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

Acta Biochim Biophys Sin (Shanghai). 2023 Aug 15;55(9):1370-1379. doi: 10.3724/abbs.2023155.

Abstract

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.

Keywords: ME1; PGAM5; SIRT2; liver cancer; metabolic reprograming; protein acetylation.

MeSH terms

  • Acetylation
  • Cell Proliferation
  • Humans
  • Lipid Metabolism
  • Lipids
  • Liver Neoplasms*
  • Mitochondrial Proteins / metabolism
  • Phosphoglycerate Mutase / genetics
  • Phosphoglycerate Mutase / metabolism
  • Phosphoprotein Phosphatases / metabolism
  • Sirtuin 2* / genetics
  • Sirtuin 2* / metabolism

Substances

  • Sirtuin 2
  • Phosphoglycerate Mutase
  • Lipids
  • SIRT2 protein, human
  • PGAM5 protein, human
  • Phosphoprotein Phosphatases
  • Mitochondrial Proteins

Grants and funding

This work was 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), and the China Postdoctoral Science Foundation (No. 2021M700898).