Cloning and Characterization of Two Novel Thyroid Hormone Receptor beta  Isoforms

doi:10.1128/MCB.20.22.8329-8342.2000

This Article

	Full Text
	Full Text (PDF)
	Alert me when this article is cited
	Alert me if a correction is posted

Services

	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new issues of the journal
	Download to citation manager
	Reprints and Permissions
	Copyright Information
	Books from ASM Press
	MicrobeWorld

Citing Articles

	Citing Articles via HighWire
	Citing Articles via Google Scholar

Google Scholar

	Articles by Williams, G. R.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Williams, G. R.

Previous Article | Next Article

Molecular and Cellular Biology, November 2000, p. 8329-8342, Vol. 20, No. 22
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Cloning and Characterization of Two Novel Thyroid Hormone Receptor $beta$ Isoforms

Graham R. Williams^*

ICSM Molecular Endocrinology Group, Division of Medicine and MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London W12 ONN, United Kingdom

Received 25 April 2000/Returned for modification 8 June 2000/Accepted 21 August 2000

Thyroid hormone (T₃) activates nuclear receptor transcription factors, encoded by the TR $alpha$ (NR1A1) and TR $beta$ (NR1A2) genes, toregulate target gene expression. Several TR isoforms exist, andstudies of null mice have identified some unique functions forindividual TR variants, although considerable redundancy occurs,raising questions about the specificity of T₃ action. Thus, itis not known how diverse T₃ actions are regulated in target tissuesthat express multiple receptor variants. I have identified twonovel TR $beta$ isoforms that are expressed widely and result from alternativemRNA splicing. TR $beta$ 3 is a 44.6-kDa protein that contains an unique23-amino-acid N terminus and acts as a functional receptor. TR $Delta$ $beta$ 3is a 32.8-kDa protein that lacks a DNA binding domain but retainsligand binding activity and is a potent dominant-negative antagonist.The relative concentrations of $beta$ 3 and $Delta$ $beta$ 3 mRNAs vary between tissuesand with changes in thyroid status, indicating that alternativesplicing is tissue specific and T₃ regulated. These data providenovel insights into the mechanisms of T₃ action and define a newlevel of specificity that may regulate thyroid status intissue.

^* Mailing address: Molecular Endocrinology Group, MRC Clinical Sciences Centre, Hammersmith Hospital, Du Cane Rd., London W12ONN, United Kingdom. Phone: (44) 0208 383 1383. Fax: (44) 0208383 8306. E-mail: graham.williams{at}ic.ac.uk.

Molecular and Cellular Biology, November 2000, p. 8329-8342, Vol. 20, No. 22
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

This article has been cited by other articles:

Keijzer, R., Blommaart, P.-J. E, Labruyere, W. T, Vermeulen, J. L M, Doulabi, B. Z., Bakker, O., Tibboel, D., Lamers, W. H (2007). Expression of thyroid hormone receptors A and B in developing rat tissues; evidence for extensive posttranscriptional regulation. J Mol Endocrinol 38: 523-535 [Abstract] [Full Text]
Jones, I., Ng, L., Liu, H., Forrest, D. (2007). An Intron Control Region Differentially Regulates Expression of Thyroid Hormone Receptor {beta}2 in the Cochlea, Pituitary, and Cone Photoreceptors. Mol. Endocrinol. 21: 1108-1119 [Abstract] [Full Text]
Harvey, C. B., Bassett, J. H. D., Maruvada, P., Yen, P. M., Williams, G. R. (2007). The Rat Thyroid Hormone Receptor (TR) {Delta}{beta}3 Displays Cell-, TR Isoform-, and Thyroid Hormone Response Element-Specific Actions. Endocrinology 148: 1764-1773 [Abstract] [Full Text]
Flamant, F., Gauthier, K., Samarut, J. (2007). Thyroid Hormones Signaling Is Getting More Complex: STORMs Are Coming. Mol. Endocrinol. 21: 321-333 [Abstract] [Full Text]
Flamant, F., Baxter, J. D., Forrest, D., Refetoff, S., Samuels, H., Scanlan, T. S., Vennstrom, B., Samarut, J. (2006). International Union of Pharmacology. LIX. The Pharmacology and Classification of the Nuclear Receptor Superfamily: Thyroid Hormone Receptors. Pharmacol. Rev. 58: 705-711 [Full Text]
Hiroi, Y., Kim, H.-H., Ying, H., Furuya, F., Huang, Z., Simoncini, T., Noma, K., Ueki, K., Nguyen, N.-H., Scanlan, T. S., Moskowitz, M. A., Cheng, S.-Y., Liao, J. K. (2006). Rapid nongenomic actions of thyroid hormone. Proc. Natl. Acad. Sci. USA 103: 14104-14109 [Abstract] [Full Text]
Casas, F., Busson, M., Grandemange, S., Seyer, P., Carazo, A., Pessemesse, L., Wrutniak-Cabello, C., Cabello, G. (2006). Characterization of a Novel Thyroid Hormone Receptor {alpha} Variant Involved in the Regulation of Myoblast Differentiation. Mol. Endocrinol. 20: 749-763 [Abstract] [Full Text]
Conrad, A. H., Zhang, Y., Walker, A. R., Olberding, L. A., Hanzlick, A., Zimmer, A. J., Morffi, R., Conrad, G. W. (2006). Thyroxine Affects Expression of KSPG-Related Genes, the Carbonic Anhydrase II Gene, and KS Sulfation in the Embryonic Chicken Cornea. IOVS 47: 120-132 [Abstract] [Full Text]
Bassett, J. H. D., Swinhoe, R., Chassande, O., Samarut, J., Williams, G. R. (2006). Thyroid Hormone Regulates Heparan Sulfate Proteoglycan Expression in the Growth Plate. Endocrinology 147: 295-305 [Abstract] [Full Text]
Arnold, L. A., Estebanez-Perpina, E., Togashi, M., Jouravel, N., Shelat, A., McReynolds, A. C., Mar, E., Nguyen, P., Baxter, J. D., Fletterick, R. J., Webb, P., Guy, R. K. (2005). Discovery of Small Molecule Inhibitors of the Interaction of the Thyroid Hormone Receptor with Transcriptional Coregulators. J. Biol. Chem. 280: 43048-43055 [Abstract] [Full Text]
O'Shea, P. J., Bassett, J. H. D., Sriskantharajah, S., Ying, H., Cheng, S.-y., Williams, G. R. (2005). Contrasting Skeletal Phenotypes in Mice with an Identical Mutation Targeted to Thyroid Hormone Receptor {alpha}1 or {beta}. Mol. Endocrinol. 19: 3045-3059 [Abstract] [Full Text]
Barnard, J. C., Williams, A. J., Rabier, B., Chassande, O., Samarut, J., Cheng, S.-y., Bassett, J. H. D., Williams, G. R. (2005). Thyroid Hormones Regulate Fibroblast Growth Factor Receptor Signaling during Chondrogenesis. Endocrinology 146: 5568-5580 [Abstract] [Full Text]
Gloss, B., Giannocco, G., Swanson, E. A., Moriscot, A. S., Chiellini, G., Scanlan, T., Baxter, J. D., Dillmann, W. H. (2005). Different Configurations of Specific Thyroid Hormone Response Elements Mediate Opposite Effects of Thyroid Hormone and GC-1 on Gene Expression. Endocrinology 146: 4926-4933 [Abstract] [Full Text]
Boelaert, K, Franklyn, J A (2005). Thyroid hormone in health and disease. J Endocrinol 187: 1-15 [Abstract] [Full Text]
Ying, H., Furuya, F., Willingham, M. C., Xu, J., O'Malley, B. W., Cheng, S.-y. (2005). Dual Functions of the Steroid Hormone Receptor Coactivator 3 in Modulating Resistance to Thyroid Hormone. Mol. Cell. Biol. 25: 7687-7695 [Abstract] [Full Text]
