2026-04-27T03:43:16Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/174012024-11-29T19:04:55Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Burén, Stefan author Gomes, Ana L author Teijeiro, Ana author Fawal, Mohamad-Ali author Yilmaz, Mahmut author Tummala, Krishna S author Perez, Manuel author Rodriguez-Justo, Manuel author Campos Olivas, Ramon author Megias Vazquez, Diego author Djouder, Nabil author 2016-08-08 Cancer 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. Cancer Cell. 2016 ;30(2):290-307. http://hdl.handle.net/20.500.12105/17401 27505673 10.1016/j.ccell.2016.06.023 1878-3686 Cancer cell Regulation of OGT by URI in Response to Glucose Confers c-MYC-Dependent Survival Mechanisms.