Ubiquitin Linkage Specificity of Deubiquitinases Determines Cyclophilin Nuclear Localization and Degradation
| Autor: | Lei Chang, Qiuyan Lan, Junzhu Wu, Ping Xu, Zhongwei Xu, Cong Xu, Yanchang Li, Yihao Wang, Daniel Finley, Zixin Deng, Fuchu He, Yuan Gao |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Zinc finger Multidisciplinary biology Chemistry Lysine Quantitative proteomics Omics 02 engineering and technology 021001 nanoscience & nanotechnology Article Yeast 3. Good health Cell biology 03 medical and health sciences Cyclophilin A 030104 developmental biology Ubiquitin biology.protein lcsh:Q 0210 nano-technology lcsh:Science Molecular Biology Cyclophilin Nuclear localization sequence |
| Zdroj: | iScience, Vol 23, Iss 4, Pp-(2020) iScience |
| ISSN: | 2589-0042 |
| Popis: | Summary 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. Graphical Abstract Highlights • Quantitative proteomics is used to reflect DUB's linkage specificity in vivo • DILUS is developed to decode the ubiquitin code on the level of ubiquitinated sites • K63 chains on K151 of Cpr1 regulated by Ubp2/Ubp3 mediates Zpr1's nuclear transition • K48 chains on non-K151 of Cpr1 regulated by Ubp3 controls its proteasomal proteolysis Molecular Biology; Omics |
| Databáze: | OpenAIRE |
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