allosteric modulators of estrogen receptor conformation.
    Mol Cell Biol. 1998 Apr;18(4):1927-34 PMID: 9528764
  70. Long-term prognostic value of PCNA labeling index in primary operable breast cancer.
    Oncol Rep. 1998 May-Jun;5(3):641-4 PMID: 9538167
  71. Expression of proliferating cell nuclear antigen (PCNA) and apoptosis related antigen (LeY) in epithelial skin tumors.
    Am J Dermatopathol. 1998 Apr;20(2):164-9 PMID: 9557786
  72. [Expression and clinical significance of PCNA in renal pelvic and ureteral cancer].
    Zhonghua Wai Ke Za Zhi. 1996 Oct;34(10):614-6 PMID: 9590738
  73. The Werner syndrome gene product co-purifies with the DNA replication complex and interacts with PCNA and topoisomerase I.
    J Biol Chem. 1999 Dec 31;274(53):37795-9 PMID: 10608841
  74. DNA polymerase switching: I. Replication factor C displaces DNA polymerase alpha prior to PCNA loading.
    J Mol Biol. 2000 Jan 28;295(4):791-801 PMID: 10656791
  75. The N-terminal region of the human progesterone A-receptor. Structural analysis and the influence of the DNA binding domain.
    J Biol Chem. 2000 Mar 10;275(10):7313-20 PMID: 10702302
  76. Nuclear hormone receptor coregulators in action: diversity for shared tasks.
    Mol Endocrinol. 2000 Mar;14(3):329-47 PMID: 10707952
  77. Mechanism whereby proliferating cell nuclear antigen stimulates flap endonuclease 1.
    J Biol Chem. 2000 Apr 7;275(14):10498-505 PMID: 10744741
  78. Gene expression of flap endonuclease-1 during cell proliferation and differentiation.
    Biochim Biophys Acta. 2000 Apr 17;1496(2-3):333-40 PMID: 10771101
  79. Sp1 binding sites and an estrogen response element half-site are involved in regulation of the human progesterone receptor A promoter.
    Mol Endocrinol. 2000 Jul;14(7):972-85 PMID: 10894148
  80. Analysis of estrogen receptor interaction with a repressor of estrogen receptor activity (REA) and the regulation of estrogen receptor transcriptional activity by REA.
    J Biol Chem. 2000 Nov 17;275(46):35848-56 PMID: 10960470
  81. Cofactor dynamics and sufficiency in estrogen receptor-regulated transcription.
    Cell. 2000 Dec 8;103(6):843-52 PMID: 11136970
  82. Regulation of the estrogen-responsive pS2 gene in MCF-7 human breast cancer cells.
    J Steroid Biochem Mol Biol. 2000 Nov 15;74(4):157-68 PMID: 11162921
  83. High-mobility group chromatin proteins 1 and 2 functionally interact with steroid hormone receptors to enhance their DNA binding in vitro and transcriptional activity in mammalian cells.
    Mol Cell Biol. 1998 Aug;18(8):4471-87 PMID: 9671457
  84. Structure of the DNA repair and replication endonuclease and exonuclease FEN-1: coupling DNA and PCNA binding to FEN-1 activity.
    Cell. 1998 Oct 2;95(1):135-46 PMID: 9778254
  85. Proliferating cell nuclear antigen (PCNA) immunolabeling as a prognostic factor in invasive ductal carcinoma of the breast in Taiwan.
    Cancer Lett. 1998 Sep 25;131(2):145-52 PMID: 9851246
  86. Proliferating cell nuclear antigen facilitates excision in long-patch base excision repair.
    J Biol Chem. 1999 Feb 12;274(7):4354-63 PMID: 9933638
  87. An estrogen receptor-selective coregulator that potentiates the effectiveness of antiestrogens and represses the activity of estrogens.
    Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):6947-52 PMID: 10359819
  88. Interdomain signaling in a two-domain fragment of the human glucocorticoid receptor.
    J Biol Chem. 1999 Aug 27;274(35):24737-41 PMID: 10455143
  89. Regulation of hormone-induced histone hyperacetylation and gene activation via acetylation of an acetylase.
    Cell. 1999 Sep 3;98(5):675-86 PMID: 10490106
  90. Estrogen response element-dependent regulation of transcriptional activation of estrogen receptors alpha and beta by coactivators and corepressors.
    J Mol Endocrinol. 2004 Oct;33(2):387-410 PMID: 15525597
  91. Cell- and ligand-specific regulation of promoters containing activator protein-1 and Sp1 sites by estrogen receptors alpha and beta.
    J Biol Chem. 2005 Jan 7;280(1):347-54 PMID: 15509581
  92. Structural basis for recruitment of human flap endonuclease 1 to PCNA.
    EMBO J. 2005 Feb 23;24(4):683-93 PMID: 15616578
  93. Acetylation of estrogen receptor alpha by p300 at lysines 266 and 268 enhances the deoxyribonucleic acid binding and transactivation activities of the receptor.
    Mol Endocrinol. 2006 Jul;20(7):1479-93 PMID: 16497729
  94. Protein disulfide isomerase serves as a molecular chaperone to maintain estrogen receptor alpha structure and function.
    Mol Endocrinol. 2006 Sep;20(9):1982-95 PMID: 16690750
Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gkm533
Published
2007-00-00
Epub
2007-00-18
Pages
5028-38
Language
English
Region
England
NLM ID
0411011
PMCID
PMC1976446
Subset
IM
Grants
NIDDK NIH HHS · R01 DK053884-09 · United States
NIDDK NIH HHS · R01 DK053884 · United States
NICHD NIH HHS · T32 HD07028 · United States
NIDDK NIH HHS · R01 DK 53884 · United States
NCRR NIH HHS · P41 RR011823 · United States
NCRR NIH HHS · P41 RR11823-10 · United States
NICHD NIH HHS · T32 HD007028 · United States
External Links
PubMed source DOI: 10.1093/nar/gkm533 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2