SUMOylation is essential for Sirt2 tumor-suppressor function in neuroblastoma

SUMOylation is an important post-translational modification that participates in a variety of cellular physiological and pathological processes in eukaryotic cells. Sirt2, a NAD(+)-dependent deacetylase, usually exerts a tumor-suppressor function. However, the role of SUMOylation in cancer cells is not fully known. In this study, we found that SUMOylation can occur in the Sirt2 protein at both lysine 183 and lysine 340 sites. SUMOylation did not affect Sirt2 localization or stability but was involved in P38-mTORC2-AKT cellular signal transduction via direct deacetylation on a new substrate MAPK/P38. SUMOylation-deficient Sirt2 lost the capability of suppressing tumor processes and showed resistance to the Sirt2-specific inhibitor AK-7 in neuroblastoma cells. Here, we revealed the important function of Sirt2-SUMOylation, which is closely associated with cellular signal transduction and is essential for suppressing tumorigenesis in neuroblastoma.