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Global identification of phospho-dependent SCF substrates reveals a FBXO22 phosphodegron and an ERK-FBXO22-BAG3 axis in tumorigenesis

文献类型：期刊论文

作者Liu, Ping1; Cong, Xiaoji1,2; Liao, Shengjie3; Jia, Xinglong1; Wang, Xiaomin2,4; Dai, Wei5; Zhai, Linhui1; Zhao, Lei1; Ji, Jing6; Ni, Duan
刊名CELL DEATH AND DIFFERENTIATION
出版日期2021-07-02
页码13
ISSN号1350-9047
DOI10.1038/s41418-021-00827-7
通讯作者Liu, Bin(liubin@jou.edu.cn) ; Tan, Minjia(mjtan@simm.ac.cn)
英文摘要SKP1-CUL1-F-box (SCF) ubiquitin ligases play fundamental roles in cellular functions. Typically, substrate phosphorylation is required for SCF recognition and subsequent degradation. However, phospho-dependent substrates remain largely unidentified. Here, using quantitative phoshoproteome approach, we performed a system-wide investigation of phospho-dependent SCF substrates. This strategy identified diverse phospho-dependent candidates. Biochemical verification revealed a mechanism by which SCFFBXO22 recognizes the motif XXPpSPXPXX as a conserved phosphodegron to target substrates for destruction. We further demonstrated BAG3, a HSP70 co-chaperone, is a bona fide substrate of SCFFBXO22. FBXO22 mediates BAG3 ubiquitination and degradation that requires ERK-dependent BAG3 phosphorylation at S377. FBXO22 depletion or expression of a stable BAG3 S377A mutant promotes tumor growth via defects in apoptosis and cell cycle progression in vitro and in vivo. In conclusion, our study identified broad phosphorylation-dependent SCF substrates and demonstrated a phosphodegron recognized by FBXO22 and a novel ERK-FBXO22-BAG3 axis involved in tumorigenesis.
WOS关键词PROTEIN-DEGRADATION ; PROTEOMICS REVEALS ; UBIQUITIN LIGASES ; ENRICHMENT ; RECOGNITION ; INHIBITOR ; SELECTION ; BAG3
资助项目Natural Science Foundation of China[32071432] ; Natural Science Foundation of China[81872888] ; Natural Science Foundation of China[81821005] ; Natural Science Foundation of China[91753203] ; Natural Science Foundation of China[81773018] ; Natural Science Foundation of China[71473074] ; National Key R&D Program of China[2020YFE020220] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program[2018ZX09711002-004] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12050406] ; Shanghai Science and Technology Committee[19JC1416300] ; Innovative Research Team of High-Level Local Universities in Shanghai[SSMUZDCX20181202] ; K. C. Wong Education Foundation
WOS研究方向Biochemistry & Molecular Biology ; Cell Biology
语种英语
出版者SPRINGERNATURE
WOS记录号WOS:000669170200001
源URL[http://119.78.100.183/handle/2S10ELR8/296792]  
专题新药研究国家重点实验室
通讯作者Liu, Bin; Tan, Minjia
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Chem Prote Ctr, State Key Lab Drug Res, Shanghai, Peoples R China
2.Univ Chinese Acad Sci, Beijing, Peoples R China
3.Hubei Polytech Univ, Hubei Key Lab Kidney Dis Pathogenesis & Intervent, Sch Med, Huangshi, Hubei, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai, Peoples R China
5.Hubei Polytech Univ, Sch Econ & Management, Ctr Informat Technol, Huangshi, Hubei, Peoples R China
6.Jiangsu Ocean Univ, Coll Pharm, Jiangsu Key Lab Marine Pharmaceut Compound Screen, Lianyungang, Peoples R China
7.Shanghai Jiao Tong Univ, Renji Hosp, State Key Lab Oncogenes & Related Genes, Sch Med, Shanghai, Peoples R China
8.Zhengzhou Univ, Sch Pharmaceut Sci, Zhengzhou, Peoples R China
推荐引用方式
GB/T 7714		 Liu, Ping,Cong, Xiaoji,Liao, Shengjie,et al. Global identification of phospho-dependent SCF substrates reveals a FBXO22 phosphodegron and an ERK-FBXO22-BAG3 axis in tumorigenesis[J]. CELL DEATH AND DIFFERENTIATION,2021:13.
APA Liu, Ping.,Cong, Xiaoji.,Liao, Shengjie.,Jia, Xinglong.,Wang, Xiaomin.,...&Tan, Minjia.(2021).Global identification of phospho-dependent SCF substrates reveals a FBXO22 phosphodegron and an ERK-FBXO22-BAG3 axis in tumorigenesis.CELL DEATH AND DIFFERENTIATION,13.
MLA Liu, Ping,et al."Global identification of phospho-dependent SCF substrates reveals a FBXO22 phosphodegron and an ERK-FBXO22-BAG3 axis in tumorigenesis".CELL DEATH AND DIFFERENTIATION (2021):13.

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来源：上海药物研究所

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