Usp2-KO Mouse

Usp2, short for ubiquitin-specific processing protease 2, is a multifunctional deubiquitinating enzyme. It plays a significant role in multiple biological processes by modulating the stability of various proteins. Usp2 is involved in pathways such as cell cycle regulation, carcinogenesis, and immune response [2]. It can deubiquitinate proteins like cyclins, Aurora-A, and epidermal growth factor, influencing cell cycle progression and tumorigenesis [2].

In cancer, loss-of-function studies have shown multiple effects. Depletion of Usp2 in colorectal and prostate cancer cells leads to endoplasmic reticulum-associated degradation of PD-L1, enhancing T-cell-mediated killing and antitumor immunity in mice, suggesting its role in tumor immune evasion [1]. In gastric cancer, inhibiting the Usp2-E2F4 axis suppresses autophagic machinery essential for zinc homeostasis, reducing cancer cell growth, invasion, and metastasis [3]. In addition, in lung cancer, Usp2 may suppress the disease by reducing ARID2 protein degradation via ubiquitination [4].

In conclusion, Usp2 is a key deubiquitinating enzyme involved in various biological functions, especially in cancer-related processes. Gene knockout or knockdown studies in cancer cell lines and mouse models have revealed its roles in tumor immune evasion, autophagy regulation, and cancer cell invasion and migration, providing potential therapeutic targets for cancer treatment [1,3,4].

References:

1. Kuang, Zean, Liu, Xiaojia, Zhang, Na, Song, Danqing, Deng, Hongbin. 2023. USP2 promotes tumor immune evasion via deubiquitination and stabilization of PD-L1. In Cell death and differentiation, 30, 2249-2264. doi:10.1038/s41418-023-01219-9. https://pubmed.ncbi.nlm.nih.gov/37670038/

2. Kitamura, Hiroshi, Hashimoto, Mayuko. 2021. USP2-Related Cellular Signaling and Consequent Pathophysiological Outcomes. In International journal of molecular sciences, 22, . doi:10.3390/ijms22031209. https://pubmed.ncbi.nlm.nih.gov/33530560/

3. Xiao, Wenjing, Wang, Jianqun, Wang, Xiaojing, Tong, Qiangsong, Zheng, Liduan. 2022. Therapeutic targeting of the USP2-E2F4 axis inhibits autophagic machinery essential for zinc homeostasis in cancer progression. In Autophagy, 18, 2615-2635. doi:10.1080/15548627.2022.2044651. https://pubmed.ncbi.nlm.nih.gov/35253629/

4. Zhu, Lihuan, Chen, Zhizhong, Guo, Tianxing, Guo, Lingwen, Pan, Xiaojie. 2022. USP2 Inhibits Lung Cancer Pathogenesis by Reducing ARID2 Protein Degradation via Ubiquitination. In BioMed research international, 2022, 1525216. doi:10.1155/2022/1525216. https://pubmed.ncbi.nlm.nih.gov/36567903/