HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Langlois, M.-F. Articles by Wondisford, F. E. Search for Related Content PubMed PubMed Citation Articles by Langlois, M.-F. Articles by Wondisford, F. E. Social Bookmarking                      What's this?

Volume 272, Number 40, Issue of October 3, 1997 pp. 24927-24933
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

A Unique Role of the -2 Thyroid Hormone Receptor Isoform in Negative Regulation by Thyroid Hormone
MAPPING OF A NOVEL AMINO-TERMINAL DOMAIN IMPORTANT FOR LIGAND-INDEPENDENT ACTIVATION

(Received for publication, April 25, 1997, and in revised form, July 28, 1997)

From the Thyroid Unit, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215

Negative regulation by thyroid hormone is mediated by nuclear thyroid hormone receptors (TRs) acting on thyroid hormone response elements (TREs). We examine here the role of human TR-2, a TR isoform with central nervous system-restricted expression, in the regulation of target genes whose expression are decreased by triiodothyronine (T₃). Using transient transfection studies, we found that TR-2 achieved significantly greater ligand-independent activation on the thyrotropin-releasing hormone (TRH) and common glycoprotein -subunit genes than either TR-1 or TR-1. A chimeric TR- isoform containing the TR-2 amino terminus linked to the TR-1 DNA- and ligand-binding domains functioned like the TR-2 isoform on these promoters, confirming that the amino terminus of TR-2 was both necessary and sufficient to mediate this effect. By constructing deletion mutants of the TR-2 amino terminus, we demonstrate that amino acids 89-116 mediate this function. This domain, important in ligand-independent activation on negative TREs, is discrete from a previously described activation domain in the amino-terminal portion of TR-2. We conclude that the central nervous system-restricted TR-2 isoform has a unique effect on negative regulation by T₃ that can be mapped to amino acids 89-116 of the amino terminus of the human TR-2.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. V H Grommen, L. Arckens, T. Theuwissen, V. M Darras, and B. De Groef Thyroid hormone receptor {beta}2 is strongly up-regulated at all levels of the hypothalamo-pituitary-thyroidal axis during late embryogenesis in chicken J. Endocrinol., March 1, 2008; 196(3): 519 - 528. [Abstract] [Full Text] [PDF]

				M. Charbonneau, K. Harper, F. Grondin, M. Pelmus, P. P. McDonald, and C. M. Dubois Hypoxia-inducible Factor Mediates Hypoxic and Tumor Necrosis Factor {alpha}-induced Increases in Tumor Necrosis Factor-{alpha} Converting Enzyme/ADAM17 Expression by Synovial Cells J. Biol. Chem., November 16, 2007; 282(46): 33714 - 33724. [Abstract] [Full Text] [PDF]

				P. Guimont, F. Grondin, and C. M. Dubois Sox9-dependent transcriptional regulation of the proprotein convertase furin Am J Physiol Cell Physiol, July 1, 2007; 293(1): C172 - C183. [Abstract] [Full Text] [PDF]

				H. Tian, M. A. Mahajan, C. T. Wong, I. Habeos, and H. H. Samuels The N-Terminal A/B Domain of the Thyroid Hormone Receptor-{beta}2 Isoform Influences Ligand-Dependent Recruitment of Coactivators to the Ligand-Binding Domain Mol. Endocrinol., September 1, 2006; 20(9): 2036 - 2051. [Abstract] [Full Text] [PDF]

				S. McMahon, M. Charbonneau, S. Grandmont, D. E. Richard, and C. M. Dubois Transforming Growth Factor beta1 Induces Hypoxia-inducible Factor-1 Stabilization through Selective Inhibition of PHD2 Expression J. Biol. Chem., August 25, 2006; 281(34): 24171 - 24181. [Abstract] [Full Text] [PDF]

				J. M. Blumberg, I. Tzameli, I. Astapova, F. S. Lam, J. S. Flier, and A. N. Hollenberg Complex Role of the Vitamin D Receptor and Its Ligand in Adipogenesis in 3T3-L1 Cells J. Biol. Chem., April 21, 2006; 281(16): 11205 - 11213. [Abstract] [Full Text] [PDF]

				M.-B. Poirier, L. Laflamme, and M.-F. Langlois Identification and characterization of RanBPM, a novel coactivator of thyroid hormone receptors. J. Mol. Endocrinol., April 1, 2006; 36(2): 313 - 325. [Abstract] [Full Text] [PDF]

				P.-Q. Yuan and H. Yang Hypothyroidism increases Fos immunoreactivity in cholinergic neurons of brain medullary dorsal vagal complex in rats Am J Physiol Endocrinol Metab, November 1, 2005; 289(5): E892 - E899. [Abstract] [Full Text] [PDF]

