Ube2w, a type I ubiquitin-conjugating enzyme (E2), is involved in non-canonical ubiquitination processes, such as aminoacylated lysine ubiquitination and N-terminal ubiquitination of proteins [3,4]. It participates in multiple cellular pathways, including those related to immune response, DNA damage repair, and protein quality control [1,5,6]. Ube2w is of great biological importance as it impacts cell survival, proliferation, and apoptosis, thereby influencing various physiological and pathological states. Genetic models, like gene knockout (KO) mouse models, are valuable tools for studying Ube2w's functions.

In KO mouse models, Ube2w-knockdown mice in the DSS-induced colitis model showed increased weight loss, more severe diarrhea, and mucosal injuries, along with enhanced activation of the NF-κB signaling pathway and increased expression of pro-inflammatory mediators compared to control mice. In contrast, Ube2w overexpression ameliorated colitis severity by inhibiting pro-inflammatory mediator expression and NF-κB activation [1]. In another study, down-regulation of Ube2w in spermatogenic cells promoted cell apoptosis and was correlated with hypospermatogenesis [2].

In conclusion, Ube2w plays essential roles in maintaining normal physiological functions through its involvement in multiple pathways. The KO/CKO mouse models have revealed its significance in diseases like colitis and male infertility, providing insights into potential therapeutic strategies for these conditions [1,2].

References:

1. Wang, Shaoxin, Pu, Jiang, Li, Xiaowei, Luo, Zhe, Cui, Lihong. 2022. UBE2W Improves the Experimental Colitis by Inhibiting the NF-κB Signaling Pathway. In Digestive diseases and sciences, 67, 5529-5539. doi:10.1007/s10620-022-07453-4. https://pubmed.ncbi.nlm.nih.gov/35314916/

2. Lei, Bin, Xie, Lixia, Zhang, Shoubo, Shu, Fangpeng, Deng, Yushu. 2019. UBE2W down-regulation promotes cell apoptosis and correlates with hypospermatogenesis. In Andrologia, 52, e13474. doi:10.1111/and.13474. https://pubmed.ncbi.nlm.nih.gov/31710394/

3. Zang, Jia, Chen, Yulin, Liu, Chao, Yuan, Ying, Lin, Shixian. 2023. Genetic code expansion reveals aminoacylated lysine ubiquitination mediated by UBE2W. In Nature structural & molecular biology, 30, 62-71. doi:10.1038/s41594-022-00866-9. https://pubmed.ncbi.nlm.nih.gov/36593310/

4. Davies, Christopher W, Vidal, Simon E, Phu, Lilian, Kirkpatrick, Donald S, Koerber, James T. 2021. Antibody toolkit reveals N-terminally ubiquitinated substrates of UBE2W. In Nature communications, 12, 4608. doi:10.1038/s41467-021-24669-6. https://pubmed.ncbi.nlm.nih.gov/34326324/

5. Yuan, Yan, Xiao, Wei-Wei, Xie, Wei-Hao, Li, Rong-Zhen, Gao, Yuan-Hong. 2021. Prognostic value of ubiquitin E2 UBE2W and its correlation with tumor-infiltrating immune cells in breast cancer. In BMC cancer, 21, 479. doi:10.1186/s12885-021-08234-4. https://pubmed.ncbi.nlm.nih.gov/33931024/

6. Scaglione, K Matthew, Zavodszky, Eszter, Todi, Sokol V, Gestwicki, Jason E, Paulson, Henry L. . Ube2w and ataxin-3 coordinately regulate the ubiquitin ligase CHIP. In Molecular cell, 43, 599-612. doi:10.1016/j.molcel.2011.05.036. https://pubmed.ncbi.nlm.nih.gov/21855799/