Ubiquitin C-Terminal Hydrolase L1 regulates autophagy by inhibiting autophagosome formation through its deubiquitinating enzyme activity

doi:10.1016/j.bbrc.2018.02.140

	Ubiquitin C-Terminal Hydrolase L1 regulates autophagy by inhibiting autophagosome formation through its deubiquitinating enzyme activity
	Yan, Cong1,2,3 ; Huo, Huanhuan1 ; Yang, Cuiwei1,2,3 ; Zhang, Tao1,2,3 ; Chu, Yuanyuan1 ; Liu, Yanfen1,2,3
	2018-03-04
发表期刊	BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (IF:2.5[JCR-2023],2.7[5-Year])
ISSN	0006-291X
卷号	497 期号:2 页码:726-733
发表状态	已发表
DOI	10.1016/j.bbrc.2018.02.140
摘要	Ubiquitination modification has been shown to play a key role in autophagy. Increasing studies reported the involvement of de-ubiquitinating enzymes (DUBS) in autophagy pathway. To systematically search how DUBs manipulate autophagy, we utilized a double fluorescence tagged LC3 stable HeLa cell line, and did a genome wide screen of 55 human DUBs which is about 60% coverage of the DUB family. We found a bunch of DUBs have impact on autophagy by either changing the LC3 puncta formation or the autophagy flux. One of them, Ubiquitin C-Terminal Hydrolase L1 (UCHL1) correlated to Parkinson's disease, strongly affects autophagy by inhibiting autophagosome formation. We found UCHL1 overexpression inhibits LC3 puncta formation and is dependent on its DUB activity. Knockdown of UCHL1 significantly promotes LC3 puncta formation. Further study revealed that UCHL1 may affect autophagy by interacting with LC3 but not other autophagy related proteins. Interestingly, a Parkinson's disease related mutant UCHL1 193 M defects its DUB activity and can no longer inhibit autophagosome formation. We further screened 22 commercially available DUB inhibitors and found two potent UCHL1 inhibitors LDN-57444 (LDN) and NSC632839 (NSC), when treating cells, both strongly induce LC3 puncta formation. Taken together, our results indicated a new insight into the manner in which DUB regulates autophagy and provided potential drugs for the Parkinson's disease. (C) 2018 Elsevier Inc. All rights reserved.
关键词	Ubiquitin C-Terminal Hydrolase L1 (UCHL1) Autophagy Autophagosome LC3 Parkinson's disease UCHL1 inhibitor
收录类别	SCI ; SCIE
语种	英语
资助项目	National Natural Science Foundation of China[31570781]
WOS研究方向	Biochemistry & Molecular Biology ; Biophysics
WOS类目	Biochemistry & Molecular Biology ; Biophysics
WOS记录号	WOS:000428229400039
出版者	ACADEMIC PRESS INC ELSEVIER SCIENCE
WOS关键词	MAMMALIAN AUTOPHAGY ; CELL-DEATH ; DISEASE ; UCH-L1 ; PROTEIN ; PATHOGENESIS ; MITOPHAGY ; PATHWAY ; SYSTEM ; CHAINS
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/20252
专题	生命科学与技术学院生命科学与技术学院_PI研究组_刘艳芬组生命科学与技术学院_硕士生生命科学与技术学院_博士生
通讯作者	Liu, Yanfen
作者单位	1.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
第一作者单位	生命科学与技术学院
通讯作者单位	生命科学与技术学院
第一作者的第一单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Yan, Cong,Huo, Huanhuan,Yang, Cuiwei,et al. Ubiquitin C-Terminal Hydrolase L1 regulates autophagy by inhibiting autophagosome formation through its deubiquitinating enzyme activity[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2018,497(2):726-733.
APA	Yan, Cong,Huo, Huanhuan,Yang, Cuiwei,Zhang, Tao,Chu, Yuanyuan,&Liu, Yanfen.(2018).Ubiquitin C-Terminal Hydrolase L1 regulates autophagy by inhibiting autophagosome formation through its deubiquitinating enzyme activity.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,497(2),726-733.
MLA	Yan, Cong,et al."Ubiquitin C-Terminal Hydrolase L1 regulates autophagy by inhibiting autophagosome formation through its deubiquitinating enzyme activity".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 497.2(2018):726-733.