Evidence map›Paper›PMID 30862724›Full record

ArticleCancer discovery2019

Mutant and Wild-Type Isocitrate Dehydrogenase 1 Share Enhancing Mechanisms Involving Distinct Tyrosine Kinase Cascades in Cancer.

Dong Chen, Siyuan Xia, Mei Wang, Ruiting Lin, Yuancheng Li, Hui Mao, Mike Aguiar, Christopher A Famulare, Alan H Shih, Cameron W Brennan and 17 more

Open access · greenAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.8field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
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  5. Review
  6. Study on the phosphorylation of NADJournal of enzyme inhibition and medicinal chemistry · 2025
    Article
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  18. Metabolite sensing and signaling in cancer.The Journal of biological chemistry · 2020
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

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
$347.4M
Synergistic role of signaling and epigenetics in leukemic transformationR35CA197594 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI Ross L Levine · 2017 to 2026
$11.4M
Role 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
$6.3M
Tyrosine Kinase Signaling in Cancer Cell MetabolismR01CA140515 · NCI · UNIVERSITY OF CHICAGO · PI Jing Chen · 2010 to 2026
$5.4M
Signaling and Targeting of 6-Phosphogluconate Dehydrogenase in Human CancersR01CA174786 · NCI · UNIVERSITY OF CHICAGO · PI CHEN, JING · 2014 to 2024
$3.7M
MR Investigation of IDH Mutation and Its Marker 2-HG in Brain Tumor PatientsR01CA169937 · NCI · EMORY UNIVERSITY · PI MAO, HUI · 2013 to 2017
$1.9M
Mitochondrial acetyl-CoA acetyltransferase 1 promotes the Warburg effectR01CA183594 · NCI · EMORY UNIVERSITY · PI CHEN, JING · 2014 to 2018
$1.6M
Signaling and targeting of FGFR1 fusions in 8p11 myeloproliferative syndromeR01CA120272 · NCI · EMORY UNIVERSITY · PI CHEN, JING · 2006 to 2010
$1.3M
Analysis of TET2 function in acute leukemiaK08CA181507 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI SHIH, ALAN · 2016 to 2020
$900k
NCI 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
6 · The paper itself

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

Identifiers

PMID30862724
PMCPMC6548588
OpenAlexW2921054431

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.