| First Author | Burén S | Year | 2016 |
| Journal | Cancer Cell | Volume | 30 |
| Issue | 2 | Pages | 290-307 |
| PubMed ID | 27505673 | Mgi Jnum | J:234982 |
| Mgi Id | MGI:5792589 | Doi | 10.1016/j.ccell.2016.06.023 |
| Citation | Buren S, et al. (2016) Regulation of OGT by URI in Response to Glucose Confers c-MYC-Dependent Survival Mechanisms. Cancer Cell 30(2):290-307 |
| abstractText | 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, PP1gamma, and OGT, the enzyme catalyzing O-GlcNAcylation. Glucose deprivation induces the activation of PKA, which phosphorylates URI at Ser-371, resulting in PP1gamma 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, PP1gamma-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. |
