| Project/Area Number |
14370330
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Kyushu University |
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Principal Investigator |
TAKAYANAGI Ryoichi KYUSHU UNIVERSITY, Graduate School of Medical Sciences, Professor, 大学院・医学研究院, 教授 (30154917)
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| Co-Investigator(Kenkyū-buntansha) |
GOTO Kiminobu KYUSHU UNIVERSITY, Graduate School of Medical Sciences, Research Associate, 大学病院, 助手 (90284512)
OHNAKA Keizo KYUSHU UNIVERSITY, Graduate School of Medical Sciences, Assistant Professor, 大学院・医学研究院, 講師 (30325518)
KAWATE Hisaya KYUSHU UNIVERSITY, Graduate School of Medical Sciences, Research Associate, 大学院・医学研究院, 助手 (20336027)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥14,000,000 (Direct Cost: ¥14,000,000)
Fiscal Year 2004: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥7,200,000 (Direct Cost: ¥7,200,000)
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| Keywords | nuclear receptor / steroid receptor / cofactor / three-dimensional image / androgen / GFP / post-receptor / N-CoR |
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| Research Abstract |
This study was performed to construct the system which can observe transcription activation process of steroid receptors by high-resolution three-dimensional image analysis in living cells and to detect post-receptor disorders using that system, and the following results were obtained. It was revealed that subnuclear compartments for nuclear receptors and cofactors in the nucleus are divided into 3 types. The classical steroid receptors such as AR and GR form fine foci, TR forms coarse foci, and PPARs distribute diffusely. It was found that Runx2 and Tob protein are corepressors of steroid receptors. A corepressor, N-CoR inhibited the intramolecular interaction between the N- and C-terminal of AR, and suppressed transcription activation function after N-CoR was recruited to agonist-bound AR. Impaired nuclear translocation and nuclear matrix targeting were found to cause androgen insensitivity syndrome. These results demonstrated that the high-resolution three-dimensional image analysis system is useful even in the case that the conventional and biochemical techniques cannot clarify cause of steroid hormone resistance diseases.
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