Usp11-KO Mouse

USP11, a member of the ubiquitin-specific protease family, is a deubiquitinating enzyme (DUB) [6]. It is involved in multiple biological processes such as regulating cell cycle, DNA repair, signaling pathways, and tumor development [6]. By deubiquitinating target proteins, it affects their stability and function, thus participating in various cellular activities.

In spinal cord ischemia-reperfusion injury, knockout of USP11 (USP11-/Y) in mice decreased neuronal cell ferroptosis and promoted functional recovery, suggesting that USP11 may promote autophagy-dependent ferroptosis by stabilizing Beclin 1 [1]. In intervertebral disc degeneration, knockout of USP11 (USP11-/-) in vivo exacerbated the condition, while overexpression of USP11 ameliorated oxidative stress-induced ferroptosis by stabilizing Sirt3 [2]. In hepatocellular carcinoma, knockdown of USP11 inhibited the metastasis-promoting effect mediated by the USP11/eEF1A1/SP1/HGF axis [3]. In radiation-induced pneumonitis, Usp11-knockout (Usp11-/-) mice showed alleviated progression of the disease, with reduced pro-inflammatory cytokine expression and decreased pulmonary vessel permeability and immune cell infiltration [4]. In colorectal cancer, disruption of the USP11-mediated LSH deubiquitination increased cell sensitivity to ferroptosis [5]. In prostate cancer, USP11 knockdown significantly inhibited PCa cell growth [7].

In conclusion, USP11 plays crucial roles in multiple disease conditions, especially in regulating ferroptosis, tumor progression, and inflammatory responses. The use of USP11 knockout mouse models has revealed its function in these biological processes, providing potential therapeutic targets for treating spinal cord ischemia-reperfusion injury, intervertebral disc degeneration, hepatocellular carcinoma, radiation-induced pneumonitis, colorectal cancer, and prostate cancer.

References:

1. Rong, Yuluo, Fan, Jin, Ji, Chengyue, Cai, Weihua, Liu, Wei. 2021. USP11 regulates autophagy-dependent ferroptosis after spinal cord ischemia-reperfusion injury by deubiquitinating Beclin 1. In Cell death and differentiation, 29, 1164-1175. doi:10.1038/s41418-021-00907-8. https://pubmed.ncbi.nlm.nih.gov/34839355/

2. Zhu, Jian, Sun, Ruping, Sun, Kaiqiang, Kong, Fanqi, Shi, Jiangang. 2023. The deubiquitinase USP11 ameliorates intervertebral disc degeneration by regulating oxidative stress-induced ferroptosis via deubiquitinating and stabilizing Sirt3. In Redox biology, 62, 102707. doi:10.1016/j.redox.2023.102707. https://pubmed.ncbi.nlm.nih.gov/37099926/

3. Chen, Jin, Ning, Deng, Du, Pengcheng, Zhang, Bixiang, Chen, Xiaoping. 2023. USP11 potentiates HGF/AKT signaling and drives metastasis in hepatocellular carcinoma. In Oncogene, 43, 123-135. doi:10.1038/s41388-023-02847-8. https://pubmed.ncbi.nlm.nih.gov/37973952/

4. Tang, Yiting, Wang, Tingya, Gu, Liming, Cao, Jianping, Jiao, Yang. 2024. USP11 Exacerbates Radiation-Induced Pneumonitis by Activating Endothelial Cell Inflammatory Response via OTUD5-STING Signaling. In International journal of radiation oncology, biology, physics, 119, 1261-1274. doi:10.1016/j.ijrobp.2024.01.220. https://pubmed.ncbi.nlm.nih.gov/38364946/

5. Duan, Junyi, Huang, Daoyuan, Liu, Cheng, Wang, Weiping, Shao, Genze. 2023. USP11-mediated LSH deubiquitination inhibits ferroptosis in colorectal cancer through epigenetic activation of CYP24A1. In Cell death & disease, 14, 402. doi:10.1038/s41419-023-05915-9. https://pubmed.ncbi.nlm.nih.gov/37414755/

6. Guo, Tuanjie, Tang, Heting, Yuan, Zhihao, Zhang, Encheng, Wang, Xiang. 2022. The Dual Role of USP11 in Cancer. In Journal of oncology, 2022, 9963905. doi:10.1155/2022/9963905. https://pubmed.ncbi.nlm.nih.gov/35359344/

7. Pornour, Majid, Jeon, Hee-Young, Ryu, Hyunju, Barbieri, Christopher, Qi, Jianfei. 2024. USP11 promotes prostate cancer progression by up-regulating AR and c-Myc activity. In Proceedings of the National Academy of Sciences of the United States of America, 121, e2403331121. doi:10.1073/pnas.2403331121. https://pubmed.ncbi.nlm.nih.gov/39052835/