CK2-Mediated Phosphorylation Upregulates the Stability of USP13 and Promotes Ovarian Cancer Cell Proliferation

Simple Summary Ubiquitin-specific Peptidase 13 (USP13) is highly amplified and promotes tumorigenesis and metastasis in ovarian cancer. However, post-translational modifications and their functions on USP13 are largely unknown. This study revealed that USP13 is phosphorylated at Thr122, which upregulates the stability of USP13 at a post-translation level. Notably, mutation of Thr122 diminished the effect of USP13 on the increased proliferation of ovarian cancer cells. Overall, we uncovered a new mechanism for the regulation of USP13 stability via a post-translational modification, suggesting novel therapeutics targeting USP13 in USP13-amplified cancers. Ubiquitin-specific Peptidase 13 (USP13) is a deubiquitinating enzyme that regulates the stability or function of its substrate. USP13 is highly amplified in human ovarian cancer, and elevated expression of USP13 promotes tumorigenesis and metastasis of ovarian cancer. However, there is little known about USP13 post-translational modifications and their role in ovarian cancer. Here, we found that USP13 is phosphorylated at Thr122 in ovarian cancer cells. Phosphorylated Thr122 (pT122) on endogenous USP13 was observed in most human ovarian cancer cells, and the abundance of this phosphorylation was correlated to the total level of USP13. We further demonstrated that Casein kinase 2 (CK2) directly interacts with and phosphorylates USP13 at Thr122, which promotes the stability of USP13 protein. Finally, we showed that Threonine 122 is important for cell proliferation of ovarian cancer cells. Our findings may reveal a novel regulatory mechanism for USP13, which may lead to novel therapeutic targeting of USP13 in ovarian cancer.