Functional analysis of proteasome activators

细胞内蛋白质的降解受泛素和蛋白酶体系统(UPS)的高度调控，UPS在细胞周期进程、应激反应、信号转导等许多生物学过程中发挥着关键作用。UPS的损伤与多种疾病有关，如神经退行性疾病和免疫疾病。蛋白酶体是一个桶形的多亚单位蛋白酶复合体，由潜在的20S核心颗粒(CP)和调节颗粒(RPS)组成。CP的功能受细胞内进化保守的多个RP调控。然而，每个RPS的功能和生理作用还没有被很好地理解。为了揭示每个RPS的特定功能，我们建立了一种蛋白酶体相关蛋白的敲除小鼠，该蛋白在哺乳动物中的功能尚未阐明。

Intracellular protein degradation is highly regulated by the Ubiquitin and Proteasome system (UPS), which plays critical roles in many biological processes such as cell cycle progression, stress response, signal transduction, and so on. The impairment of the UPS is associated with diverse array of diseases such as neurodegenerative diseases, and immune diseases.Proteasome is a barrel-shaped multisubunit protease complex that consists of latent 20S core particle (CP) and regulatory particles (RPs). The function of CP is regulated by evolutionarily conserved multiple RPs in the cells. However the function and physiological roles of each RPs are not well understood. To reveal the specific function of each RPs, we generated knockout mice of one of the proteasome-associated protein whose function has not yet been elucidated in mammal.