SIRT3‐dependent delactylation of cyclin E2 prevents hepatocellular carcinoma growth

-dependent deacetylase SIRT3, which can also catalyze removal of the lactyl moiety from lysine, is expressed at low levels in hepatocellular carcinoma (HCC) and has been suggested to be an HCC tumor suppressor. Here we report that SIRT3 can delactylate non-histone proteins and suppress HCC development. Using SILAC-based quantitative proteomics, we identify cyclin E2 (CCNE2) as one of the lactylated substrates of SIRT3 in HCC cells. Furthermore, our crystallographic study elucidates the mechanism of CCNE2 K348la delactylation by SIRT3. Our results further suggest that lactylated CCNE2 promotes HCC cell growth, while SIRT3 activation by Honokiol induces HCC cell apoptosis and prevents HCC outgrowth in vivo by…

• SS
  Salt Science Research Foundation
• NN
  National Natural Science Foundation of China

  Awards: 31972933, 21977121, 31770886, 82100230
• UO
  University of Science and Technology of China

  Award: KY9100000040
• NK
  National Key Research and Development Program of China

  Award: 2017YFA0505102
• FR
  Fundamental Research Funds for the Central Universities

  Award: WK9110000168
• FR
  Fundamental Research Funds for Central Universities of the Central South University

  Awards: WK9110000168, WK9100000009