CK2-Mediated Phosphorylation Upregulates the Stability of USP13 and Promotes Ovarian Cancer Cell Proliferation.
CK2-Mediated Phosphorylation Upregulates the Stability of USP13 and Promotes Ovarian Cancer Cell Proliferation.
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泛素特异性肽酶13（USP 13）在卵巢癌中高度扩增并促进肿瘤发生和转移。然而，USP13上的翻译后修饰及其功能在很大程度上是未知的。这项研究表明，USP13在Thr122处被磷酸化，这在翻译后水平上调了USP13的稳定性。值得注意的是，Thr122突变减弱了USP 13对卵巢癌细胞增殖增加的影响。总的来说，我们发现了一种通过翻译后修饰调节USP13稳定性的新机制，这表明在USP13扩增的癌症中靶向USP13的新疗法。泛素特异性肽酶13（USP 13）是一种去泛素化酶，调节其底物的稳定性或功能。USP 13在人类卵巢癌中高度扩增，USP 13的表达升高促进卵巢癌的肿瘤发生和转移。然而，关于USP13的翻译后修饰及其在卵巢癌中的作用知之甚少。在这里，我们发现USP13在卵巢癌细胞中的Thr122处磷酸化。在大多数人卵巢癌细胞中观察到内源性USP 13上的磷酸化Thr122（pT122），并且这种磷酸化的丰度与USP 13的总水平相关。我们进一步证明，酪蛋白激酶2（CK2）直接与USP13相互作用并在Thr122磷酸化USP13，这促进了USP13蛋白的稳定性。最后，我们发现ThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThreeThre我们的研究结果可能揭示了USP13的一种新的调节机制，这可能导致USP13在卵巢癌中的新的治疗靶点。
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.
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