The elevated level of CCNB1 indicates more aggressive cancer and poor prognosis. However, the factors that cause CCNB1 upregulation remain enigmatic. Herein, we identify USP22 as a CCNB1 interactor and discover that both USP22 and CCNB1 are dramatically elevated with a strong positive correlation in colon cancer tissues. USP22 stabilizes CCNB1 by antagonizing proteasome-mediated degradation in a cell cycle-specific manner. Phosphorylation of USP22 by CDK1 enhances its activity in deubiquitinating CCNB1. The ubiquitin ligase anaphase-promoting complex (APC/C) targets USP22 for degradation by using the substrate adapter CDC20 during cell exit from M phase, presumably allowing CCNB1 degradation. Finally, we discover that USP22 knockdown leads to slower cell growth and reduced tumor size. Our study demonstrates that USP22 is a CCNB1 deubiquitinase, suggesting that targeting USP22 might be an effective approach to treat cancers with elevated CCNB1 expression.

中文翻译：

---

泛素特异性蛋白酶22是CCNB1的去泛素酶。

CCNB1水平升高表明更具侵略性的癌症和不良预后。但是，导致CCNB1上调的因素仍然是个谜。在本文中，我们将USP22鉴定为CCNB1相互作用子，并发现在结肠癌组织中USP22和CCNB1均显着升高，并具有很强的正相关性。USP22通过以细胞周期特异性方式拮抗蛋白酶体介导的降解来稳定CCNB1。CDK1对USP22的磷酸化增强了其在去泛素化CCNB1中的活性。泛素连接酶后期促进复合物（APC / C）通过在M期细胞退出过程中使用底物衔接子CDC20来靶向USP22降解，从而可能导致CCNB1降解。最后，我们发现USP22基因敲低导致细胞生长减慢和肿瘤大小减小。我们的研究表明，USP22是CCNB1去泛素酶，