PGAM5 deacetylation mediated by SIRT2 facilitates lipid metabolism and liver cancer proliferation  

作　　者：Gongyu Fu Shi-Ting Li Zetan Jiang Qiankun Mao Nanchi Xiong Xiang Li Yijie Hao Huafeng Zhang 

机构地区：[1]Anhui Key Laboratory of Hepatopancreatobiliary Surgery,Department of General Surgery,Anhui Provincial Hospital,the First Affiliated Hospital of USTC,Division of Life Science and Medicine,University of Science and Technology of China,Hefei 230027,China [2]Hefei National Laboratory for Physical Sciences at Microscale,the Chinese Academy of Sciences Key Laboratory of Innate Immunity and Chronic Disease,School of Basic Medical Sciences,Division of Life Science and Medicine,University of Science and Technology of China,Hefei 230027,China [3]Guangdong Cardiovascular Institute,Guangdong Provincial People’s Hospital,Guangdong Academy of Medical Sciences,Guangzhou 510080,China

出　　处：《Acta Biochimica et Biophysica Sinica》2023年第9期1370-1379,共10页生物化学与生物物理学报（英文版）

基　　金：supported by the grants from the National Natural Science Foundation of China(Nos.81930083,82192893,82103363,and 81821001);the Chinese Academy of Sciences(No.XDB39000000);the National Key R&D Program of China(No.2022YFA1304504);the Institute of Health and Medicine,Hefei Comprehensive National Science Center(No.DJK-LX-2022001);the Fundamental Research Funds for the Central Universities(No.YD2070002008);the China Postdoctoral Science Foundation(No.2021M700898).

摘　　要：Tumor metabolic reprogramming and epigenetic modification work together to promote tumorigenesis and development.Protein lysine acetylation,which affects a variety of biological functions of proteins,plays an important role under physiological and pathological conditions.Here,through immunoprecipitation and mass spectrum data,we show that phosphoglycerate mutase 5(PGAM5)deacetylation enhances malic enzyme 1(ME1)metabolic enzyme activity to promote lipid synthesis and proliferation of liver cancer cells.Mechanistically,we demonstrate that the deacetylase SIRT2 mediates PGAM5 deacetylation to activate ME1 activity,leading to ME1 dephosphorylation,subsequent lipid accumulation and the proliferation of liver cancer cells.Taken together,our study establishes an important role for the SIRT2-PGAM5-ME1 axis in the proliferation of liver cancer cells,suggesting a potential innovative cancer therapy.

关 键 词：metabolic reprograming PGAM5 protein acetylation SIRT2 ME1 liver cancer 

分 类 号：R73[医药卫生—肿瘤]