Kahaly, G. J., Dillmann, W. H. (2005). Thyroid Hormone Action in the Heart. Endocr. Rev. 26: 704-728 [Abstract] [Full Text]
Prieur, X., Huby, T., Coste, H., Schaap, F. G., Chapman, M. J., Rodriguez, J. C. (2005). Thyroid Hormone Regulates the Hypotriglyceridemic Gene APOA5. J. Biol. Chem. 280: 27533-27543 [Abstract] [Full Text]
Vallejo, C. G., Seguido, A. M., Testillano, P. S., Risueno, M.-C. (2005). Thyroid hormone regulates tubulin expression in mammalian liver. Effects of deleting thyroid hormone receptor-{alpha} or -{beta}. Am. J. Physiol. Endocrinol. Metab. 289: E87-E94 [Abstract] [Full Text]
Mengeling, B. J., Pan, F., Privalsky, M. L. (2005). Novel Mode of Deoxyribonucleic Acid Recognition by Thyroid Hormone Receptors: Thyroid Hormone Receptor {beta}-Isoforms Can Bind as Trimers to Natural Response Elements Comprised of Reiterated Half-Sites. Mol. Endocrinol. 19: 35-51 [Abstract] [Full Text]
Esaki, T., Suzuki, H., Cook, M., Shimoji, K., Cheng, S.-Y., Sokoloff, L., Nunez, J. (2004). Cardiac glucose utilization in mice with mutated {alpha}- and {beta}-thyroid hormone receptors. Am. J. Physiol. Endocrinol. Metab. 287: E1149-E1153 [Abstract] [Full Text]
Frankton, S., Harvey, C. B., Gleason, L. M., Fadel, A., Williams, G. R. (2004). Multiple Messenger Ribonucleic Acid Variants Regulate Cell-Specific Expression of Human Thyroid Hormone Receptor {beta}1. Mol. Endocrinol. 18: 1631-1642 [Abstract] [Full Text]
Sheehan, T. E., Kumar, P. A., Hood, D. A. (2004). Tissue-specific regulation of cytochrome c oxidase subunit expression by thyroid hormone. Am. J. Physiol. Endocrinol. Metab. 286: E968-E974 [Abstract] [Full Text]
Dupre, S. M., Guissouma, H., Flamant, F., Seugnet, I., Scanlan, T. S., Baxter, J. D., Samarut, J., Demeneix, B. A., Becker, N. (2004). Both Thyroid Hormone Receptor (TR){beta}1 and TR{beta}2 Isoforms Contribute to the Regulation of Hypothalamic Thyrotropin-Releasing Hormone. Endocrinology 145: 2337-2345 [Abstract] [Full Text]
Manzano, J., Morte, B., Scanlan, T. S., Bernal, J. (2003). Differential Effects of Triiodothyronine and the Thyroid Hormone Receptor {beta}-Specific Agonist GC-1 on Thyroid Hormone Target Genes in the Brain. Endocrinology 144: 5480-5487 [Abstract] [Full Text]
Kamiya, Y., Zhang, X.-Y., Ying, H., Kato, Y., Willingham, M. C., Xu, J., O'Malley, B. W., Cheng, S.-Y. (2003). Modulation by Steroid Receptor Coactivator-1 of Target-Tissue Responsiveness in Resistance to Thyroid Hormone. Endocrinology 144: 4144-4153 [Abstract] [Full Text]
Suzuki, H., Cheng, S.-y. (2003). Compensatory Role of Thyroid Hormone Receptor (TR){alpha}1 in Resistance to Thyroid Hormone: Study in Mice with a Targeted Mutation in the TR{beta} Gene and Deficient in TR{alpha}1. Mol. Endocrinol. 17: 1647-1655 [Abstract] [Full Text]
O'Shea, P. J., Harvey, C. B., Suzuki, H., Kaneshige, M., Kaneshige, K., Cheng, S.-Y., Williams, G. R. (2003). A Thyrotoxic Skeletal Phenotype of Advanced Bone Formation in Mice with Resistance to Thyroid Hormone. Mol. Endocrinol. 17: 1410-1424 [Abstract] [Full Text]
Meng, X., Yang, Y.-F., Cao, X., Govindan, M. V., Shuen, M., Hollenberg, A. N., Mymryk, J. S., Walfish, P. G. (2003). Cellular Context of Coregulator and Adaptor Proteins Regulates Human Adenovirus 5 Early Region 1A-Dependent Gene Activation by the Thyroid Hormone Receptor. Mol. Endocrinol. 17: 1095-1105 [Abstract] [Full Text]
Suzuki, H., Zhang, X.-Y., Forrest, D., Willingham, M. C., Cheng, S.-Y. (2003). Marked Potentiation of the Dominant Negative Action of a Mutant Thyroid Hormone Receptor {beta} in Mice by the Ablation of One Wild-Type {beta} Allele. Mol. Endocrinol. 17: 895-907 [Abstract] [Full Text]
Nygard, M., Wahlstrom, G. M., Gustafsson, M. V., Tokumoto, Y. M., Bondesson, M. (2003). Hormone-Dependent Repression of the E2F-1 Gene by Thyroid Hormone Receptors. Mol. Endocrinol. 17: 79-92 [Abstract] [Full Text]
