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

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

doi:10.3724/abbs.2023155

Acta Biochimica et Biophysica Sinica (Aug 2023)

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

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

Affiliations

Fu Gongyu: ["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","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"]
Li Shi-Ting: ["Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China"]
Jiang Zetan: ["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","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"]
Mao Qiankun: ["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","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"]
Xiong Nanchi: ["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","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"]
Li Xiang: ["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"]
Hao Yijie: ["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","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"]
Zhang Huafeng: ["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","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"]

DOI: https://doi.org/10.3724/abbs.2023155
Journal volume & issue: Vol. 55
pp. 1370 – 1379

Abstract

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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.

Published in Acta Biochimica et Biophysica Sinica

ISSN: 1672-9145 (Print); 1745-7270 (Online)
Publisher: China Science Publishing & Media Ltd.
Country of publisher: China
LCC subjects: Science: Chemistry: Organic chemistry: Biochemistry; Science: Biology (General): Genetics
Website: https://www.sciengine.com/ABBS/home

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