title: 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.
authors.affiliation: 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. zl123@mail.ustc.edu.cn.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhou
authors.affiliation: 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. wanghongfeng@suda.edu.cn.
authors.forename: Hongfeng
authors.initials: H
authors.lastname: Wang
authors.affiliation: 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. chendong@suda.edu.cn.
authors.forename: Dong
authors.initials: D
authors.lastname: Chen
authors.affiliation: 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. fgao@suda.edu.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.affiliation: 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. zheng.ying@suda.edu.cn.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Ying
authors.affiliation: 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. wanggh@suda.edu.cn.
authors.forename: Guanghui
authors.initials: G
authors.lastname: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000067699:Ataxin-3; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D066329:Protein Aggregates; D066263:Protein Aggregation, Pathological; D011485:Protein Binding; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism*; D000071456:Sequestosome-1 Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010455:Peptides; D066329:Protein Aggregates; D012097:Repressor Proteins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; C097188:polyglutamine; C092341:ATXN3 protein, human; D000067699:Ataxin-3