Moriyama, K., Tagami, T., Akamizu, T., Usui, T., Saijo, M., Kanamoto, N., Hataya, Y., Shimatsu, A., Kuzuya, H., Nakao, K. (2002). Thyroid Hormone Action Is Disrupted by Bisphenol A as an Antagonist. J. Clin. Endocrinol. Metab. 87: 5185-5190 [Abstract] [Full Text]
MALIK, R., HODGSON, H. (2002). The relationship between the thyroid gland and the liver. QJM 95: 559-569 [Abstract] [Full Text]
Zhang, X.-Y., Kaneshige, M., Kamiya, Y., Kaneshige, K., McPhie, P., Cheng, S.-Y. (2002). Differential Expression of Thyroid Hormone Receptor Isoforms Dictates the Dominant Negative Activity of Mutant {beta} Receptor. Mol. Endocrinol. 16: 2077-2092 [Abstract] [Full Text]
Gullberg, H., Rudling, M., Salto, C., Forrest, D., Angelin, B., Vennstrom, B. (2002). Requirement for Thyroid Hormone Receptor {beta} in T3 Regulation of Cholesterol Metabolism in Mice. Mol. Endocrinol. 16: 1767-1777 [Abstract] [Full Text]
Guissouma, H., Dupre, S. M., Becker, N., Jeannin, E., Seugnet, I., Desvergne, B., Demeneix, B. A. (2002). Feedback on Hypothalamic TRH Transcription Is Dependent on Thyroid Hormone Receptor N Terminus. Mol. Endocrinol. 16: 1652-1666 [Abstract] [Full Text]
Morte, B., Manzano, J., Scanlan, T., Vennstrom, B., Bernal, J. (2002). Deletion of the thyroid hormone receptor alpha 1 prevents the structural alterations of the cerebellum induced by hypothyroidism. Proc. Natl. Acad. Sci. USA 99: 3985-3989 [Abstract] [Full Text]
Flamant, F., Poguet, A.-L., Plateroti, M., Chassande, O., Gauthier, K., Streichenberger, N., Mansouri, A., Samarut, J. (2002). Congenital Hypothyroid Pax8-/- Mutant Mice Can Be Rescued by Inactivating the TR{alpha} Gene. Mol. Endocrinol. 16: 24-32 [Abstract] [Full Text]
Lin, H.-M., Kaneshige, M., Zhao, L., Zhang, X., Hanover, J. A., Cheng, S.-y. (2001). An Isoform of Branched-chain Aminotransferase Is a Novel Co-repressor for Thyroid Hormone Nuclear Receptors. J. Biol. Chem. 276: 48196-48205 [Abstract] [Full Text]
Mansen, A., Yu, F., Forrest, D., Larsson, L., Vennstrom, B. (2001). TRs Have Common and Isoform-Specific Functions in Regulation of the Cardiac Myosin Heavy Chain Genes. Mol. Endocrinol. 15: 2106-2114 [Abstract] [Full Text]
Becker, N., Seugnet, I., Guissouma, H., Dupre, S. M., Demeneix, B. A. (2001). Nuclear Corepressor and Silencing Mediator of Retinoic and Thyroid Hormone Receptors Corepressor Expression Is Incompatible with T3-Dependent TRH Regulation. Endocrinology 142: 5321-5331 [Abstract] [Full Text]
Itoh, Y., Esaki, T., Kaneshige, M., Suzuki, H., Cook, M., Sokoloff, L., Cheng, S.-Y., Nunez, J. (2001). Brain glucose utilization in mice with a targeted mutation in the thyroid hormone alpha or beta receptor gene. Proc. Natl. Acad. Sci. USA 10.1073/pnas.171319498v1 [Abstract] [Full Text]
Gauthier, K., Plateroti, M., Harvey, C. B., Williams, G. R., Weiss, R. E., Refetoff, S., Willott, J. F., Sundin, V., Roux, J.-P., Malaval, L., Hara, M., Samarut, J., Chassande, O. (2001). Genetic Analysis Reveals Different Functions for the Products of the Thyroid Hormone Receptor {alpha} Locus. Mol. Cell. Biol. 21: 4748-4760 [Abstract] [Full Text]
Itoh, Y., Esaki, T., Kaneshige, M., Suzuki, H., Cook, M., Sokoloff, L., Cheng, S.-Y., Nunez, J. (2001). Brain glucose utilization in mice with a targeted mutation in the thyroid hormone alpha or beta receptor gene. Proc. Natl. Acad. Sci. USA 98: 9913-9918 [Abstract] [Full Text]
Kinugawa, K., Yonekura, K., Ribeiro, R. C.J., Eto, Y., Aoyagi, T., Baxter, J. D., Camacho, S. A., Bristow, M. R., Long, C. S., Simpson, P. C. (2001). Regulation of Thyroid Hormone Receptor Isoforms in Physiological and Pathological Cardiac Hypertrophy. Circ. Res. 89: 591-598 [Abstract] [Full Text]

J. Bacteriol.	J. Virol.	Eukaryot. Cell

Microbiol. Mol. Biol. Rev.	Clin. Vaccine Immunol.	All ASM Journals

Cloning and Characterization of Two Novel Thyroid Hormone Receptor Isoforms

Cloning and Characterization of Two Novel Thyroid Hormone Receptor $beta$ Isoforms