2006 Fiscal Year Final Research Report Summary
Identification and characterization of a novel human thyroid hormone receptor isoform
| Project/Area Number |
17590973
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | National Hospital Organization, Kyoto Medical Center, Clinical Research Institute |
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Principal Investigator |
TAGAMI Tetsuya Kyoto Medical Center, Clinical Research Institute, Department of Endocrinology, Head of Laboratory, 内分泌研究部・分子内分泌研究室, 室長 (60273439)
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| Co-Investigator(Kenkyū-buntansha) |
MORIYAMA Kenji Kyoto Medical Center, Clinical Research Institute, Department of Endocrinology, Investigator, 内分泌研究部, 研究員 (00301739)
NARUSE Mitsuhide Kyoto Medical Center, Clinical Research Institute, Department of Endocrinology, Head of Department, 内分泌研究部, 部長 (40120018)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Thyroid hormone / Nuclear Receptor / Thyroid Hormone Receptor / Cloning / Transcription Factor |
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| Research Abstract |
Thyroid hormone exerts a pleiotropic effect on development and homeostasis. A novel thyroid hormone receptor β isoform (hereafter referred to as TRβ4) was cloned using PCR from a human pituitary cDNA library as a template. Analysis of the PCR products revealed a 137-bp insertion, which contains a stop codon in the middle, between the 5^<th> and 6^<th> exons that encode the ligand-binding domain of TRβ. The corresponding sequence of this insertion exists within the 5^<th> intron of the human TRβ gene and consensus splice sequences were found at the junction sites. RACE analysis revealed that TRβ4 is a carboxyl-terminal splicing variant of TRβ1. RT-PCR and. Northern blot analyses indicate that TRβ4 mRNA is expressed in various human tissues, and especially abundant in skeletal muscle. The TRβ4 protein was unable to bind thyroid hormone (T3) and transient transfection assays demonstrate that TRβ4 construct does not mediate regulation of either positively or negatively regulated reporter genes. Furthermore, TRβ4 interacts minimally with RXR and co-repressor proteins. TRβ4 inhibited transcription mediated by functional TRs when co-transfected with TRβ1, TRβ2 or TRα1. This dominant negative activity of TRβ4 was comparable to TRα2, but not as potent as mutant TRs that are found in the patients with resistance to thyroid hormone (RTH). Thus, this novel isoform may modulate T3 action as an endogenous antagonist in the tissue or cellular context.
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Research Products
(10 results)
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[Journal Article] Anti-thyroid Drugs Inhibit Thyroid Hormone Receptor-mediated Transcription.2007
Author(s)
Moriyama K, Tagami T, Usui T, Naruse M, Nambu T, Hataya Y, Kanamoto N, Li Y, Yasoda A, Arai H, Nakao K
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Journal Title
J Clin Endocrinol Metab 92・3
Pages: 1066-1072
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Anti-thyroid Drugs Inhibit Thyroid Hormone Receptor-mediated Transcription.2007
Author(s)
Moriyama K, Tagami T, Usui T, Naruse M, Nambu T, Hataya Y, Kanamoto N, Li Y, Yasoda A, Arai H, Nakao K.
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Journal Title
J Clin Endocrinol Metab 92(3)
Pages: 1066-1072
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Anti-thyroidal drugs, PTU and MMI, an alternative action on the transcriptional activity mediated by the thyroid hormone receptors.2005
Author(s)
Moriyama K, Tagami T, Usui T, Naruse M, Hataya Y, Kanamoto N, Li Y, Arai H, Akamizu T, Nakao K
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Journal Title
The 7th international workshop on thyroid hormone resistance Syllabus
Pages: 53
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Anti-thyroidal drugs, PTU and MMI, an alternative action on the transcriptional activity mediated by the thyroid hormone receptors.2005
Author(s)
Moriyama K, Tagami T, Usui T, Naruse M, Hataya Y, Kanamoto N, Li Y, Arai H, Akamizu T, Nakao K
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Journal Title
The 7th international workshop on thyroid hormone resistance. Syllabus
Pages: 53
Description
「研究成果報告書概要(欧文)」より
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