Ubiquitin Linkage Specificity of Deubiquitinases Determines Cyclophilin Nuclear Localization and Degradation

被引：19

作者：

Li, Yanchang ^{[1
]}

Lan, Qiuyan ^{[2
]}

Gao, Yuan ^{[1
]}

Xu, Cong ^{[1
]}

Xu, Zhongwei ^{[1
]}

Wang, Yihao ^{[1
]}

Chang, Lei ^{[1
]}

Wu, Junzhu ^{[2
]}

Deng, Zixin ^{[2
]}

He, Fuchu ^{[1
]}

Finley, Daniel ^{[3
]}

Xu, Ping ^{[1
,2
,4
,5
]}

机构：

[1] Chinese Acad Med Sci, Beijing Inst Life, State Key Lab Prote,Res Unit Prote & Res & Dev Ne, Beijing Proteome Res Ctr,Natl Ctr Prot Sci Beijin, 38 Sci Pk Rd, Beijing 102206, Peoples R China

[2] Wuhan Univ, Sch Basic Med Sci, Sch Pharmaceut Sci, Key Lab Combinatorial Biosynth & Drug Discovery,M, Wuhan 430071, Peoples R China

[3] Harvard Med Sch, Dept Cell Biol, Boston, MA 02115 USA

[4] Guizhou Univ, Sch Med, Guiyang 550025, Peoples R China

[5] Guangzhou Univ Chinese Med, Clin Med Collage 2, Guangzhou 510006, Peoples R China

来源：

ISCIENCE | 2020年 / 23卷 / 04期

基金：

美国国家卫生研究院; 中国国家自然科学基金;

关键词：

E3; LIGASE; GLOBAL ANALYSIS; POLYUBIQUITIN; PROTEOMICS; IDENTIFICATION; YEAST; QUANTIFICATION; PURIFICATION; UBIQUITYLATION; RECOGNITION;

D O I：

10.1016/j.isci.2020.100984

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：37

共 31 条

[31] Nuclear proteasomal degradation of Saccharomyces cerevisiae inorganic pyrophosphatase Ipp1p, a nucleocytoplasmic protein whose stability depends on its subcellular localization
Serrano-Bueno, Gloria
Manuel Madronal, Juan
Manzano-Lopez, Javier
Muniz, Manuel
Roman Perez-Castineira, Jose
Hernandez, Agustin
Serrano, Aurelio
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2019, 1866 (06): : 1019 - 1033

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