p62/Sequestosome 1 Regulates Aggresome Formation of Pathogenic Ataxin-3 with Expanded Polyglutamine

International Journal of Molecular Sciences

Liang Zhou¹  Hongfeng Wang¹  Dong Chen¹  Feng Gao¹  Zheng Ying¹ 

[1] 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; E-Mails:

关键词: ataxin-3;    polyglutamine;    p62;    aggregation;    aggresome;   

DOI  :  10.3390/ijms150914997

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.