机构：[1]State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Research Unit of Proteomics & Research and Development of New Drug of Chinese Academy of Medical Sciences, Beijing Institute of Lifeomics, 38 Science Park Road, Beijing 102206, China[2]School of Basic Medical Science, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery of Ministry of Education, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China[3]Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA[4]Guizhou University School of Medicine, Guiyang 550025, China[5]Second Clinical Medicine Collage, Guangzhou University Chinese Medicine, Guangzhou 510006, China
Ubiquitin chain specificity has been described for some deubiquitinases (DUBs) but lacks a comprehensive profiling in vivo. We used quantitative proteomics to compare the seven lysine-linked ubiquitin chains between wild-type yeast and its 20 DUB-deletion strains, which may reflect the linkage specificity of DUBs in vivo. Utilizing the specificity and ubiquitination heterogeneity, we developed a method termed DUB-mediated identification of linkage-specific ubiquitinated substrates (DILUS) to screen the ubiquitinated lysine residues on substrates modified with certain chains and regulated by specific DUB. Then we were able to identify 166 Ubp2-regulating substrates with 244 sites potentially modified with K63-linked chains. Among these substrates, we further demonstrated that cyclophilin A (Cpr1) modified with K63-linked chain on K151 site was regulated by Ubp2 and mediated the nuclear translocation of zinc finger protein Zpr1. The K48-linked chains at non-K151 sites of Cpr1 were mainly regulated by Ubp3 and served as canonical signals for proteasome-mediated degradation.
基金：
Chinese National Basic Research ProgramsNational Basic Research Program of China [2017YFA0505100, 2017YFA0505002, 2017YFC0906600, 2017YFC0906700]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31700723, 31670834, 31870824, 31901037, 91839302]; Innovation Foundation of Medicine [16CXZ027, AWS17J008, BWS17J032]; National Megaprojects for Key Infectious Diseases [2018ZX10302302]; Guangzhou Science and Technology Innovation & Development Project [201802020016]; Unilevel 21st Century Toxicity Program [MA-2018-02170N]; Foundation of State Key Lab of Proteomics [SKLP-K201704]; National Institutes of Health of United StatesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R37GM43601]
第一作者机构：[1]State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Research Unit of Proteomics & Research and Development of New Drug of Chinese Academy of Medical Sciences, Beijing Institute of Lifeomics, 38 Science Park Road, Beijing 102206, China
共同第一作者：
通讯作者：
通讯机构：[1]State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Research Unit of Proteomics & Research and Development of New Drug of Chinese Academy of Medical Sciences, Beijing Institute of Lifeomics, 38 Science Park Road, Beijing 102206, China[2]School of Basic Medical Science, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery of Ministry of Education, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China[4]Guizhou University School of Medicine, Guiyang 550025, China[5]Second Clinical Medicine Collage, Guangzhou University Chinese Medicine, Guangzhou 510006, China
推荐引用方式(GB/T 7714)：
Li Yanchang,Lan Qiuyan,Gao Yuan,et al.Ubiquitin Linkage Specificity of Deubiquitinases Determines Cyclophilin Nuclear Localization and Degradation[J].ISCIENCE.2020,23(4):doi:10.1016/j.isci.2020.100984.
APA：
Li, Yanchang,Lan, Qiuyan,Gao, Yuan,Xu, Cong,Xu, Zhongwei...&Xu, Ping.(2020).Ubiquitin Linkage Specificity of Deubiquitinases Determines Cyclophilin Nuclear Localization and Degradation.ISCIENCE,23,(4)
MLA：
Li, Yanchang,et al."Ubiquitin Linkage Specificity of Deubiquitinases Determines Cyclophilin Nuclear Localization and Degradation".ISCIENCE 23..4(2020)