				M.-B. Poirier, G. Hamann, M.-E. Domingue, M. Roy, T. Bardati, and M.-F. Langlois General Receptor for Phosphoinositides 1, a Novel Repressor of Thyroid Hormone Receptor Action that Prevents Deoxyribonucleic Acid Binding Mol. Endocrinol., August 1, 2005; 19(8): 1991 - 2005. [Abstract] [Full Text] [PDF]

				W. Wan, B. Farboud, and M. L. Privalsky Pituitary Resistance to Thyroid Hormone Syndrome Is Associated with T3 Receptor Mutants that Selectively Impair {beta}2 Isoform Function Mol. Endocrinol., June 1, 2005; 19(6): 1529 - 1542. [Abstract] [Full Text] [PDF]

				S.-W. Kim, S.-C. Ho, S.-J. Hong, K. M. Kim, E. C. So, M. Christoffolete, and J. W. Harney A Novel Mechanism of Thyroid Hormone-dependent Negative Regulation by Thyroid Hormone Receptor, Nuclear Receptor Corepressor (NCoR), and GAGA-binding Factor on the Rat CD44 Promoter J. Biol. Chem., April 15, 2005; 280(15): 14545 - 14555. [Abstract] [Full Text] [PDF]

				S. McMahon, F. Grondin, P. P. McDonald, D. E. Richard, and C. M. Dubois Hypoxia-enhanced Expression of the Proprotein Convertase Furin Is Mediated by Hypoxia-inducible Factor-1: IMPACT ON THE BIOACTIVATION OF PROPROTEINS J. Biol. Chem., February 25, 2005; 280(8): 6561 - 6569. [Abstract] [Full Text] [PDF]

				S. M. Dupre, H. Guissouma, F. Flamant, I. Seugnet, T. S. Scanlan, J. D. Baxter, J. Samarut, B. A. Demeneix, and N. Becker Both Thyroid Hormone Receptor (TR){beta}1 and TR{beta}2 Isoforms Contribute to the Regulation of Hypothalamic Thyrotropin-Releasing Hormone Endocrinology, May 1, 2004; 145(5): 2337 - 2345. [Abstract] [Full Text] [PDF]

				C. Liu, E. Goshu, A. Wells, and C.-M. Fan Identification of the Downstream Targets of SIM1 and ARNT2, a Pair of Transcription Factors Essential for Neuroendocrine Cell Differentiation J. Biol. Chem., November 7, 2003; 278(45): 44857 - 44867. [Abstract] [Full Text] [PDF]

				X. Meng, Y.-F. Yang, X. Cao, M. V. Govindan, M. Shuen, A. N. Hollenberg, J. S. Mymryk, and P. G. Walfish Cellular Context of Coregulator and Adaptor Proteins Regulates Human Adenovirus 5 Early Region 1A-Dependent Gene Activation by the Thyroid Hormone Receptor Mol. Endocrinol., June 1, 2003; 17(6): 1095 - 1105. [Abstract] [Full Text] [PDF]

				N. Shibusawa, A. N. Hollenberg, and F. E. Wondisford Thyroid Hormone Receptor DNA Binding Is Required for Both Positive and Negative Gene Regulation J. Biol. Chem., January 3, 2003; 278(2): 732 - 738. [Abstract] [Full Text] [PDF]

				M.-H. Laprise, F. Grondin, P. Cayer, P. P. McDonald, and C. M. Dubois Furin gene (fur) regulation in differentiating human megakaryoblastic Dami cells: involvement of the proximal GATA recognition motif in the P1 promoter and impact on the maturation of furin substrates Blood, November 15, 2002; 100(10): 3578 - 3587. [Abstract] [Full Text] [PDF]

				N. Vasudevan, S. Ogawa, and D. Pfaff Estrogen and Thyroid Hormone Receptor Interactions: Physiological Flexibility by Molecular Specificity Physiol Rev, October 1, 2002; 82(4): 923 - 944. [Abstract] [Full Text] [PDF]

				H. Guissouma, S. M. Dupre, N. Becker, E. Jeannin, I. Seugnet, B. Desvergne, and B. A. Demeneix Feedback on Hypothalamic TRH Transcription Is Dependent on Thyroid Hormone Receptor N Terminus Mol. Endocrinol., July 1, 2002; 16(7): 1652 - 1666. [Abstract] [Full Text] [PDF]

				J. D. Baxter, P. Goede, J. W. Apriletti, B. L. West, W. Feng, K. Mellstrom, R. J. Fletterick, R. L. Wagner, P. J. Kushner, R. C. J. Ribeiro, et al. Structure-Based Design and Synthesis of a Thyroid Hormone Receptor (TR) Antagonist Endocrinology, February 1, 2002; 143(2): 517 - 524. [Abstract] [Full Text] [PDF]

