Usp47, a deubiquitinase, is widely involved in multiple biological processes. It plays crucial roles in regulating various signaling pathways, such as Wnt-β-catenin signaling [2], and is associated with immune responses, cell metabolism, and tumor-related processes. Gene knockout (KO) or conditional knockout (CKO) mouse models are valuable for studying its functions.

In KO mouse models, Usp47 ablation compromises regulatory T cell (Treg) homeostasis and function in vivo, leading to inflammatory disorders, while boosting antitumor immune responses. It does so by inhibiting m6A-dependent c-Myc translation to maintain Treg metabolic and functional homeostasis [1]. In prostate cancer, Usp47 deficiency in mice slows tumor growth, reduces tumor burden, and enhances infiltration of immune cells, as well as altering T cell subsets in the tumor microenvironment [3]. Also, in myocardial infarction mouse models, inhibiting Usp47 alleviates cardiac functions, decreases infarct size, and reduces pro-inflammatory cytokines [4].

In conclusion, Usp47 is essential in maintaining Treg metabolic and functional homeostasis, modulating the tumor microenvironment, and influencing cardiac function and inflammatory immunity post-myocardial infarction. The use of KO/CKO mouse models has significantly contributed to understanding its role in these disease-related areas, providing potential therapeutic targets for cancer and autoimmune diseases, as well as insights into cardiac disease management.

References:

1. Wang, Aiting, Huang, Haiyan, Shi, Jian-Hong, Zhao, Ren, Zou, Qiang. 2023. USP47 inhibits m6A-dependent c-Myc translation to maintain regulatory T cell metabolic and functional homeostasis. In The Journal of clinical investigation, 133, . doi:10.1172/JCI169365. https://pubmed.ncbi.nlm.nih.gov/37788092/

2. Kassel, Sara, Hanson, Alison J, Benchabane, Hassina, Ahmed, Yashi, Lee, Ethan. 2023. USP47 deubiquitylates Groucho/TLE to promote Wnt-β-catenin signaling. In Science signaling, 16, eabn8372. doi:10.1126/scisignal.abn8372. https://pubmed.ncbi.nlm.nih.gov/36749823/

3. Wang, Qian-Lan, Lu, Shun-Yuan, Xu, Dan-Dan, Wang, Zhu-Gang, Zhang, Hong-Xin. 2024. USP47 deficiency in mice modulates tumor infiltrating immune cells and enhances antitumor immune responses in prostate cancer. In Cancer immunology, immunotherapy : CII, 73, 143. doi:10.1007/s00262-024-03730-5. https://pubmed.ncbi.nlm.nih.gov/38832955/

4. Wu, Zheng, Li, Wenzheng, Wang, Shaoping, Zheng, Ze. 2024. Role of deubiquitinase USP47 in cardiac function alleviation and anti-inflammatory immunity after myocardial infarction by regulating NLRP3 inflammasome-mediated pyroptotic signal pathways. In International immunopharmacology, 136, 112346. doi:10.1016/j.intimp.2024.112346. https://pubmed.ncbi.nlm.nih.gov/38850785/