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

作     者：Yuejing Jiang Xiaoji Cong Shangwen Jiang Ying Dong Lei Zhao Yi Zang Minjia Tan Jia Li Yuejing Jiang;Xiaoji Cong;Shangwen Jiang;Ying Dong;Lei Zhao;Yi Zang;Minjia Tan;Jia Li

作者机构：National Center for Drug ScreeningState Key Laboratory of Drug ResearchShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Chemical Proteomics CenterState Key Laboratory of Drug ResearchShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China University of Chinese Academy of SciencesBeijing 100049China Open Studio for Druggability Research of Marine Natural ProductsPilot National Laboratory for Marine Science and Technology(Qingdao)Qingdao 266237China 

出 版 物：《Genomics, Proteomics & Bioinformatics》 (基因组蛋白质组与生物信息学报（英文版）)

年 卷 期：2022年第20卷第4期

页      面：597-613页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 071007[理学-遗传学] 

基　　金：supported by the National Natural Science Foundation of China(Grant Nos.81872888,81821005,81673489,and 31871414) the Special Project on Precision Medicine under the National Key R&D Program(Grant No.2017YFC0906600) the Shanghai Science and Technology Development Funds,China(Grant No.19JC1416300) the Key New Drug Creation and Manufacturing Program of China(Grant Nos.2018ZX09711002-004 and 2018ZX09711002-007) the KC Wong Education Foundation 

主　　题：AMPK Phosphoproteomics Histone modification DNA damage Apoptosis 

摘      要：AMP-activated protein kinase(AMPK)is a conserved energy sensor that plays roles in diverse biological processes via phosphorylating various *** studies have demonstrated the regulatory roles of AMPK in DNA repair,but the underlying mechanisms remain to be fully ***,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 *** 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 ***,we reveal that disrupting the histone acetylation by the bromodomain BRD4 inhibitor JQ-1 enhances the sensitivity of AMPKdeficient cells to ***,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.