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PTEN Suppresses Glycolysis by Dephosphorylating and Inhibiting Autophosphorylated PGK1.

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机构: [1]Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China [2]Institute for Brain Tumors, Jiangsu Key Lab of Cancer Biomarkers, Prevention, and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu 211166, China [3]Brain Tumor Center and Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA [4]CAS Key Laboratory of Infection and Immunity, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China [5]Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China [6]Department of Bioinformatics & Computational Biology, Proteomics and Metabolomics Core Facility, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA [7]School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China [8]MOEKey Laboratory of Protein Sciences, Beijing Advanced Innovation Center for Structural Biology, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China [9]Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China [10]Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China [11]The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan 450052, China [12]Department of Pathology, University of Iowa, Iowa City, IA 52242, USA [13]Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310029, China
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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. Copyright © 2019 Elsevier Inc. All rights reserved.

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大类 | 1 区 生物
小类 | 1 区 生化与分子生物学 1 区 细胞生物学
最新[2023]版:
大类 | 1 区 生物学
小类 | 1 区 生化与分子生物学 1 区 细胞生物学
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第一作者机构: [1]Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China [2]Institute for Brain Tumors, Jiangsu Key Lab of Cancer Biomarkers, Prevention, and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu 211166, China [3]Brain Tumor Center and Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
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通讯机构: [1]Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China [2]Institute for Brain Tumors, Jiangsu Key Lab of Cancer Biomarkers, Prevention, and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu 211166, China [3]Brain Tumor Center and Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA [13]Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310029, China
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