{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Dexter JP"],"funding":["Massachusetts Institute of Technology","Penn | Perelman School of Medicine, University of Pennsylvania","Howard Hughes Medical Institute","EIF | Stand Up To Cancer","HHS | NIH | National Cancer Institute","National Science Foundation"],"pagination":["20051-20061"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6311528"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["293(52)"],"pubmed_abstract":["Monoallelic point mutations in the gene encoding the cytosolic, NADP<sup>+</sup>-dependent enzyme isocitrate dehydrogenase 1 (IDH1) cause increased production of the oncometabolite 2-hydroxyglutarate (2-HG) in multiple cancers. Most IDH1 mutant tumors retain one wildtype (WT) <i>IDH1</i> allele. Several studies have proposed that retention of this WT allele is protumorigenic by facilitating substrate channeling through a WT-mutant IDH1 heterodimer, with the WT subunit generating a local supply of α-ketoglutarate and NADPH that is then consumed by the mutant subunit to produce 2-HG. Here, we confirmed that coexpression of WT and mutant IDH1 subunits leads to formation of WT-mutant hetero-oligomers and increases 2-HG production. An analysis of a recently reported crystal structure of the WT-"],"journal":["The Journal of biological chemistry"],"pubmed_title":["Lack of evidence for substrate channeling or flux between wildtype and mutant isocitrate dehydrogenase to produce the oncometabolite 2-hydroxyglutarate."],"pmcid":["PMC6311528"],"funding_grant_id":["Center for Precision Medicine","1462629","Graduate Research Fellowship GE1144152","Medical Scientist Training Program"],"pubmed_authors":["Vander Heiden MG","Hosios AM","Dexter JP","Gunawardena J","Dasgupta T","Ward PS"],"additional_accession":[]},"is_claimable":false,"name":"Lack of evidence for substrate channeling or flux between wildtype and mutant isocitrate dehydrogenase to produce the oncometabolite 2-hydroxyglutarate.","description":"Monoallelic point mutations in the gene encoding the cytosolic, NADP<sup>+</sup>-dependent enzyme isocitrate dehydrogenase 1 (IDH1) cause increased production of the oncometabolite 2-hydroxyglutarate (2-HG) in multiple cancers. Most IDH1 mutant tumors retain one wildtype (WT) <i>IDH1</i> allele. Several studies have proposed that retention of this WT allele is protumorigenic by facilitating substrate channeling through a WT-mutant IDH1 heterodimer, with the WT subunit generating a local supply of α-ketoglutarate and NADPH that is then consumed by the mutant subunit to produce 2-HG. Here, we confirmed that coexpression of WT and mutant IDH1 subunits leads to formation of WT-mutant hetero-oligomers and increases 2-HG production. An analysis of a recently reported crystal structure of the WT-","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 Dec","modification":"2026-05-04T10:22:22.974Z","creation":"2025-02-19T03:39:59.687Z"},"accession":"S-EPMC6311528","cross_references":{"pubmed":["30381394"],"doi":["10.1074/jbc.ra118.004278","10.1074/jbc.RA118.004278"]}}