2. Academic Validation
  3. 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

  • Cancer Lett. 2021 Oct 10;518:266-277. doi: 10.1016/j.canlet.2021.07.044.
Tiantian Jing 1,  Boshi Wang 1,  Zhaojuan Yang 1,  Yun Liu 1,  Guiqin Xu 1,  Xiaoli Xu 2,  Kun Jiao 2,  Zehong Chen 1,  Lvzhu Xiang 1,  Li Zhang 3,  Yongzhong Liu 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200240, China.
  • 2 Shanghai Jiao Tong University School of Biomedical Engineering, Shanghai, 200030, China.
  • 3 State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200240, China. Electronic address: seekerzhangli@gmail.com.
  • 4 State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200240, China. Electronic address: liuyzg@shsci.org.
PMID: 34339800 DOI: 10.1016/j.canlet.2021.07.044
Abstract

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.

Keywords

DUSP1; E2F6; HCC; USP22.

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