Mutant IDH inhibits HNF-4α to block hepatocyte differentiation and promote biliary cancer.

doi:10.1038/nature13441

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Article

Mutant IDH inhibits HNF-4α to block hepatocyte differentiation and promote biliary cancer.

Nature - 4 Sept 2014

Saha Supriya K, Parachoniak Christine A, Ghanta Krishna S, Fitamant Julien, Ross Kenneth N, Najem Mortada S, Gurumurthy Sushma, Akbay Esra A, Sia Daniela, Cornella Helena, Miltiadous Oriana, Walesky Chad, Deshpande Vikram, Zhu Andrew X, Hezel Aram F, Yen Katharine E, Straley Kimberly S, Travins Jeremy, Popovici-Muller Janeta, Gliser Camelia, Ferrone Cristina R, Apte Udayan, Llovet Josep M, Wong Kwok-Kin, Ramaswamy Sridhar, Bardeesy Nabeel

Abstract excerpt

Mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 are among the most common genetic alterations in intrahepatic cholangiocarcinoma (IHCC), a deadly liver cancer. Mutant IDH proteins in IHCC and other malignancies acquire an abnormal enzymatic activity allowing them to convert α-ketoglutarate (αKG) to 2-hydroxyglutarate (2HG), which inhibits the activity of multiple αKG-dependent dioxygenases, and results in...

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Identifiers

PMID: 25043045
DOI: 10.1038/nature13441
PMCID: PMC4499230

Genes

IDH1
IDH2

Provenance

PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 7 Sept 2026. Manifest publication-graph-cohort-2026-09-08.1.

Source receipt: pubmed, retrieved 7 Sept 2026.

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