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Descripción
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| 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, PP1g, and OGT, the enzyme catalyzing O-GlcNAcylation. Glucose deprivation induces the activation of PKA, which phosphorylates URI at Ser-371, resulting in PP1g 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, PP1g-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. | |
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Internacional
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Si |
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JCR del ISI
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Si |
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Título de la revista
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Cancer Cell |
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ISSN
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1535-6108 |
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Factor de impacto JCR
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23,214 |
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Información de impacto
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Volumen
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DOI
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Número de revista
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Desde la página
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290 |
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Hasta la página
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307 |
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Mes
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SIN MES |
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Ranking
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Q1 |