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

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 physiol...

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Main Authors: Fu Gongyu, Li Shi-Ting, Jiang Zetan, Mao Qiankun, Xiong Nanchi, Li Xiang, Hao Yijie, Zhang Huafeng
Format: Article
Language:English
Published: China Science Publishing & Media Ltd. 2023-08-01
Series:Acta Biochimica et Biophysica Sinica
Subjects:
Online Access:https://www.sciengine.com/doi/10.3724/abbs.2023155
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author Fu Gongyu
Li Shi-Ting
Jiang Zetan
Mao Qiankun
Xiong Nanchi
Li Xiang
Hao Yijie
Zhang Huafeng
author_facet Fu Gongyu
Li Shi-Ting
Jiang Zetan
Mao Qiankun
Xiong Nanchi
Li Xiang
Hao Yijie
Zhang Huafeng
author_sort Fu Gongyu
collection DOAJ
description 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.
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spelling doaj.art-1d5f8f78ea80408ca35b6efb83d2f3e92023-11-06T08:30:38ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452023-08-01551370137910.3724/abbs.202315520d259ccPGAM5 deacetylation mediated by SIRT2 facilitates lipid metabolism and liver cancer proliferationFu Gongyu0Li Shi-Ting1Jiang Zetan2Mao Qiankun3Xiong Nanchi4Li Xiang5Hao Yijie6Zhang Huafeng7["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"]["Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China"]["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"]["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"]["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"]["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"]["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"]["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"]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.https://www.sciengine.com/doi/10.3724/abbs.2023155metabolic reprogramingPGAM5protein acetylationSIRT2ME1liver cancer
spellingShingle Fu Gongyu
Li Shi-Ting
Jiang Zetan
Mao Qiankun
Xiong Nanchi
Li Xiang
Hao Yijie
Zhang Huafeng
PGAM5 deacetylation mediated by SIRT2 facilitates lipid metabolism and liver cancer proliferation
Acta Biochimica et Biophysica Sinica
metabolic reprograming
PGAM5
protein acetylation
SIRT2
ME1
liver cancer
title PGAM5 deacetylation mediated by SIRT2 facilitates lipid metabolism and liver cancer proliferation
title_full PGAM5 deacetylation mediated by SIRT2 facilitates lipid metabolism and liver cancer proliferation
title_fullStr PGAM5 deacetylation mediated by SIRT2 facilitates lipid metabolism and liver cancer proliferation
title_full_unstemmed PGAM5 deacetylation mediated by SIRT2 facilitates lipid metabolism and liver cancer proliferation
title_short PGAM5 deacetylation mediated by SIRT2 facilitates lipid metabolism and liver cancer proliferation
title_sort pgam5 deacetylation mediated by sirt2 facilitates lipid metabolism and liver cancer proliferation
topic metabolic reprograming
PGAM5
protein acetylation
SIRT2
ME1
liver cancer
url https://www.sciengine.com/doi/10.3724/abbs.2023155
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