SIRT3-dependent delactylation of cyclin E2 prevents hepatocellular carcinoma growth.

ABSTRACT: Lysine lactylation (Kla) is a recently discovered histone mark derived from metabolic lactate. The NAD⁺ -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 pr

SUBMITTER: Jin J 

PROVIDER: S-EPMC10157311 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature