Abstract
In recent years, there has been a growing realization that a static two-dimensional model of gene activation by transcription factors is inadequate. Based on the work from a number of groups (Kang et al. 2002; Liu and Bagchi 2004; Metivier et al. 2003; Park et al. 2005; Reid et al. 2003; Shang et al. 2000; Sharma and Fondell 2002; Vaisanen et al. 2005), it is becoming clear that transcriptional regulation by nuclear receptors is a dynamic and cyclical process (Metivier et al. 2006). There are significant consequences that arise from this shift in understanding, from nuclear receptors as ligand activated factors that bind to a response element to activate expression of a target gene to a process where the receptor repeatedly binds in order to achieve transcription. New insights that arise from viewing the activation process as cyclical and the consequences of this for developing new strategies that modulate the activity of the estrogen receptor are outlined in this chapter.
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References
Chavez-Blanco A, Segura-Pacheco B, Perez-Cardenas E et al. (2005) Histone acetylation and histone deacetylase activity of magnesium valproate in tumor and peripheral blood of patients with cervical cancer. A phase I study. Mol Cancer 4:22
Ciechanover A (2005) Proteolysis: from the lysosome to ubiquitin and the proteasome. Nat Rev Mol Cell Biol 6:79–87
Duncan S (2001) Polycystic ovarian syndrome in women with epilepsy: a review. Epilepsia 42(Suppl 3):60–65
Flouriot G, Brand H, Denger S et al. (2000) Identification of a new isoform of the human estrogen receptor-alpha (hER-alpha) that is encoded by distinct transcripts and that is able to repress hER-alpha activation function 1. EMBO J 19:4688–4700
Isojarvi JI, Laatikainen TJ, Pakarinen AJ et al. (1993) Polycystic ovaries and hyperandrogenism in women taking valproate for epilepsy. N Engl J Med 329:1383–1388
Kang Z, Pirskanen A, Janne OA et al. (2002) Involvement of proteasome in the dynamic assembly of the androgen receptor transcription complex. J Biol Chem 277:48366–48371
Kramer OH, Zhu P, Ostendorff HP et al. (2003) The histone deacetylase inhibitor valproic acid selectively induces proteasomal degradation of HDAC2. EMBO J 22:3411--3420
Liu XF, Bagchi MK (2004) Recruitment of distinct chromatin-modifying complexes by tamoxifen-complexed estrogen receptor at natural target gene promoters in vivo. J Biol Chem 279:15050–15058
Lonard DM, Nawaz Z, Smith CL et al. (2000) The 26S proteasome is required for estrogen receptor-alpha and coactivator turnover and for efficient estrogen receptor-alpha transactivation. Mol Cell 5:939–948
Metivier R, Penot G, Hubner MR et al. (2003) Estrogen receptor-alpha directs ordered, cyclical, and combinatorial recruitment of cofactors on a natural target promoter. Cell 115:751–763
Metivier R, Penot G, Carmouche RP et al. (2004) Transcriptional complexes engaged by apo-estrogen receptor-alpha isoforms have divergent outcomes. EMBO J 23:3653–3666
Metivier R, Reid G, Gannon F (2006) Transcription in four dimensions: nuclear receptor-directed initiation of gene expression. EMBO Rep 7:161–167
Muratani M, Tansey WP (2003) How the ubiquitin-proteasome system controls transcription. Nat Rev Mol Cell Biol 4:192–201
Nawaz Z, Lonard DM, Dennis AP et al. (1999) Proteasome-dependent degradation of the human estrogen receptor. Proc Natl Acad Sci USA 96:1858–1862
Nirmala PB, Thampan RV (1995) Ubiquitination of the rat uterine estrogen receptor: dependence on estradiol. Biochem Biophys Res Commun 213:24–31
O'Donovan C, Kusumakar V, Graves GR et al. (2002) Menstrual abnormalities and polycystic ovary syndrome in women taking valproate for bipolar mood disorder. J Clin Psychiatry 63:322–330
Park KJ, Krishnan V, O'Malley BW et al. (2005) Formation of an IKKalpha-dependent transcription complex is required for estrogen receptor-mediated gene activation. Mol Cell 18:71–82
Preisler-Mashek MT, Solodin N, Stark BL et al. (2002) Ligand-specific regulation of proteasome-mediated proteolysis of estrogen receptor-alpha. Am J Physiol Endocrinol Metab 282:E891–E898
Rattya J, Pakarinen AJ, Knip M et al. (2001) Early hormonal changes during valproate or carbamazepine treatment: a 3-month study. Neurology 57:440–444
Reid G, Hubner MR, Metivier R et al. (2003) Cyclic, proteasome-mediated turnover of unliganded and liganded ERalpha on responsive promoters is an integral feature of estrogen signaling. Mol Cell 11:695–707
Reid G, Metivier R, Lin CY et al. (2005) Multiple mechanisms induce transcriptional silencing of a subset of genes, including oestrogen receptor alpha, in response to deacetylase inhibition by valproic acid and trichostatin A. Oncogene 24:4894–4907
Sato Y, Kondo I, Ishida S et al. (2001) Decreased bone mass and increased bone turnover with valproate therapy in adults with epilepsy. Neurology 57:445–449
Shang Y, Hu X, DiRenzo J et al. (2000) Cofactor dynamics and sufficiency in estrogen receptor-regulated transcription. Cell 103:843–852
Sharma D, Fondell JD (2002) Ordered recruitment of histone acetyltransferases and the TRAP/Mediator complex to thyroid hormone-responsive promoters in vivo. Proc Natl Acad Sci USA 99:7934–7939
Stenoien DL, Patel K, Mancini MG et al. (2001) FRAP reveals that mobility of oestrogen receptor-alpha is ligand- and proteasome-dependent. Nat Cell Biol 3:15–23
Teicher BA, Ara G, Herbst R et al. (1999) The proteasome inhibitor PS-341 in cancer therapy. Clin Cancer Res 5:2638–2645
Vaisanen S, Dunlop TW, Sinkkonen L et al. (2005) Spatio-temporal activation of chromatin on the human CYP24 gene promoter in the presence of 1alpha,25-Dihydroxyvitamin D3. J Mol Biol 350:65–77
Vassilev LT, Vu BT, Graves B et al. (2004) In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 303:844–848
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Johnsen, S.A., Kangaspeska, S., Reid, G., Gannon, F. (2007). Interfering with the Dynamics of Estrogen Receptor-Regulated Transcription. In: Korach, K.S., Wintermantel, T. (eds) Tissue-Specific Estrogen Action. Ernst Schering Foundation Symposium Proceedings, vol 2006/1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/2789_2006_013
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DOI: https://doi.org/10.1007/2789_2006_013
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