한빛사 논문
Min Ji Yoon1,4, Boyoon Choi2,4, Eun Jin Kim1, Jiyeon Ohk2, Chansik Yang1, Yeon-Gil Choi1, Jinyoung Lee1, Chanhee Kang3, Hyun Kyu Song1, Yoon Ki Kim1, Jae-Sung Woo1, Yongcheol Cho1, Eui-Ju Choi1, Hosung Jung2,* & Chungho Kim1,*
1Department of Life Sciences, Korea University, Seoul, Republic of Korea.
2Department of Anatomy, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Republic of Korea.
3School of Biological Sciences, Seoul National University, Seoul, Republic of Korea.
4These authors contributed equally: Min Ji Yoon, Boyoon Choi.
*Corresponding author
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.
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