Detection system for post-receptor disorders by three-dimensional imaging

三维成像受体后疾病检测系统

• 批准号: 14370330
• 负责人: TAKAYANAGI Ryoichi
• 金额: $ 8.96万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370330/
• 关键词: nuclear receptor; steroid receptor; cofactor; three-dimensional image; androgen; GFP; post-receptor; N-CoR

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.

本研究旨在构建一套利用高分辨率三维图像分析技术观察活体细胞中类固醇受体转录激活过程的系统，并利用该系统检测受体后的功能障碍，取得了以下成果。结果表明，核内受体和辅因子的亚核区分为3种类型。经典的类固醇受体如AR和GR形成细小的病灶，TR形成粗大的病灶，PPAR呈弥漫分布。研究发现，Runx2和Tob蛋白是类固醇受体的辅阻遏物。辅阻遏子N-cor可抑制AR的N-端和C-端之间的分子内相互作用，并抑制激动剂结合的AR的转录激活功能。核转位受损和核基质靶向被发现会导致雄激素不敏感综合征。这些结果表明，即使在常规和生化技术不能明确激素抵抗疾病的原因的情况下，高分辨率三维图像分析系统也是有用的。

项目成果

Glucocorticoid suppresses the canonicak Wnt signal in cultured human osteoblasts

糖皮质激素抑制培养的人成骨细胞中的 canonicak Wnt 信号

• 发表时间: 2005
• 期刊: Biochem Biophys Res Commun 329
• 作者: Ohnaka H et al.

高柳 涼一 他: "DHEA補充療法とその効果"治療学. 37. 1081-1084 (2003)

Ryoichi Takayanagi 等人：“DHEA 替代疗法及其效果”《Therapeutics》37. 1081-1084 (2003)。

大中 佳三 他: "スタチンとBMP"CLINICAL CALCIUM. 14. 287-288 (2004)

Yoshizo Onaka 等人：“他汀类药物和 BMP”《临床钙》14. 287-288 (2004)。

高柳 涼一: "核内ホルモン受容体異常症の原因とその病態"日本臨床. 60. 252-259 (2002)

Ryoichi Takayanagi：“核激素受体异常的原因和病理生理学”日本临床研究 60. 252-259 (2002)。

Activation Function-1 Domain of Androgen Receptor Contributes to the Interaction between Subnuclear Splicing Factor Compartment and Nuclear Receptor Compartment

• DOI: 10.1074/jbc.m203811200
• 发表时间: 2002-08
• 期刊: The Journal of Biological Chemistry
• 作者: Yue Zhao;K. Goto;M. Saitoh;T. Yanase;M. Nomura;T. Okabe;R. Takayanagi;H. Nawata