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

本研究通过高分辨率三维图像分析构建活细胞中类固醇受体转录激活过程的观察系统，并利用该系统检测受体后紊乱，得到如下结果：结果表明，核内核受体和辅因子的亚核室可分为3种类型。经典类固醇受体如AR、GR形成细灶，TR形成粗灶，ppar呈弥漫性分布。发现Runx2和Tob蛋白是类固醇受体的辅抑制因子。作为一种辅助抑制因子，N- cor抑制AR的N端和c端分子内相互作用，并在N- cor被募集到激动剂结合的AR后抑制转录激活功能。发现核易位受损和核基质靶向可导致雄激素不敏感综合征。这些结果表明，高分辨率三维图像分析系统是有用的，即使在情况下，传统和生化技术不能明确的类固醇激素抗性疾病的原因。

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.