The oncometabolite 2‐hydroxyglutarate inhibits histone lysine demethylases

By R. Chowdhury, K. Yeoh, Ya-min Tian, Lars Hillringhaus, Eleanor A. L. Bagg, N. R. Rose, Ivanhoe K. H. Leung, X. Li, E. Woon, Ming Yang and 8 more. EMBO Reports, 2011

1,001 citations recorded by the source corpus.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/e6bd34bdf5282202be386b2f353e072be7387c86

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Citations in the corpus

WT1 recruits TET2 to regulate its target gene expression and suppress leukemia cell proliferation (2015, positive): “…catalytically inactivated by D-2-hydroxyglutarate (D-2-HG), an oncometabolite produced by mutated isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) (Chowdhury et al., 2011; Xu et al., 2011), which occurs in about 20% of AMLs in a mutually exclusive manner with TET2 mutations (Figueroa et al.,…”
The role of mutations in epigenetic regulators in myeloid malignancies (2012, background): “In addition to inhibiting TET2 dioxygenase activity, 2-HG also inhibits other a-KG-dependent proteins, including members of the Jumonji-C (JMJC) domain histone demethylase family (61).”
LOSS OF 5-HYDROXYMETHYLCYTOSINE IS AN EPIGENETIC HALLMARK OF MELANOMA (2012, background): “…Surgery and Medicine, Weill Cornell Medical College and New York Presbyterian Hospital, New York, NY 10065, USA 13These authors contributed equally to this work *Correspondence: gmurphy@rics.bwh.harvard.edu (G.F.M.), yujiang_shi@hms.harvard.edu (Y.G.S.) http://dx.doi.org/10.1016/j.cell.2012.07.033”
Influence of Metabolism on Epigenetics and Disease (2013, positive): “R-2HG, succinate, and fumarate are all capable of inhibiting multiple 2-oxoglutarate-dependent dioxygenases, including the JmjC histone demethylases and TET proteins, when present at sufficiently high concentrations (Figure 6B) (Cervera et al., 2009; Chowdhury et al., 2011; Figueroa et al., 2010; Ko”
R-2HG Exhibits Anti-tumor Activity by Targeting FTO/m6A/MYC/CEBPA Signaling (2017, background): “R-2HG has also been shown to competitively inhibit the functions of DNA and histone demethylases, such as TET2, JMJD, and KDM, leading to hypermethylated DNA and histones (Chowdhury et al., 2011; Sasaki et al., 2012).”
Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma. (2012, background): “Methylation of K27 and K36 is also disrupted by elevated levels of the onco-metabolite 2-hydroxyglutarate (2-HG) resulting from gain-of-function mutations in IDH1 (Chowdhury et al., 2011; Xu et al., 2011), which was previously shown to be associated with a distinct Glioma-CpG-Island Methylator Pheno”
Metabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not Anticipate (2012, background): “Although one initial report implicated a broad array of enzymes that were affected by 2HG (Xu et al., 2011), a later report suggested greater specificity of 2HG for some specific Jumonji C domain histone demethylases (Chowdhury et al., 2011).”
Targeting Metabolism for Cancer Therapy (2017, background): “At these high concentrations, D-2HG can inhibit αKG-dependent dioxygenases, including enzymes involved in histone and DNA demethylation (Chowdhury et al., 2011; Janke et al., 2017; Koivunen et al., 2012; Xu et al., 2011).”
Metabolic regulation of epigenetics (2012, background): “Biochemical studies suggest that 2HG can inhibit a number of aKG-dependent enzymes with varying potencies, therefore the challenge is to identify key enzymes that mediate 2HG’s oncogenic effect (Chowdhury et al., 2011; Xu et al., 2011b).”
Metabolic reprogramming and epigenetic modifications on the path to cancer (2021, background): “There are two enantiomeric forms of 2HG, D-(or R-) and L-(or S-) type 2-HG, all of which are α-KG inhibitors that inhibit α-KG-dependent histone lysine demethylases, such as FIH (factor inhibiting HIF), PHD2 (prolyl hydroxylase domain-containing protein, also known as HIF prolyl-hydroxylase 2), and ”