蛋白酶体翻译后修饰功能机制研究

Mechanistic Studies of Post-translational Modifications on the Proteasome

蛋白酶体是真核细胞内介导蛋白质特异性降解的主要复合物,在蛋白质质量控制和细胞稳态维持中发挥关键作用。研究发现,蛋白酶体含量或功能的异常会导致癌症、神经退行性疾病等诸多人类恶性疾病。围绕蛋白酶体的活性调控,已经发展了多种靶向药物,加强对蛋白酶体活性精确调控机制的研究具有重要的学术价值与临床意义。蛋白酶体的含量、组装及其活性的调节受多层次的精细调控,本文简要介绍了蛋白酶体的组成亚基、结构特征、转录调控与组装机制,着重阐述磷酸化、泛素化和乙酰化等翻译后修饰对蛋白酶体的调控机制及其生物学意义,以期为深入揭示蛋白酶体调控机制带来新启发。

The proteasome is the main complex for specific protein degradation in eukaryotic cells,which plays a key role in protein quality control and cell homeostasis maintenance.It is found that abnormal content or function of the proteasome can lead to many human serious diseases such as cancer and neurodegenerative disorders,and several targeted drugs have been developed for the regulation of proteasome activity.Therefore,it is of great academic value and clinical significance to strengthen the research on the precise regulation mechanism of proteasome activity.The content,assembly and activity of the proteasome are regulated rigorously by multiple levels.In this paper,we summarize the composition subunits,structural features,transcriptional regulation and assembly mechanism of proteasome,and focus on the mechanistic regulation and biological significance of post-translational modifications such as phosphorylation,ubiquitination and acetylation on proteasome,which might be helpful to reveal the regulation mechanism of proteasome in the near future.