Yod1-KO Mouse

YOD1, a 38 kDa protein belonging to the ovarian tumour protease (OTU) family, is a deubiquitinase. Ubiquitination is a reversible process, and YOD1, as a deubiquitinating enzyme (DUB), plays a role in controlling the ubiquitin-proteasome system by cleaving the bond between ubiquitin and substrate proteins. It is involved in multiple pathways such as cell-cycle regulation, p53, β-catenin, extracellular-regulated signal kinase (ERK), and YES-associated pathway (YAP) activities, which are crucial for various biological processes and disease developments [5].

In triple-negative breast cancer (TNBC), YOD1 is upregulated and functions as an oncogene. Knockdown of YOD1 in TNBC cells inhibits cell migration, proliferation, cell cycle, and drug resistance both in vitro and in vivo. Mechanistically, it binds with CDK1, de-polyubiquitylates CDK1, and upregulates its expression [1].

In colitis, YOD1-deficient mice are highly susceptible to dextran sulfate sodium (DSS)-induced colitis. YOD1 from hematopoietic cells inhibits DSS colitis by promoting NOD2-mediated physiological inflammation in macrophages, through stabilizing RIPK2 [2].

In MRSA sepsis-induced disseminated intravascular coagulation (DIC), YOD1 deficiency enhances NLRP3 inflammasome activation and coagulation. YOD1 interacts with NLRP3 to remove K33-linked ubiquitination of NLRP3, inhibiting its expression and inflammasome activation [3].

In head and neck squamous cell carcinoma (HNSCC), YOD1 is downregulated. Depletion of YOD1 promotes HNSCC growth, invasion, and epithelial-mesenchymal transition. YOD1 inhibits the ERK/β-catenin pathway by suppressing the ubiquitination and degradation of TRIM33 [4].

In conclusion, YOD1 has diverse functions in different biological processes and disease conditions. Its role in maintaining protein stability through deubiquitination affects various cellular activities. Gene knockout models, such as those in TNBC, colitis, MRSA-induced DIC, and HNSCC studies, have revealed its importance in these disease areas, providing potential therapeutic targets for treatment.