USP39-mediated deubiquitination of Cyclin B1 promotes tumor cell proliferation and glioma progression

Background: The elevated Cyclin B1 expression contributes to various tumorigenesis and poor prognosis. Cyclin B1 expression could be regulated by ubiquitination and deubiquitination. However, the mechanism of how Cyclin B1 is deubiquitinated and its roles in human glioma remain unclear. Methods: Co-immunoprecipitation and other assays were performed to detect the interacting of Cyclin B1 and USP39. A series of in vitro and in vivo experiments were performed to investigate the effect of USP39 on the tumorigenicity of tumor cells. Results: USP39 interacts with Cyclin B1 and stabilizes its expression by deubiquitinating Cyclin B1. Notably, USP39 cleaves the K29-linked polyubiquitin chain on Cyclin B1 at Lys242. Additionally, overexpression of Cyclin B1 rescues the arrested cell cycle at G2/M transition and the suppressed proliferation of glioma cells caused by USP39 knockdown in vitro. Furthermore, USP39 promotes the growth of glioma xenograft in subcutaneous and in situ of nude mice. Finally, in human tumor specimens, the expression levels of USP39 and Cyclin B1 are positively relevant. Conclusion: Our data support the evidence that USP39 acts a novel deubiquitinating enzyme of Cyclin B1 and promoted tumor cell proliferation at least in part through Cyclin B1 stabilization, represents a promising therapeutic strategy for tumor patients.

Automated summary

The research finds that USP39 interacts with Cyclin B1 and stabilizes its expression by deubiquitinating Cyclin B1. The overexpression of USP39 promotes the proliferation of human glioma cells and is positively correlated with the expression levels of Cyclin B1. The study suggests that USP39 is a novel deubiquitinating enzyme of Cyclin B1 and promotes tumor cell proliferation through Cyclin B1 stabilization.