ArticleCancer discovery2019
Mutant and Wild-Type Isocitrate Dehydrogenase 1 Share Enhancing Mechanisms Involving Distinct Tyrosine Kinase Cascades in Cancer.
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Article in Cancer discovery, 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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21 citing papers in PubMed, 28 citations in OpenAlex.
- Expression, Purification, and Characterization of Recombinant Isocitrate Dehydrogenase (IDH) from Yarrowia lipolytica and its Application as a Protein Template for In Situ Synthesis of Gold Nanoparticles.The protein journal · 2026Article
- Autopalmitoylation of IDH1-R132H regulates its neomorphic activity in cancer cells.Nature chemical biology · 2026Article
- Mitochondria: from powerhouses of cells to hubs in antitumor immunity.Frontiers in immunology · 2026Review
- One size does not fit all: A comparative framework for optimizing ribonucleic acid transfection across acute myeloid leukemia cell lines.Biology methods & protocols · 2026Article
- Effects of aging and anti-aging dietary restriction on regulators of the [NADPH]/[NADPFree radical biology & medicine · 2025Review
- Study on the phosphorylation of NADJournal of enzyme inhibition and medicinal chemistry · 2025Article
- Crotonylation of IDH1 alleviates MASLD progression by enhancing the TCA cycle.Nature communications · 2025Article
- Structural and systems characterization of phosphorylation on metabolic enzymes identifies sex-specific metabolic reprogramming in obesity.Molecular cell · 2025Article
- OXPHOS mediators in acute myeloid leukemia patients: Prognostic biomarkers and therapeutic targets for personalized medicine.World journal of surgical oncology · 2024Article
- Silybin suppresses ovarian cancer cell proliferation by inhibiting isocitrate dehydrogenase 1 activity.Cancer science · 2022Article
- Cellular signals converge at the NOX2-SHP-2 axis to induce reductive carboxylation in cancer cells.Cell chemical biology · 2022Article
- The hallmarks of cancer metabolism: Still emerging.Cell metabolism · 2022Review
- ROS-regulated phosphorylation of ITPKB by CAMK2G drives cisplatin resistance in ovarian cancer.Oncogene · 2022Article
- Clinically Relevant Oxygraphic Assay to Assess Mitochondrial Energy Metabolism in Acute Myeloid Leukemia Patients.Cancers · 2021Article
- Lysine acetylation restricts mutant IDH2 activity to optimize transformation in AML cells.Molecular cell · 2021Article
- Evaluating Mechanisms of IDH1 Regulation through Site-Specific Acetylation Mimics.Biomolecules · 2021Article
- Exosomal IDH1 increases the resistance of colorectal cancer cells to 5-Fluorouracil.Journal of Cancer · 2021Article
- Metabolite sensing and signaling in cancer.The Journal of biological chemistry · 2020Review
- Article
- Metabolic Diversity in Human Non-Small Cell Lung Cancer Cells.Molecular cell · 2019Article
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Authors and funding
27 authors at 7 institutions in 2 countries.
Dong Chen *Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia.
Siyuan Xia *Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia.
Mei Wang *Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia.ORCID 0000-0001-7667-9118
Ruiting LinDepartment of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia.
Yuancheng LiWinship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia.ORCID 0000-0001-7410-0176
Hui MaoWinship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia.ORCID 0000-0002-0147-6022
Mike AguiarCell Signaling Technology, Inc., Danvers, Massachusetts.
Christopher A FamulareMemorial Sloan Kettering Cancer Center, New York, New York.
Alan H ShihMemorial Sloan Kettering Cancer Center, New York, New York.
Cameron W BrennanMemorial Sloan Kettering Cancer Center, New York, New York.
Xue GaoDepartment of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia.
Yaozhu PanDepartment of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia.
Shuangping LiuDepartment of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia.
Jun FanWinship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia.
Lingtao JinDepartment of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia.
Lina SongDepartment of Neurobiology, Morehouse School of Medicine, Atlanta, Georgia.
