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

Abstract: 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.