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 Miyamoto, T. Articles by Hashizume, K. Search for Related Content PubMed PubMed Citation Articles by Miyamoto, T. Articles by Hashizume, K. Social Bookmarking                      What's this?

Volume 272, Number 12, Issue of March 21, 1997 pp. 7752-7758
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

---

Inhibition of Peroxisome Proliferator Signaling Pathways by Thyroid Hormone Receptor
COMPETITIVE BINDING TO THE RESPONSE ELEMENT

(Received for publication, February 12, 1996, and in revised form, January 16, 1997)

From the Department of Geriatrics, Endocrinology and Metabolism, ^¶ Department of Biochemistry, Shinshu University School of Medicine, Matsumoto 390, Japan

Peroxisome proliferators (e.g. clofibric acid) and thyroid hormone play an important role in the metabolism of lipids. These effectors display their action through their own nuclear receptors, peroxisome proliferator-activated receptor (PPAR) and thyroid hormone receptor (TR). PPAR and TR are ligand-dependent, DNA binding, trans-acting transcriptional factors belonging to the erbA-related nuclear receptor superfamily. The present study focused on the convergence of the effectors on the peroxisome proliferator response element (PPRE). Transcriptional activation induced by PPAR through a PPRE was significantly suppressed by cotransfection of TR in transient transfection assays. The inhibition, however, was not affected by adding 3,5,3-triiodo-L-thyronine (T3). Furthermore, the inhibition was not observed in cells cotransfected with retinoic acid receptor or vitamin D3 receptor. The inhibitory action by TR was lost by introducing a mutation in the DNA binding domain of TR, indicating that competition for DNA binding is involved in the molecular basis of this functional interaction. Gel shift assays revealed that TRs, expressed in insect cells, specifically bound to the ³²P-labeled PPRE as heterodimers with the retinoid X receptor (RXR). Both PPAR and TR bind to PPRE, although only PPAR mediates transcriptional activation via PPRE. TR·RXR heterodimers are potential competitors with PPAR·RXR for binding to PPREs. It is concluded that PPAR-mediated gene expression is negatively controlled by TR at the level of PPAR binding to PPRE. We report here the novel action of thyroid hormone receptor in controlling gene expression through PPREs.

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

This article has been cited by other articles:

				K. Taketa, T. Matsumura, M. Yano, N. Ishii, T. Senokuchi, H. Motoshima, Y. Murata, S. Kim-Mitsuyama, T. Kawada, H. Itabe, et al. Oxidized Low Density Lipoprotein Activates Peroxisome Proliferator-activated Receptor-{alpha} (PPAR{alpha}) and PPAR{gamma} through MAPK-dependent COX-2 Expression in Macrophages J. Biol. Chem., April 11, 2008; 283(15): 9852 - 9862. [Abstract] [Full Text] [PDF]

				N. E. Buroker, M. E. Young, C. Wei, K. Serikawa, M. Ge, X.-H. Ning, and M. A. Portman The dominant negative thyroid hormone receptor beta-mutant {Delta}337T alters PPAR{alpha} signaling in heart Am J Physiol Endocrinol Metab, February 1, 2007; 292(2): E453 - E460. [Abstract] [Full Text] [PDF]

				O. M. Hyyti, X.-H. Ning, N. E. Buroker, M. Ge, and M. A. Portman Thyroid hormone controls myocardial substrate metabolism through nuclear receptor-mediated and rapid posttranscriptional mechanisms Am J Physiol Endocrinol Metab, February 1, 2006; 290(2): E372 - E379. [Abstract] [Full Text] [PDF]

				T. D. McClure, M. E. Young, H. Taegtmeyer, X.-H. Ning, N. E. Buroker, J. Lopez-Guisa, and M. A. Portman Thyroid hormone interacts with PPAR{alpha} and PGC-1 during mitochondrial maturation in sheep heart Am J Physiol Heart Circ Physiol, November 1, 2005; 289(5): H2258 - H2264. [Abstract] [Full Text] [PDF]

				S. Y. Honisett, L. Stojanovska, K. Sudhir, B. A. Kingwell, T. Dawood, and P. A. Komesaroff Hormone Therapy Impairs Endothelial Function in Postmenopausal Women with Type 2 Diabetes Mellitus Treated with Rosiglitazone J. Clin. Endocrinol. Metab., September 1, 2004; 89(9): 4615 - 4619. [Abstract] [Full Text] [PDF]

				C. D. Moyes Controlling muscle mitochondrial content J. Exp. Biol., December 15, 2003; 206(24): 4385 - 4391. [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. T. Miller, L. A. Scappino, S. M. Long, and J. C. Corton Role of Thyroid Hormones in Hepatic Effects of Peroxisome Proliferators Toxicol Pathol, January 1, 2001; 29(1): 149 - 155. [Abstract] [PDF]

				S. D Clarke, P. Thuillier, R. A Baillie, and X. Sha Peroxisome proliferator-activated receptors: a family of lipid-activated transcription factors Am. J. Clinical Nutrition, October 1, 1999; 70(4): 566 - 571. [Abstract] [Full Text] [PDF]

				T. Kakizawa, T. Miyamoto, K. Ichikawa, A. Kaneko, S. Suzuki, M. Hara, T. Nagasawa, T. Takeda, J.-i. Mori, M. Kumagai, et al. Functional Interaction between Oct-1 and Retinoid X Receptor J. Biol. Chem., July 2, 1999; 274(27): 19103 - 19108. [Abstract] [Full Text] [PDF]

				P. Gervois, S. Chopin-Delannoy, A. Fadel, G. Dubois, V. Kosykh, J.-C. Fruchart, J. Najïb, V. Laudet, and B. Staels Fibrates Increase Human REV-ERB{alpha} Expression in Liver via a Novel Peroxisome Proliferator-Activated Receptor Response Element Mol. Endocrinol., March 1, 1999; 13(3): 400 - 409. [Abstract] [Full Text]

				D. W. Singleton, X.-D. Lei, S. J. Webb, R. A. Prough, and T. E. Geoghegan Cytochrome P-450 mRNAs Are Modulated by Dehydroepiandrosterone, Nafenopin, and Triiodothyronine Drug Metab. Dispos., February 1, 1999; 27(2): 193 - 200. [Abstract] [Full Text]

				Y.-C. Zhou and D. J. Waxman Cross-talk between Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) and Peroxisome Proliferator-activated Receptor-alpha (PPARalpha ) Signaling Pathways. GROWTH HORMONE INHIBITION OF PPARalpha TRANSCRIPTIONAL ACTIVITY MEDIATED BY STAT5b J. Biol. Chem., January 29, 1999; 274(5): 2672 - 2681. [Abstract] [Full Text] [PDF]

				N. Vu-Dac, S. Chopin-Delannoy, P. Gervois, E. Bonnelye, G. Martin, J.-C. Fruchart, V. Laudet, and B. Staels The Nuclear Receptors Peroxisome Proliferator-activated Receptor alpha  and Rev-erbalpha Mediate the Species-specific Regulation of Apolipoprotein A-I Expression by Fibrates J. Biol. Chem., October 2, 1998; 273(40): 25713 - 25720. [Abstract] [Full Text] [PDF]