				N. Becker, I. Seugnet, H. Guissouma, S. M. Dupre, and B. A. Demeneix Nuclear Corepressor and Silencing Mediator of Retinoic and Thyroid Hormone Receptors Corepressor Expression Is Incompatible with T3-Dependent TRH Regulation Endocrinology, December 1, 2001; 142(12): 5321 - 5331. [Abstract] [Full Text] [PDF]

				S. Ando, N. J. Sarlis, E. H. Oldfield, and P. M. Yen Somatic Mutation of TR{beta} Can Cause a Defect in Negative Regulation of TSH in a TSH-Secreting Pituitary Tumor J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5572 - 5576. [Abstract] [Full Text] [PDF]

				K. Gauthier, M. Plateroti, C. B. Harvey, G. R. Williams, R. E. Weiss, S. Refetoff, J. F. Willott, V. Sundin, J.-P. Roux, L. Malaval, et al. Genetic Analysis Reveals Different Functions for the Products of the Thyroid Hormone Receptor {alpha} Locus Mol. Cell. Biol., July 15, 2001; 21(14): 4748 - 4760. [Abstract] [Full Text] [PDF]

				Z. Yang and M. L. Privalsky Isoform-Specific Transcriptional Regulation by Thyroid Hormone Receptors: Hormone-Independent Activation Operates through a Steroid Receptor Mode of Coactivator Interaction Mol. Endocrinol., July 1, 2001; 15(7): 1170 - 1185. [Abstract] [Full Text] [PDF]

				P. M. Yen Physiological and Molecular Basis of Thyroid Hormone Action Physiol Rev, July 1, 2001; 81(3): 1097 - 1142. [Abstract] [Full Text] [PDF]

				R. L. Wagner, B. R. Huber, A. K. Shiau, A. Kelly, S. T. Cunha Lima, T. S. Scanlan, J. W. Apriletti, J. D. Baxter, B. L. West, and R. J. Fletterick Hormone Selectivity in Thyroid Hormone Receptors Mol. Endocrinol., March 1, 2001; 15(3): 398 - 410. [Abstract] [Full Text]

				Q.-L. Li, E. Jansen, G. A. Brent, and T. C. Friedman Regulation of prohormone convertase 1 (PC1) by thyroid hormone Am J Physiol Endocrinol Metab, January 1, 2001; 280(1): E160 - E170. [Abstract] [Full Text] [PDF]

				G. R. Williams Cloning and Characterization of Two Novel Thyroid Hormone Receptor beta Isoforms Mol. Cell. Biol., November 15, 2000; 20(22): 8329 - 8342. [Abstract] [Full Text]

				Q.-L. Li, E. Jansen, G. A. Brent, S. Naqvi, J. F. Wilber, and T. C. Friedman Interactions between the Prohormone Convertase 2 Promoter and the Thyroid Hormone Receptor Endocrinology, September 1, 2000; 141(9): 3256 - 3266. [Abstract] [Full Text] [PDF]

				C. Oberste-Berghaus, K. Zanger, K. Hashimoto, R. N. Cohen, A. N. Hollenberg, and F. E. Wondisford Thyroid Hormone-independent Interaction between the Thyroid Hormone Receptor beta 2 Amino Terminus and Coactivators J. Biol. Chem., January 21, 2000; 275(3): 1787 - 1792. [Abstract] [Full Text] [PDF]

				Z. Yang, S.-H. Hong, and M. L. Privalsky Transcriptional Anti-repression. THYROID HORMONE RECEPTOR beta -2 RECRUITS SMRT COREPRESSOR BUT INTERFERES WITH SUBSEQUENT ASSEMBLY OF A FUNCTIONAL COREPRESSOR COMPLEX J. Biol. Chem., December 24, 1999; 274(52): 37131 - 37138. [Abstract] [Full Text] [PDF]

				K. W. Sloop, B. C. Meier, J. L. Bridwell, G. E. Parker, A. M. Schiller, and S. J. Rhodes Differential Activation of Pituitary Hormone Genes by Human Lhx3 Isoforms with Distinct DNA Binding Properties Mol. Endocrinol., December 1, 1999; 13(12): 2212 - 2225. [Abstract] [Full Text]

				H. Guissouma, M. T. Ghorbel, I. Seugnet, T. Ouatas, and B. A. Demeneix Physiological regulation of hypothalamic TRH transcription in vivo is T3 receptor isoform specific FASEB J, December 1, 1998; 12(15): 1755 - 1764. [Abstract] [Full Text]

				F. Blanchette, N. Rivard, P. Rudd, F. Grondin, L. Attisano, and C. M. Dubois Cross-talk between the p42/p44 MAP Kinase and Smad Pathways in Transforming Growth Factor beta 1-induced Furin Gene Transactivation J. Biol. Chem., August 31, 2001; 276(36): 33986 - 33994. [Abstract] [Full Text] [PDF]