An ZhouDepartment of Neurobiology, Morehouse School of Medicine, Atlanta, Georgia.ORCID 0000-0002-9358-8012
Joydeep MukherjeeDepartment of Neurological Surgery, University of California, San Francisco, California.
Russell O PieperDepartment of Neurological Surgery, University of California, San Francisco, California.
Ashutosh MishraDepartment of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee.
Junmin PengDepartment of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee.
Martha ArellanoDepartment of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia.
William G BlumDepartment of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia.
Sagar LonialDepartment of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia.
Titus J BoggonDepartment of Pharmacology, Yale University School of Medicine, New Haven, Connecticut.
Ross L LevineMemorial Sloan Kettering Cancer Center, New York, New York. leviner@mskcc.org jchen@emory.edu.
Jing ChenDepartment of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia. leviner@mskcc.org jchen@emory.edu.
Emory University · USKettering University · USMorehouse School of Medicine · USNeurological Surgery · USSt. Jude Children's Research Hospital · USCell Signaling Technology (United States) · USYale University · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4MSynergistic role of signaling and epigenetics in leukemic transformationR35CA197594 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI Ross L Levine · 2017 to 2026
$11.4MRole of TET2 mutations in malignant transformation and acute myeloid leukemiaR01CA173636 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI AIFANTIS, IANNIS, LEVINE, ROSS L · 2013 to 2022
$6.3MTyrosine Kinase Signaling in Cancer Cell MetabolismR01CA140515 · NCI · UNIVERSITY OF CHICAGO · PI Jing Chen · 2010 to 2026
$5.4MSignaling and Targeting of 6-Phosphogluconate Dehydrogenase in Human CancersR01CA174786 · NCI · UNIVERSITY OF CHICAGO · PI CHEN, JING · 2014 to 2024
$3.7MMR Investigation of IDH Mutation and Its Marker 2-HG in Brain Tumor PatientsR01CA169937 · NCI · EMORY UNIVERSITY · PI MAO, HUI · 2013 to 2017
$1.9MMitochondrial acetyl-CoA acetyltransferase 1 promotes the Warburg effectR01CA183594 · NCI · EMORY UNIVERSITY · PI CHEN, JING · 2014 to 2018
$1.6MSignaling and targeting of FGFR1 fusions in 8p11 myeloproliferative syndromeR01CA120272 · NCI · EMORY UNIVERSITY · PI CHEN, JING · 2006 to 2010
$1.3MAnalysis of TET2 function in acute leukemiaK08CA181507 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI SHIH, ALAN · 2016 to 2020
$900kNCI NIH HHS K08 CA181507NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA120272NCI NIH HHS R01 CA140515NCI NIH HHS R01 CA169937NCI NIH HHS R01 CA173636NCI NIH HHS R01 CA174786NCI NIH HHS R01 CA183594NCI NIH HHS R35 CA197594
Abstract
Isocitrate dehydrogenase 1 (IDH1) is important for reductive carboxylation in cancer cells, and the IDH1 R132H mutation plays a pathogenic role in cancers including acute myeloid leukemia (AML). However, the regulatory mechanisms modulating mutant and/or wild-type (WT) IDH1 function remain unknown. Here, we show that two groups of tyrosine kinases (TK) enhance the activation of mutant and WT IDH1 through preferential Y42 or Y391 phosphorylation. Mechanistically, Y42 phosphorylation occurs in IDH1 monomers, which promotes dimer formation with enhanced substrate (isocitrate or α-ketoglutarate) binding, whereas Y42-phosphorylated dimers show attenuated disruption to monomers. Y391 phosphorylation occurs in both monomeric and dimeric IDH1, which enhances cofactor (NADP
Indexed as
MutationCell Line, TumorDisease Managementfms-Like Tyrosine Kinase 3HumansIsocitrate DehydrogenaseJanus Kinase 2Models, BiologicalNADPNeoplasmsPhosphorylationProtein BindingProtein MultimerizationProtein-Tyrosine KinasesFLT3 protein, humanfms-Like Tyrosine Kinase 3IDH1 protein, humanIsocitrate DehydrogenaseJAK2 protein, humanJanus Kinase 2NADPProtein-Tyrosine Kinases
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