Burén, StefanGomes, Ana LTeijeiro, AnaFawal, Mohamad-AliYilmaz, MahmutTummala, Krishna SPerez, ManuelRodriguez-Justo, ManuelCampos Olivas, RamonMegias Vazquez, DiegoDjouder, Nabil2024-02-012024-02-012016-08-08Cancer Cell. 2016 ;30(2):290-307.http://hdl.handle.net/20.500.12105/17401Cancer cells can adapt and survive under low nutrient conditions, but underlying mechanisms remain poorly explored. We demonstrate here that glucose maintains a functional complex between the co-chaperone URI, PP1γ, and OGT, the enzyme catalyzing O-GlcNAcylation. Glucose deprivation induces the activation of PKA, which phosphorylates URI at Ser-371, resulting in PP1γ release and URI-mediated OGT inhibition. Low OGT activity reduces O-GlcNAcylation and promotes c-MYC degradation to maintain cell survival. In the presence of glucose, PP1γ-bound URI increases OGT and c-MYC levels. Accordingly, mice expressing non-phosphorylatable URI (S371A) in hepatocytes exhibit high OGT activity and c-MYC stabilization, accelerating liver tumorigenesis in agreement with c-MYC oncogenic functions. Our work uncovers that URI-regulated OGT confers c-MYC-dependent survival functions in response to glucose fluctuations.engVoRhttp://creativecommons.org/licenses/by-nc-nd/4.0/AnimalsGlucoseGlucose Tolerance TestHEK293 CellsHeLa CellsHumansAttribution-NonCommercial-NoDerivatives 4.0 Internacional2750567330229010.1016/j.ccell.2016.06.0231878-3686Cancer cellopen access