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- W4281875586 abstract "The ovarian-tumor-domain-containing deubiquitinases (OTUDs) block ubiquitin-dependent protein degradation and are involved in diverse signaling pathways. We discovered a rare OTUD3 c.863G>A mutation in a family with an early age of onset of diabetes. This mutation reduces the stability and catalytic activity of OTUD3. We next constructed an experiment with Otud3−/− mice and found that they developed worse obesity, dyslipidemia, and insulin resistance than wild-type mice when challenged with a high-fat diet (HFD). We further found that glucose and fatty acids stimulate CREB-binding-protein-dependent OTUD3 acetylation, promoting its nuclear translocation, where OTUD3 regulates various genes involved in glucose and lipid metabolism and oxidative phosphorylation by stabilizing peroxisome-proliferator-activated receptor delta (PPARδ). Moreover, targeting PPARδ using a specific agonist can partially rescue the phenotype of HFD-fed Otud3−/− mice. We propose that OTUD3 is an important regulator of energy metabolism and that the OTUD3 c.863G>A is associated with obesity and a higher risk of diabetes." @default.
- W4281875586 created "2022-06-13" @default.
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- W4281875586 date "2022-07-01" @default.
- W4281875586 modified "2023-10-17" @default.
- W4281875586 title "Deubiquitinase OTUD3 regulates metabolism homeostasis in response to nutritional stresses" @default.
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- W4281875586 doi "https://doi.org/10.1016/j.cmet.2022.05.005" @default.
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