OTUD1 (OTU Deubiquitinase 1)

OTUD1 cleaves the K63-linked ubiquitin chain of RAD23B and XPC, and enhances PRKN mediated K48-linked ubiquitination of RAD23B-XPC and the subsequent proteasomal degradation. The findings of this study highlighted that OTUD1 could be a potential therapeutic target for NSCLC.

Finally, silencing AMPKα2 in cardiomyocytes abolishes the cardioprotective effects of OTUD1 deficiency in diabetic mice. In conclusion, this work identifies a direct regulatory DUB of AMPK and presents a OTUD1-AMPK axis in cardiomyocytes for driving DCM.

Furthermore, we demonstrate that combining the methylation inhibitor Decitabine (DAC) with radiotherapy significantly improves treatment efficacy by overcoming radioresistance. These findings provide insights into NPC radioresistance and suggest that using DAC in combination with radiotherapy to target the TFAP2C-OTUD1-SLC25A11 axis could be a promising strategy to overcome radioresistance.

Overall, we demonstrate that OTUD1 interacts with STAT3 and deubiquitinates, inhibits its nuclear translocation and activity, and ultimately inhibits immune evasion of ccRCC by downregulating PD-L1.

In SAE, OTUD1 deubiquitinates HK2, promoting its dissociation from mitochondria, which triggers microglia pyroptosis, leading to neuronal damage and cognitive impairment.

In conclusion, OTUD1 may serve a protective role in COPD by inhibiting inflammation and reducing cell damage caused by cigarette smoke exposure. The suppression of OTUD1 through METTL3‑mediated m6A methylation and YTHDF2 interaction represents a novel mechanism contributing to COPD pathogenesis, suggesting potential therapeutic targets for mitigating disease progression.

Finally, silencing of RACK1 reverses OTUD1-promoted H/R induced myocardial apoptosis. In conclusion, our findings suggest that OTUD1 promotes I/R-induced heart injury by deubiquitinating RACK1, suggesting that OTUD1 is a potential therapeutic target for myocardial I/R.

In addition, bcOTUD1 could degrade bcIRF3/7 protein levels, while proteasome inhibitor MG132, lysosome inhibitor chloroquine and autophagy inhibitor 3-MA are able to restore this degradation. Co-immunoprecipitation assay has revealed that bcOTUD1 interacts with bcIRF3/7, and removes K63-linked ubiquitination of bcIRF3 and K48- and K63-linked ubiquitination of bcIRF7. To conclude, our research has brought to light for the first time in teleost that OTUD1 degrade IRF3/7 through decreasing their ubiquitination, thereby restraining IRF3/7-mediated antiviral immune response, which provides an important reference for the study of teleost interferon signaling.

These findings elucidate the OTUD1-β-catenin pathway's role in endothelial dysfunction-associated angiogenesis and suggest OTUD1 as a promising therapeutic target for diabetic non-healing wounds.

These events stopped the growth of lesions in vivo and reduced abdominal inflammation. The study demonstrated the critical role of the deubiquitinating enzyme OTUD1 in endometriosis, indicating its potential therapeutic effect on endometriosis.

Notably, the disruption of the positive feedback loop by targeting c-Jun or ASK1/JNK with T-5224, selonsertib, or ibrutinib markedly inhibited the leptin-induced stemness maintenance of OCSCs and tumorigenicity. Our findings reveal a crucial mechanism for leptin-mediated stemness maintenance and indicate that targeting c-Jun or the identified positive feedback loop has translational potential for ovarian cancer patients.

Consistently, the relative ubiquitination level of AP1G1 in goose fatty liver was lower than that of normal liver, which is correlated with increased protein abundance of AP1G1 and OTUD1 in goose fatty liver. In conclusion, the increased protein abundance of OTUD1 in goose fatty liver can regulate the expression of cytokines and related pathways during the formation of goose fatty liver by promoting the deubiquitination of the interacting proteins of OTUD1, including AP1G1.