Zhou Liang, Wang Hongfeng, Chen Dong, Gao Feng, Ying Zheng, Wang Guanghui
Laboratory of Molecular Neuropathology, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou 215021, China.
Int J Mol Sci. 2014 Aug 25;15(9):14997-5010. doi: 10.3390/ijms150914997.
The cellular protein quality control system in association with aggresome formation contributes to protecting cells against aggregation-prone protein-induced toxicity. p62/Sequestosome 1 (p62) is a multifunctional protein which plays an important role in protein degradation and aggregation. Although poly-ubiquitination is usually required for p62-mediated protein degradation and aggresome formation, several p62 substrates are processed to form aggregate in an ubiquitination-independent manner. In this study we demonstrate that p62 directly interacts with pathogenic Machado Joseph Disease (MJD)-associated protein ataxin-3 with polyglutamine (polyQ) expansion. Moreover, p62 could regulate the aggresome formation of pathogenic ataxin-3 and protect cells against pathogenic ataxin-3-induced cell death.
细胞蛋白质质量控制系统与聚集体的形成共同作用，有助于保护细胞免受易于聚集的蛋白质诱导的毒性。p62/聚集体装配蛋白1（p62）是一种多功能蛋白质，在蛋白质降解和聚集过程中发挥重要作用。虽然p62介导的蛋白质降解和聚集体形成通常需要多聚泛素化，但一些p62底物以不依赖泛素化的方式被加工形成聚集体。在本研究中，我们证明p62与致病性马查多-约瑟夫病（MJD）相关蛋白ataxin-3直接相互作用，ataxin-3存在多聚谷氨酰胺（polyQ）扩增。此外，p62可以调节致病性ataxin-3的聚集体形成，并保护细胞免受致病性ataxin-3诱导的细胞死亡。
