Observatorio de I+D+i UPM

Memorias de investigación
Research Publications in journals:
Regulation of OGT by URI in Response to Glucose Confers c-MYC-Dependent Survival Mechanisms.
Year:2016
Research Areas
  • Natural sciences and health sciences
Information
Abstract
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.
International
Si
JCR
Si
Title
Cancer Cell
ISBN
1535-6108
Impact factor JCR
23,214
Impact info
Volume
Journal number
From page
290
To page
307
Month
SIN MES
Ranking
Q1
Participants
  • Autor: Nils Stefan Buren (UPM)
  • Autor: Ana L. Gomes (CNIO)
  • Autor: Ana Teijeiro (CNIO)
  • Autor: Mohamad-Ali Fawal (CNIO)
  • Autor: Mahmut Yilmaz (CNIO)
  • Autor: Krishna S Tummala (CNIO)
  • Autor: Manuel Perez (CNIO)
  • : Manuel Rodriguez-Justo (CNIO)
  • Autor: Ramon Campos-Olivas (CNIO)
  • Autor: Diego Megías (CNIO)
  • Autor: Nabil Djouder (CNIO)
Research Group, Departaments and Institutes related
  • Creador: Grupo de Investigación: BIOLOGÍA MOLECULAR Y COMPUTACIONAL
S2i 2020 Observatorio de investigación @ UPM con la colaboración del Consejo Social UPM
Cofinanciación del MINECO en el marco del Programa INNCIDE 2011 (OTR-2011-0236)
Cofinanciación del MINECO en el marco del Programa INNPACTO (IPT-020000-2010-22)