Usp50, or ubiquitin specific peptidase 50, is a deubiquitinating enzyme. It plays crucial roles in multiple biological processes, interacting with various proteins and participating in pathways like DNA replication, inflammasome activation, and fatty acid oxidation. Its functions suggest it has overall importance in maintaining cellular homeostasis and is relevant in disease-associated processes [1,2,3]. Genetic models, such as gene knockout mouse models, can be valuable for studying Usp50's functions.

In duodenogastric reflux-induced gastric tumorigenesis, Usp50 deficiency led to reduced bile acid-induced NLRP3 inflammasome activation and HMGB1 release, indicating its role in promoting this tumorigenesis process through regulating the NLRP3 inflammasome [1]. In replication studies, cells lacking Usp50 showed increased association of DNA2 nuclease and RECQL4 and RECQL5 helicases, causing replication defects, highlighting its importance in maintaining proper replication fork functions [2,4]. In LPS-induced sepsis, knocking down Usp50 decreased CPT1a expression and fatty acid oxidation mediated by mitochondrial STAT3, showing its role in this sepsis-related metabolic process [3].

In conclusion, Usp50 is essential for processes like inflammasome activation, DNA replication, and fatty acid oxidation. Through gene knockout mouse models, its role in diseases such as gastric cancer, and potentially sepsis, has been revealed. Understanding Usp50's functions can provide new insights into disease mechanisms and potential treatment strategies for these related disease areas.

References:

1. Zhao, Chenye, Mu, Mingchao, Li, Xiaopeng, Sun, Xuejun, Yu, Junhui. 2024. USP50 regulates NLRP3 inflammasome activation in duodenogastric reflux-induced gastric tumorigenesis. In Frontiers in immunology, 15, 1326137. doi:10.3389/fimmu.2024.1326137. https://pubmed.ncbi.nlm.nih.gov/38469295/

2. Mackay, Hannah L, Stone, Helen R, Ronson, George E, Saponaro, Marco, Morris, Joanna R. 2024. USP50 suppresses alternative RecQ helicase use and deleterious DNA2 activity during replication. In Nature communications, 15, 8102. doi:10.1038/s41467-024-52250-4. https://pubmed.ncbi.nlm.nih.gov/39284827/

3. Li, Rongqing, Li, Xueqin, Zhao, Jie, Yang, Jing, Ikezoe, Takayuki. 2022. Mitochondrial STAT3 exacerbates LPS-induced sepsis by driving CPT1a-mediated fatty acid oxidation. In Theranostics, 12, 976-998. doi:10.7150/thno.63751. https://pubmed.ncbi.nlm.nih.gov/34976224/

4. Mackay, Hannah L, Stone, Helen R, Ellis, Katherine, Saponaro, Marco, Morris, Joanna R. 2024. USP50 suppresses alternative RecQ helicase use and deleterious DNA2 activity during replication. In bioRxiv : the preprint server for biology, , . doi:10.1101/2024.01.10.574674. https://pubmed.ncbi.nlm.nih.gov/38260523/