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Phosphoproteomics Reveals the AMPK Substrate Network in Response to DNA Damage and Histone Acetylation

文献类型：期刊论文

作者Jiang, Yuejing1,3; Cong, Xiaoji2,3; Jiang, Shangwen2,3; Dong, Ying1,3; Zhao, Lei2; Zang, Yi1; Tan, Minjia2; Li, Jia1,4
刊名GENOMICS PROTEOMICS & BIOINFORMATICS
出版日期2022-08-01
卷号20期号:4页码:597-613
ISSN号1672-0229
关键词AMPK Phosphoproteomics Histone modification DNA damage Apoptosis
DOI10.1016/j.gpb.2020.09.003
通讯作者Zang, Yi(yzang@simm.ac.cn) ; Tan, Minjia(mjtan@simm.ac.cn) ; Li, Jia(jli@simm.ac.cn)
英文摘要AMP-activated protein kinase (AMPK) is a conserved energy sensor that plays roles in diverse biological processes via phosphorylating various substrates. Emerging studies have demonstrated the regulatory roles of AMPK in DNA repair, but the underlying mechanisms remain to be fully understood. Herein, using mass spectrometry-based proteomic technologies, we systematically investigate the regulatory network of AMPK in DNA damage response (DDR). Our system-wide phosphoproteome study uncovers a variety of newly-identified potential substrates involved in diverse biological processes, whereas our system-wide histone modification analysis reveals a link between AMPK and histone acetylation. Together with these findings, we discover that AMPK promotes apoptosis by phosphorylating apoptosis-stimulating of p53 protein 2 (ASPP2) in an irradiation (IR)-dependent manner and regulates histone acetylation by phosphorylating histone deacetylase 9 (HDAC9) in an IR-independent manner. Besides, we reveal that disrupting the histone acetylation by the bromodomain BRD4 inhibitor JQ-1 enhances the sensitivity of AMPKdeficient cells to IR. Therefore, our study has provided a resource to investigate the interplay between phosphorylation and histone acetylation underlying the regulatory network of AMPK, which could be beneficial to understand the exact role of AMPK in DDR.
WOS关键词ACTIVATED PROTEIN-KINASE ; TUMOR-SUPPRESSOR ; CANCER-CELLS ; RADIATION RESPONSE ; METFORMIN ; P53 ; BROMODOMAIN ; LKB1 ; APOPTOSIS ; BRD4
资助项目National Natural Science Foundation of China[81872888] ; National Natural Science Foundation of China[81821005] ; National Natural Science Foundation of China[81673489] ; National Natural Science Foundation of China[31871414] ; Special Project on Precision Medicine under the National Key RD Program[2017YFC0906600] ; Shanghai Science and Technology Development Funds, China[19JC1416300] ; Key New Drug Creation and Manufacturing Program of China[2018ZX09711002-004] ; Key New Drug Creation and Manufacturing Program of China[2018ZX09711002-007] ; KC Wong Education Foundation
WOS研究方向Genetics & Heredity
语种英语
出版者ELSEVIER
WOS记录号WOS:000911143200001
源URL[http://119.78.100.183/handle/2S10ELR8/303537]  
专题新药研究国家重点实验室
通讯作者Zang, Yi; Tan, Minjia; Li, Jia
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Chem Prote Ctr, Shanghai 201203, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
4.Pilot Natl Lab Marine Sci & Technol Qingdao, Open Studio Druggabil Res Marine Nat Prod, Qingdao 266237, Peoples R China
推荐引用方式
GB/T 7714		 Jiang, Yuejing,Cong, Xiaoji,Jiang, Shangwen,et al. Phosphoproteomics Reveals the AMPK Substrate Network in Response to DNA Damage and Histone Acetylation[J]. GENOMICS PROTEOMICS & BIOINFORMATICS,2022,20(4):597-613.
APA Jiang, Yuejing.,Cong, Xiaoji.,Jiang, Shangwen.,Dong, Ying.,Zhao, Lei.,...&Li, Jia.(2022).Phosphoproteomics Reveals the AMPK Substrate Network in Response to DNA Damage and Histone Acetylation.GENOMICS PROTEOMICS & BIOINFORMATICS,20(4),597-613.
MLA Jiang, Yuejing,et al."Phosphoproteomics Reveals the AMPK Substrate Network in Response to DNA Damage and Histone Acetylation".GENOMICS PROTEOMICS & BIOINFORMATICS 20.4(2022):597-613.

入库方式： OAI收割

来源：上海药物研究所

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