Regulation of PTEN and ovarian cancer progression by an E3 ubiquitin ligase RBCK1.

Ovarian cancer is one of the most lethal gynecologic malignancies worldwide, with the 5-year survival is less than 50%. Although some clinical achievements have been achieved, the overall survival rate has remained unchanged over the past 20 years. Therefore, it is necessary and urgent to develop the potential modifiers and therapeutic approach to improve the overall survival rate in ovarian cancer patients. RBCK1 is an RING protein E3 ubiquitin ligase, which was revealed to involve in the progression of several cancers through its ubiquitination function. In this research, we report that RBCK1 expression is significantly elevated in human ovarian cancer and strongly associated with poor patients' prognosis. RBCK1 deficiency induces cell apoptosis and inhibits cell proliferation and migration in ovarian cancer cells. In terms of molecular mechanism, we report that RBCK1 interacts with PTEN and promotes PTEN degradation in K48-linked ubiquitination. Our study suggests a new and interesting regulatory mechanism that RBCK1 facilitates PTEN degradation, which could be a new potential therapeutic target for ovarian cancer treatment.