In-depth Analysis of Proteasome-Mediated Regulatory Proteolysis

在过去的25年里，我们的研究工作集中在全面阐明蛋白酶体的结构和分子/生理功能，蛋白酶体是一个2.5-丙二醛复杂的多亚单位蛋白酶复合体。在这个项目中，我们研究了时空动力学和作用机制，如核转位和泛素受体的鉴定，通过鉴定为多个蛋白酶体专属伴侣而深入的蛋白酶体组装机制，以及新发现的胸腺蛋白酶体控制胸腺中CD8+T细胞的阳性选择的免疫学作用。此外，我们不仅进行了泛素研究，即通过PINK1/Parkin途径对线粒体进行质量控制，而且还进行了自噬研究，涉及到一个新的Nrf2依赖的压力调节系统，通过自噬选择性底物p62。

Over the past 25 years, our research work focused on elucidating comprehensively the structure and molecular/physiological functions of the proteasome, a 2.5-MDa sophisticated multisubunit protease complex. During this program, we have studied spatio-temporal dynamics and action mechanisms such as nuclear translocation and identification of ubiquitin receptors, in-depth mechanisms underling proteasome assembly by identifying as multiple proteasome-dedicated chaperones, and the immunological roles of the newly-discovered thymoproteasome that govern positive selection of CD8+ T cells in the thymus. In addition, we also conducted not only ubiquitin study; i.e., quality-control of mitochondria by the PINK1/Parkin pathway, but also autophagy study involving a novel Nrf2-dependent stress-regulated system by p62, an autophagy selective substrate.