Deubiquitination of the repressor E2F6 by USP22 facilitates AKT activation and tumor growth in hepatocellular carcinoma
Deubiquitination of the repressor E2F6 by USP22 facilitates AKT activation and tumor growth in hepatocellular carcinoma
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USP22 对阻遏蛋白 E2F6 的去泛素化促进了肝细胞癌中 AKT 的激活和肿瘤生长
DOI：
10.1016/j.canlet.2021.07.044
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发表时间：
2021-07-31
期刊：
影响因子：
9.7
通讯作者：
Liu, Yongzhong
中科院分区：
文献类型：
--
作者：
Jing, Tiantian;Wang, Boshi;Liu, Yongzhong
肿瘤相关蛋白的泛素化失调在肿瘤的发生和发展中起着至关重要的作用。去泛素化酶USP 22在某些类型的癌症中异常表达，并有助于侵袭性肿瘤进展。然而，USP 22在肝细胞癌（HCC）中促肿瘤发生功能的确切机制仍不清楚。在这里，我们报告说，E2 F6，口袋蛋白独立的转录抑制因子，是必不可少的肝癌细胞生长，其活动是由USP 22介导的去泛素化。USP 22与E2 F6相互作用并稳定E2 F6，导致磷酸酶DUSP 1的转录抑制。此外，涉及E2 F6抑制DUSP 1的过程增强了HCC细胞中的AKT活化。因此，这些发现为USP 22介导的致癌AKT信号传导控制提供了机制见解，强调了USP 22-E2 F6调控在HCC发展中的重要性。
Dysregulated ubiquitination of tumor-related proteins plays a critical role in tumor development and progression. The deubiquitinase USP22 is aberrantly expressed in certain types of cancer and contributes to aggressive tumor progression. However, the precise mechanism underlying the pro-tumorigenic function of USP22 in hepatocellular carcinoma (HCC) remains unclear. Here, we report that E2F6, a pocket protein-independent transcription repressor, is essential for HCC cell growth, and that its activities are controlled by USP22-mediated deubiquitination. USP22 interacts with and stabilizes E2F6, resulting in the transcriptional repression of phosphatase DUSP1. Moreover, the process involving DUSP1 repression by E2F6 strengthens AKT activation in HCC cells. Therefore, these findings provide mechanistic insights into the USP22-mediated control of oncogenic AKT signaling, emphasizing the importance of USP22-E2F6 regulation in HCC development.