Usp31-KO Mouse

Usp31, also known as Ubiquitin-specific protease 31, is a member of the deubiquitinase family. It is involved in multiple important biological pathways, such as the NF-κB activation pathway [1,2,3]. Deubiquitinases like Usp31 play crucial roles in regulating protein stability and cellular signaling, which are fundamental for normal cell function and development. Genetic models, like gene knockout mouse models, are valuable tools for studying its functions.

In ApoE-/-mouse models, knockdown of macrophage-expressed circARCN1 led to decreased macrophage accumulation and inflammation in atherosclerotic plaques, which was associated with attenuated USP31-mediated NF-κB activation, suggesting that USP31 may be involved in the development of atherosclerosis [1]. In cervical cancer cells, site-specific mutagenesis of USP31 at Lys1264 increased its ubiquitin hydrolase activity, decreased p65 expression, and affected cancer cell growth and apoptosis, indicating the role of USP31 acetylation in tumorigenesis [2]. In rodent brain, USP48 (formerly USP31) acts as a nuclear deubiquitinase that induces synapse removal, interacts with NF-κB, and up-regulates NF-κB target genes to inhibit synaptogenesis [3]. In gastric cancer, USP31 binds to β-catenin, reduces its ubiquitination, activates the Wnt/β-catenin pathway and glycolysis, promoting cancer cell proliferation, invasion, and migration [4]. In lung squamous cell carcinoma, knockdown of USP31 reduced cell viability and blocked autophagy, while USP31 was shown to stabilize E2F1 expression through the proteasome pathway, promoting cancer cell growth and autophagy [5]. In non-alcoholic steatohepatitis mouse models, USP31 was involved in the SHH-HSP90β axis, where SHH reduced HSP90β ubiquitylation through USP31, promoting hepatic lipid synthesis and NASH development [6].

In conclusion, USP31 plays essential roles in various biological processes and disease conditions. Through model-based research, it has been shown to be involved in diseases such as atherosclerosis, cervical cancer, synapse remodeling-related disorders, gastric cancer, lung squamous cell carcinoma, and non-alcoholic steatohepatitis. These findings enhance our understanding of the biological functions of USP31 and its potential as a therapeutic target for these diseases.

References:

1. Pan, Zhicheng, Lv, Jialan, Zhao, Liding, Xu, Qingbo, Guo, Xiaogang. . CircARCN1 aggravates atherosclerosis by regulating HuR-mediated USP31 mRNA in macrophages. In Cardiovascular research, 120, 1531-1549. doi:10.1093/cvr/cvae148. https://pubmed.ncbi.nlm.nih.gov/39028686/

2. Hou, Yaoyao, Fan, Yingjun, Xia, Xian, Liu, Xixia, Chen, Xinpeng. . USP31 acetylation at Lys1264 is essential for its activity and cervical cancer cell growth. In Acta biochimica et biophysica Sinica, 53, 1037-1043. doi:10.1093/abbs/gmab080. https://pubmed.ncbi.nlm.nih.gov/34184746/

3. Ma, Qi, Ruan, Hongyu, Dai, Huihui, Yao, Wei-Dong. 2023. USP48/USP31 Is a Nuclear Deubiquitinase that Potently Regulates Synapse Remodeling. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.09.19.558317. https://pubmed.ncbi.nlm.nih.gov/37781625/

4. Li, Lan, Ye, Limin, Cui, Yinying, Zong, Zheng, Nie, Zhao. . USP31 Activates the Wnt/β-catenin Signaling Pathway and Promotes Gastric Cancer Cell Proliferation, Invasion and Migration. In Recent patents on anti-cancer drug discovery, 20, 232-247. doi:10.2174/0115748928297343240425055552. https://pubmed.ncbi.nlm.nih.gov/38715330/

5. Liang, Wenjun, Yang, Mingxia, Wang, Xiaohua, Xu, Ting, Zhang, Qian. . Deubiquitylase USP31 Induces Autophagy and Promotes the Progression in Lung Squamous Cell Carcinoma Cells by Stabilizing E2F1 Expression. In Current cancer drug targets, 24, 975-986. doi:10.2174/0115680096264557231124102054. https://pubmed.ncbi.nlm.nih.gov/38204265/

6. Zhang, Weitao, Lu, Junfeng, Feng, Lianshun, Yang, Zhiwei, Xu, Xiaojun. 2024. Sonic hedgehog-heat shock protein 90β axis promotes the development of nonalcoholic steatohepatitis in mice. In Nature communications, 15, 1280. doi:10.1038/s41467-024-45520-8. https://pubmed.ncbi.nlm.nih.gov/38342927/