Wsb1-KO Mouse

Wsb1, also known as WD repeat and suppressor of cytokine signaling box containing 1, is an E3 ubiquitin ligase. It functions as a substrate recognition protein within an E3 ubiquitin ligase complex, mediating ubiquitinylation and proteolytic degradation of diverse targets. It is involved in multiple pathways such as β -catenin signaling, NF -κB regulation, and is associated with processes like thyroid hormone homeostasis, immune regulation, glucose metabolism, and hypoxia [2]. It has significance in developmental biology and is dysregulated in several types of cancer, thus being potentially crucial for understanding tumorigenesis and cancer progression.

In cancer, Wsb1 has been found to form a feedforward circuit with c -Myc. Wsb1 is a direct target gene of c -Myc and positively regulates c -Myc expression through the β -catenin pathway, promoting cancer development [1]. In prostate cancer, increased Wsb1 expression is associated with higher grades and worse prognosis, and it has a central role in influencing other key genes like EZH1, EZH2, WNT10a, and WNT10b [3]. In lung fibrosis, conditional deletion of Wsb1 in adult mice ameliorated bleomycin-induced pulmonary fibrosis. Wsb1-deficient mice showed reduced lipofibroblast to myofibroblast transition but enhanced alveolar type 2 cell proliferation and differentiation into alveolar type 1 cells, suggesting Wsb1's role in myofibroblast accumulation and alveolar epithelial regeneration [4]. In myocardial ischemia-reperfusion injury, overexpression of Wsb1 relieved injury, as it activated β -catenin signaling by promoting GSK3β ubiquitination [5].

In conclusion, Wsb1 is an E3 ubiquitin ligase with diverse functions in various biological processes and disease conditions. Gene knockout and conditional knockout mouse models have been instrumental in revealing its roles in cancer progression, lung fibrosis, and myocardial ischemia-reperfusion injury, providing insights into potential therapeutic targets for these diseases.

References:

1. Gao, Xiaomeng, You, Jieqiong, Gong, Yanling, Yang, Bo, Cao, Ji. 2021. WSB1 regulates c-Myc expression through β-catenin signaling and forms a feedforward circuit. In Acta pharmaceutica Sinica. B, 12, 1225-1239. doi:10.1016/j.apsb.2021.10.021. https://pubmed.ncbi.nlm.nih.gov/35530152/

2. Haque, Moinul, Kendal, Joseph Keith, MacIsaac, Ryan Matthew, Demetrick, Douglas James. 2016. WSB1: from homeostasis to hypoxia. In Journal of biomedical science, 23, 61. doi:10.1186/s12929-016-0270-3. https://pubmed.ncbi.nlm.nih.gov/27542736/

3. Boldrini, Laura, Bardi, Massimo. 2023. WSB1 Involvement in Prostate Cancer Progression. In Genes, 14, . doi:10.3390/genes14081558. https://pubmed.ncbi.nlm.nih.gov/37628609/

4. Chong, Lei, Zou, Lihui, Xiang, Liyan, Zhang, Hailin, Zhang, Jin-San. 2024. WSB1, a Hypoxia-Inducible E3 Ligase, Promotes Myofibroblast Accumulation and Attenuates Alveolar Epithelial Regeneration in Mouse Lung Fibrosis. In The American journal of pathology, 194, 656-672. doi:10.1016/j.ajpath.2024.01.010. https://pubmed.ncbi.nlm.nih.gov/38325552/

5. Fang, Lini, Tao, Yang, Che, Guoying, Ren, Min, Liu, Yujie. 2024. WSB1, as an E3 ligase, restrains myocardial ischemia-reperfusion injury by activating β-catenin signaling via promoting GSK3β ubiquitination. In Molecular medicine (Cambridge, Mass.), 30, 31. doi:10.1186/s10020-024-00800-3. https://pubmed.ncbi.nlm.nih.gov/38395742/