Ube2s, the Ubiquitin Conjugating Enzyme E2 S, is a key member in the ubiquitination cascade, responsible for delivering ubiquitin to target proteins. Ubiquitination is involved in various cellular processes such as protein degradation, signal transduction, and cellular homeostasis [4,7].

In cancer research, Ube2s has been found to play oncogenic roles. In bladder cancer, it interacts with TRIM21 to mediate K11-linked ubiquitination of LPP, promoting lymphatic metastasis [1]. In hepatocellular carcinoma, it has multiple functions. It interacts with TRIM28 in the nucleus to ubiquitinate p27, accelerating the cell cycle [2]. It also promotes glycolysis by enhancing E3 enzyme-independent polyubiquitination of VHL [3]. In urinary bladder cancer, it ubiquitinates TSC1 to activate the mTORC1 pathway, promoting cancer progression [5]. In glioblastoma, it facilitates progression through the UBE2S/AKIP1-NF-κB axis [6]. In hepatocellular carcinoma, it promotes chemoresistance through the PTEN-AKT signaling pathway [7]. In mouse oocytes, loss-of-function experiments using Ube2s knockout mice showed that Ube2s is indispensable for mouse oocyte meiosis and female fertility, as its deletion causes meiosis I arrest [8].

In conclusion, Ube2s is crucial in multiple biological processes. Its functions in cancer progression and oocyte meiosis have been well-demonstrated through various functional studies including gene knockout models. These findings suggest Ube2s could be a potential therapeutic target in cancer treatment and provide insights into the mechanisms of female infertility [1,2,3,5,6,7,8].

References:

1. Xiao, Kanghua, Peng, Shengmeng, Lu, Junlin, Chen, Xu, Lin, Tianxin. 2023. UBE2S interacting with TRIM21 mediates the K11-linked ubiquitination of LPP to promote the lymphatic metastasis of bladder cancer. In Cell death & disease, 14, 408. doi:10.1038/s41419-023-05938-2. https://pubmed.ncbi.nlm.nih.gov/37422473/

2. Zhang, Ren-Yu, Liu, Ze-Kun, Wei, Ding, Chen, Zhi-Nan, Bian, Huijie. 2021. UBE2S interacting with TRIM28 in the nucleus accelerates cell cycle by ubiquitination of p27 to promote hepatocellular carcinoma development. In Signal transduction and targeted therapy, 6, 64. doi:10.1038/s41392-020-00432-z. https://pubmed.ncbi.nlm.nih.gov/33589597/

3. Zhang, Renyu, Li, Can, Zhang, Shuai, Chen, Zhinan, Bian, Huijie. 2024. UBE2S promotes glycolysis in hepatocellular carcinoma by enhancing E3 enzyme-independent polyubiquitination of VHL. In Clinical and molecular hepatology, 30, 771-792. doi:10.3350/cmh.2024.0236. https://pubmed.ncbi.nlm.nih.gov/38915206/

4. Zhang, Mengjun, Wang, Jialin, Zhang, Zidi, Lou, Xueling, Zhang, Lindong. 2024. Diverse roles of UBE2S in cancer and therapy resistance: Biological functions and mechanisms. In Heliyon, 10, e24465. doi:10.1016/j.heliyon.2024.e24465. https://pubmed.ncbi.nlm.nih.gov/38312603/

5. Tang, Hao, Fang, Tong, Ji, Meng, Zhang, Qiu-Yan, Wu, Jin-Sheng. 2021. UBE2S exerts oncogenic activities in urinary bladder cancer by ubiquitinating TSC1. In Biochemical and biophysical research communications, 578, 7-14. doi:10.1016/j.bbrc.2021.08.057. https://pubmed.ncbi.nlm.nih.gov/34520980/

6. Han, Zhibin, Xu, Lin, Wang, Aowen, Lin, Zhiguo, Hu, Li. 2024. UBE2S facilitates glioblastoma progression through activation of the NF-κB pathway via attenuating K11-linked ubiquitination of AKIP1. In International journal of biological macromolecules, 278, 134426. doi:10.1016/j.ijbiomac.2024.134426. https://pubmed.ncbi.nlm.nih.gov/39098687/

7. Gui, Liang, Zhang, Sicai, Xu, Yongzi, Zhu, Ying, Kong, Lianbao. 2021. UBE2S promotes cell chemoresistance through PTEN-AKT signaling in hepatocellular carcinoma. In Cell death discovery, 7, 357. doi:10.1038/s41420-021-00750-3. https://pubmed.ncbi.nlm.nih.gov/34785642/

8. Sun, Si-Min, Zhao, Bing-Wang, Li, Yuan-Yuan, Sun, Qing-Yuan, Wang, Zhen-Bo. 2024. Loss of UBE2S causes meiosis I arrest with normal spindle assembly checkpoint dynamics in mouse oocytes. In Development (Cambridge, England), 151, . doi:10.1242/dev.202285. https://pubmed.ncbi.nlm.nih.gov/38546043/