Smurf2 enhances ubiquitin-mediated degradation of CASC3 and attenuates leukemia progression

Leukemia is a prevalent cancer worldwide with a poor prognosis, underscoring the need to understand the molecular mechanisms driving its development and progression. Smurf2 has been implicated in the development of numerous cancer types; however, its specific role in leukemia remains elusive. In this study, we investigated the function of Smurf2 in leukemia progression. Our findings demonstrate that upregulation of Smurf2 reduces viability of leukemia cells and induces apoptosis. Moreover, we identified CASC3 as a substrate of Smurf2 in leukemia. Smurf2 interacts with CASC3 and regulates its ubiquitination and degradation. Notably, Smurf2-mediated degradation of CASC3 depends on its 137-283 domain and lysine residue K254. Strikingly, the downregulation of Smurf2 promotes cell viability through CASC3, while overexpression of Smurf2 retards tumor growth in mouse models. Collectively, our results suggest that the Smurf2/CASC3 axis may serve as a potential therapeutic target for the treatment of leukemia.