ArticleCommunications biology2019
Mutations in the PKM2 exon-10 region are associated with reduced allostery and increased nuclear translocation.
Article in Communications biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
- KDM8/c-Myc axis-mediated glucose metabolism reprogramming promotes the progression of ovarian cancer.Scientific reports · 2026Article
- Unveiling the inhibitory effects of tannic acid and doxorubicin combination on pyruvate kinase M2 in breast cancer cells.Frontiers in pharmacology · 2026Article
- The CLIC1-PKM2 axis orchestrates glycolytic metabolism to accelerate gastric cancer progression.Journal of translational medicine · 2025Article
- Nuclear PKM2: a signal receiver, a gene programmer, and a metabolic modulator.Journal of biomedical science · 2025Review
- PSD3, regulated by PKM2, endows growth and metastasis advantages in esophageal squamous cell carcinoma by modulating EMT progression.Scientific reports · 2025Article
- Glycolysis reprogramming in CAFs promotes oxaliplatin resistance in pancreatic cancer through circABCC4 mediated PKM2 nuclear translocation.Cell death & disease · 2025Article
- Extracellular PKM2 Preserves Cardiomyocytes and Reduces Cardiac Fibrosis During Myocardial Infarction.International journal of molecular sciences · 2024Article
- PYK-SubstitutionOME: an integrated database containing allosteric coupling, ligand affinity and mutational, structural, pathological, bioinformatic and computational information about pyruvate kinase isozymes.Database : the journal of biological databases and curation · 2023Article
- Warburg-like metabolic transformation underlies neuronal degeneration in sporadic Alzheimer's disease.Cell metabolism · 2022Article
- Disease-related protein co-expression networks are associated with the prognosis of resectable node-positive pancreatic ductal adenocarcinoma.Scientific reports · 2022Article
- Nuclear TIGAR mediates an epigenetic and metabolic autoregulatory loopActa pharmaceutica Sinica. B · 2022Article
- Probing altered enzyme activity in the biochemical characterization of cancer.Bioscience reports · 2022Review
- Targeting Mitochondrial OXPHOS and Their Regulatory Signals in Prostate Cancers.International journal of molecular sciences · 2021Review
- Prognostic Significance ofDiagnostics (Basel, Switzerland) · 2021Article
- The Role of PKM2 in Metabolic Reprogramming: Insights into the Regulatory Roles of Non-Coding RNAs.International journal of molecular sciences · 2021Review
- Role of PKM2-Mediated Immunometabolic Reprogramming on Development of Cytokine Storm.Frontiers in immunology · 2021Review
- Mechanism of PKM2 affecting cancer immunity and metabolism in Tumor Microenvironment.Journal of Cancer · 2021Review
- Structural basis for allosteric regulation of pyruvate kinase M2 by phosphorylation and acetylation.The Journal of biological chemistry · 2020Article
- Cell-Type Specific Metabolic Response of Cancer Cells to Curcumin.International journal of molecular sciences · 2020Article
- Glucose Metabolism on Tumor Plasticity, Diagnosis, and Treatment.Frontiers in oncology · 2020Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PKM2 is a key metabolic enzyme central to glucose metabolism and energy expenditure. Multiple stimuli regulate PKM2's activity through allosteric modulation and post-translational modifications. Furthermore, PKM2 can partner with KDM8, an oncogenic demethylase and enter the nucleus to serve as a HIF1α co-activator. Yet, the mechanistic basis of the exon-10 region in allosteric regulation and nuclear translocation remains unclear. Here, we determined the crystal structures and kinetic coupling constants of exon-10 tumor-related mutants (H391Y and R399E), showing altered structural plasticity and reduced allostery. Immunoprecipitation analysis revealed increased interaction with KDM8 for H391Y, R399E, and G415R. We also found a higher degree of HIF1α-mediated transactivation activity, particularly in the presence of KDM8. Furthermore, overexpression of PKM2 mutants significantly elevated cell growth and migration. Together, PKM2 exon-10 mutations lead to structure-allostery alterations and increased nuclear functions mediated by KDM8 in breast cancer cells. Targeting the PKM2-KDM8 complex may provide a potential therapeutic intervention.
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Registered trials
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