PTEN Suppresses Glycolysis by Dephosphorylating and Inhibiting Autophosphorylated PGK1
Xu Qian, Xinjian Li, Zhumei Shi,Yan Xia, Qingsong Cai, Daqian Xu, Lin Tan, Linyong Du, Yanhua Zheng, Dan Zhao, Chuanbao Zhang, Philip L.Lorenzi, Yongping You, Bing-Hua Jiang, Tao Jiang, Haitao Li, Zhimin Lu
Summary
The PTEN tumor suppressor is frequently mutated or deleted in cancer and regulates glucose metabolism through the PI3K-AKT pathway. However, whether PTEN directly regulates glycolysis in tumor cells is unclear. We demonstrate here that PTEN directly interacts with phosphoglycerate kinase 1 (PGK1). PGK1 functions not only as a glycolytic enzyme but also as a protein kinase intermolecularly autophosphorylating itself at Y324 for activation. The protein phosphatase activity of PTEN dephosphorylates and inhibits autophosphorylated PGK1, thereby inhibiting glycolysis, ATP production, and brain tumor cell proliferation. In addition, knockin expression of a PGK1 Y324F mutant inhibits brain tumor formation. Analyses of human glioblastoma specimens reveals that PGK1 Y324 phosphorylation levels inversely correlate with PTEN expression status and are positively associated with poor prognosis in glioblastoma patients. This work highlights the instrumental role of PGK1 autophosphorylation in its activation and PTEN protein phosphatase activity in governing glycolysis and tumorigenesis.
附件下载：
PTEN Suppresses Glycolysis by Dephosphorylating and Inhibiting Autophosphorylated PGK1, Mol Cell, 7 Nov 2019
Molecular Cell, 7 November, 2019，DOI：https://doi.org/10.1016/j.molcel.2019.08.006
PTEN Suppresses Glycolysis by Dephosphorylating and Inhibiting Autophosphorylated PGK1
Xu Qian, Xinjian Li, Zhumei Shi,Yan Xia, Qingsong Cai, Daqian Xu, Lin Tan, Linyong Du, Yanhua Zheng, Dan Zhao, Chuanbao Zhang, Philip L.Lorenzi, Yongping You, Bing-Hua Jiang, Tao Jiang, Haitao Li, Zhimin Lu
Summary
The PTEN tumor suppressor is frequently mutated or deleted in cancer and regulates glucose metabolism through the PI3K-AKT pathway. However, whether PTEN directly regulates glycolysis in tumor cells is unclear. We demonstrate here that PTEN directly interacts with phosphoglycerate kinase 1 (PGK1). PGK1 functions not only as a glycolytic enzyme but also as a protein kinase intermolecularly autophosphorylating itself at Y324 for activation. The protein phosphatase activity of PTEN dephosphorylates and inhibits autophosphorylated PGK1, thereby inhibiting glycolysis, ATP production, and brain tumor cell proliferation. In addition, knockin expression of a PGK1 Y324F mutant inhibits brain tumor formation. Analyses of human glioblastoma specimens reveals that PGK1 Y324 phosphorylation levels inversely correlate with PTEN expression status and are positively associated with poor prognosis in glioblastoma patients. This work highlights the instrumental role of PGK1 autophosphorylation in its activation and PTEN protein phosphatase activity in governing glycolysis and tumorigenesis.
文章链接：https://www.sciencedirect.com/science/article/pii/S1097276519306227?via%3Dihub