ArticleMolecular cell2021
Lysine acetylation restricts mutant IDH2 activity to optimize transformation in AML cells.
Article in Molecular cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 24 citations in OpenAlex.
- Corylin promotes healthy aging via RAGA-mTOR suppression and sex-dependent activation of SIRT3.Nature communications · 2026Article
- SIRT3 suppresses renal cancer progression by regulating IDH2 acetylation.Scientific reports · 2026Article
- Atlas of lysine acetylation in the mouse.bioRxiv : the preprint server for biology · 2026Article
- IDH2 lactylation promotes angiogenesis in murine diabetic myocardial infarction via blocking Cav1-eNOS interaction.Nature communications · 2025Article
- Study on the phosphorylation of NADJournal of enzyme inhibition and medicinal chemistry · 2025Article
- Review
- Crotonylation of IDH1 alleviates MASLD progression by enhancing the TCA cycle.Nature communications · 2025Article
- Hyperglycemia-induced Sirt3 downregulation increases microglial aerobic glycolysis and inflammation in diabetic neuropathic pain pathogenesis.CNS neuroscience & therapeutics · 2024Article
- Biomimetic Synthesis and Chemical Proteomics Reveal the Mechanism of Action and Functional Targets of Phloroglucinol Meroterpenoids.Journal of the American Chemical Society · 2024Article
- Targeting ACAT1 in cancer: from threat to treatment.Frontiers in oncology · 2024Review
- From mitochondria to tumor suppression: ACAT1's crucial role in gastric cancer.Frontiers in immunology · 2024Article
- Bidirectional interplay between metabolism and epigenetics in hematopoietic stem cells and leukemia.The EMBO journal · 2023Review
- ACAT1 deficiency in myeloid cells promotes glioblastoma progression by enhancing the accumulation of myeloid-derived suppressor cells.Acta pharmaceutica Sinica. B · 2023Article
- Cryopreservation Induces Acetylation of Metabolism-Related Proteins in Boar Sperm.International journal of molecular sciences · 2023Article
- Article
- Small molecule metabolites: discovery of biomarkers and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- SIRT1 activation synergizes with FXR agonism in hepatoprotectionActa pharmaceutica Sinica. B · 2023Article
- Nicotinamide Mononucleotide Administration Amends Protein Acetylome of Aged Mouse Liver.Cells · 2022Article
- The Crucial Roles of Intermediate Metabolites in Cancer.Cancer management and research · 2021Review
Corrections and comments
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Authors and funding
25 authors at 5 institutions in 1 country.
Funding
Abstract
Mutant isocitrate dehydrogenase (IDH) 1 and 2 play a pathogenic role in cancers, including acute myeloid leukemia (AML), by producing oncometabolite 2-hydroxyglutarate (2-HG). We recently reported that tyrosine phosphorylation activates IDH1 R132H mutant in AML cells. Here, we show that mutant IDH2 (mIDH2) R140Q commonly has K413 acetylation, which negatively regulates mIDH2 activity in human AML cells by attenuating dimerization and blocking binding of substrate (α-ketoglutarate) and cofactor (NADPH). Mechanistically, K413 acetylation of mitochondrial mIDH2 is achieved through a series of hierarchical phosphorylation events mediated by tyrosine kinase FLT3, which phosphorylates mIDH2 to recruit upstream mitochondrial acetyltransferase ACAT1 and simultaneously activates ACAT1 and inhibits upstream mitochondrial deacetylase SIRT3 through tyrosine phosphorylation. Moreover, we found that the intrinsic enzyme activity of mIDH2 is much higher than mIDH1, thus the inhibitory K413 acetylation optimizes leukemogenic ability of mIDH2 in AML cells by both producing sufficient 2-HG for transformation and avoiding cytotoxic accumulation of intracellular 2-HG.
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Registered trials
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.