摘要：SummaryUbiquitin specific protease 39 (USP39), an ortholog of Sad1p in yeast, is essential for spliceosome assembly during pre-mRNA splicing in human. Although it is known that USP39 is upregulated and plays an oncogenic role in hepatocellular carcinoma (HCC), the underlying mechanism remains unknown. The results of this study demonstrated that USP39 can be acetylated by the histone acetyltransferase MYST1, which is required for its proteasome-mediated degradation by Von Hippel-Lindau protein. In HCC cells, USP39 interacts with and is deacetylated by the lysine deacetylase sirtuin 7 (SIRT7). Notably, the deacetylation of USP39 by SIRT7 promotes its stability and thereby accelerates HCC cell proliferation and tumorigenesisin vitroandin vivo. Our data demonstrated a novel mechanism by which SIRT7 modulates the deacetylation of USP39 to promote HCC development, thus providing an effective anti-tumor therapeutic strategy for HCC.Graphical AbstractDisplay OmittedHighlights•SIRT7 modulates the deacetylation of USP39•MYST1 promotes the acetyl binding of USP39•USP39 acetylation induces its instabilityMolecular Biology; Cell Biology; Cancer
