| First Author | Shtraizent N | Year | 2017 |
| Journal | Elife | Volume | 6 |
| PubMed ID | 28644127 | Mgi Jnum | J:259883 |
| Mgi Id | MGI:6141099 | Doi | 10.7554/eLife.22477 |
| Citation | Shtraizent N, et al. (2017) MPI depletion enhances O-GlcNAcylation of p53 and suppresses the Warburg effect. Elife 6:e22477 |
| abstractText | Rapid cellular proliferation in early development and cancer depends on glucose metabolism to fuel macromolecule biosynthesis. Metabolic enzymes are presumed regulators of this glycolysis-driven metabolic program, known as the Warburg effect; however, few have been identified. We uncover a previously unappreciated role for Mannose phosphate isomerase (MPI) as a metabolic enzyme required to maintain Warburg metabolism in zebrafish embryos and in both primary and malignant mammalian cells. The functional consequences of MPI loss are striking: glycolysis is blocked and cells die. These phenotypes are caused by induction of p53 and accumulation of the glycolytic intermediate fructose 6-phosphate, leading to engagement of the hexosamine biosynthetic pathway (HBP), increased O-GlcNAcylation, and p53 stabilization. Inhibiting the HBP through genetic and chemical methods reverses p53 stabilization and rescues the Mpi-deficient phenotype. This work provides mechanistic evidence by which MPI loss induces p53, and identifies MPI as a novel regulator of p53 and Warburg metabolism. |
