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UXT chaperone prevents proteotoxicity by acting as an autophagy adaptor for p62-dependent aggrephagy

Authors
 Min Ji Yoon  ;  Boyoon Choi  ;  Eun Jin Kim  ;  Jiyeon Ohk  ;  Chansik Yang  ;  Yeon-Gil Choi  ;  Jinyoung Lee  ;  Chanhee Kang  ;  Hyun Kyu Song  ;  Yoon Ki Kim  ;  Jae-Sung Woo  ;  Yongcheol Cho  ;  Eui-Ju Choi  ;  Hosung Jung  ;  Chungho Kim 
Citation
 NATURE COMMUNICATIONS, Vol.12(1) : 1955, 2021-03 
Journal Title
 NATURE COMMUNICATIONS 
Issue Date
2021-03
MeSH
Animals ; Autophagy / drug effects ; Autophagy / genetics* ; Cell Cycle Proteins / genetics* ; Cell Cycle Proteins / metabolism ; Ganglia, Spinal / cytology ; Ganglia, Spinal / metabolism ; Gene Expression Regulation ; Genes, Reporter ; Green Fluorescent Proteins / genetics ; Green Fluorescent Proteins / metabolism ; HEK293 Cells ; HeLa Cells ; Humans ; Leupeptins / pharmacology ; Luminescent Proteins / genetics ; Luminescent Proteins / metabolism ; Molecular Chaperones / genetics* ; Molecular Chaperones / metabolism ; Motor Neurons / cytology ; Motor Neurons / drug effects ; Motor Neurons / metabolism ; Primary Cell Culture ; Proteasome Endopeptidase Complex / drug effects ; Proteasome Endopeptidase Complex / metabolism ; Protein Aggregates* / drug effects ; Protein Folding / drug effects ; Sequestosome-1 Protein / genetics* ; Sequestosome-1 Protein / metabolism ; Signal Transduction ; Superoxide Dismutase-1 / genetics* ; Superoxide Dismutase-1 / metabolism ; Transgenes ; Xenopus laevis
Abstract
p62/SQSTM1 is known to act as a key mediator in the selective autophagy of protein aggregates, or aggrephagy, by steering ubiquitinated protein aggregates towards the autophagy pathway. Here, we use a yeast two-hybrid screen to identify the prefoldin-like chaperone UXT as an interacting protein of p62. We show that UXT can bind to protein aggregates as well as the LB domain of p62, and, possibly by forming an oligomer, increase p62 clustering for its efficient targeting to protein aggregates, thereby promoting the formation of the p62 body and clearance of its cargo via autophagy. We also find that ectopic expression of human UXT delays SOD1(A4V)-induced degeneration of motor neurons in a Xenopus model system, and that specific disruption of the interaction between UXT and p62 suppresses UXT-mediated protection. Together, these results indicate that UXT functions as an autophagy adaptor of p62-dependent aggrephagy. Furthermore, our study illustrates a cooperative relationship between molecular chaperones and the aggrephagy machinery that efficiently removes misfolded protein aggregates.
Files in This Item:
T202101286.pdf Download
DOI
10.1038/s41467-021-22252-7
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
Yonsei Authors
Jung, Ho Sung(정호성) ORCID logo https://orcid.org/0000-0002-5059-8050
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/182451
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