ArticleNucleic acids research2016
Nuclear pyruvate kinase M2 complex serves as a transcriptional coactivator of arylhydrocarbon receptor.
Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 97 citations in OpenAlex.
- Article
- VB5 modulates osteoclast metabolic reprogramming and suppresses differentiation by blocking PKM2 nuclear translocation.Scientific reports · 2026Article
- A neutrophil-intrinsic CKLF1-PKM2 axis drives glycolytic flux for de novo DAG synthesis and pro-inflammatory ROS production.Cell death and differentiation · 2026Article
- Small but mighty: mitochondrial DNA at the centre of retrograde signalling.Cell communication and signaling : CCS · 2026Review
- Hallmarks of nuclear metabolism: implications for genome integrity, nuclear signaling, and therapeutic targeting.npj metabolic health and disease · 2026Review
- Metabolic enzyme-associated protein-protein interactions (mPPIs) in cancer: potential vulnerability for cancer treatment?Acta pharmacologica Sinica · 2025Review
- Loss of Dioxin Response Element-Mediated Induction of PKM2 Reprograms Hepatic Metabolism in Response to TCDD.International journal of molecular sciences · 2025Article
- Interplay of YEATS2 and GCDH regulates histone crotonylation and drives EMT in head and neck cancer.eLife · 2025Article
- Histone acetyltransferase HAF2 associates with pyruvate dehydrogenase complex to control H3K14ac and H3K23ac in ethylene response.Cell reports · 2025Article
- Dynamics of the mammalian pyruvate dehydrogenase complex revealed by in-situ structural analysis.Nature communications · 2025Article
- Effect of SNORD113-3/ADAR2 on glycolipid metabolism in glioblastoma via A-to-I editing of PHKA2.Cellular & molecular biology letters · 2025Article
- The role and regulatory mechanisms of the TCA cycle in early embryonic development.Frontiers in cell and developmental biology · 2025Review
- The role and therapeutic potential of glucose metabolism in multidrug resistance of cancer.Frontiers in cell and developmental biology · 2025Review
- New insights into coordinated regulation of AHR promoter transcription; molecular mechanisms and therapeutic targets.International journal of biological sciences · 2025Review
- Review
- LncRNA-Mediated TPI1 and PKM2 Promote Self-Renewal and Chemoresistance in GBM.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Disruption of canonical AHR-mediated induction of hepatocyte PKM2 expression compromises antioxidant defenses and increases TCDD-induced hepatotoxicity.Redox biology · 2024Article
- Chemotherapy-induced acetylation of ACLY by NAT10 promotes its nuclear accumulation and acetyl-CoA production to drive chemoresistance in hepatocellular carcinoma.Cell death & disease · 2024Article
- Nuclear pyruvate dehydrogenase complex regulates histone acetylation and transcriptional regulation in the ethylene response.Science advances · 2024Article
- Cuproptosis-related gene DLAT is a biomarker of the prognosis and immune microenvironment of gastric cancer and affects the invasion and migration of cells.Cancer medicine · 2024Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pyruvate kinase M2 (PKM2) and pyruvate dehydrogenase complex (PDC) regulate production of acetyl-CoA, which functions as an acetyl donor in diverse enzymatic reactions, including histone acetylation. However, the mechanism by which the acetyl-CoA required for histone acetylation is ensured in a gene context-dependent manner is not clear. Here we show that PKM2, the E2 subunit of PDC and histone acetyltransferase p300 constitute a complex on chromatin with arylhydrocarbon receptor (AhR), a transcription factor associated with xenobiotic metabolism. All of these factors are recruited to the enhancer of AhR-target genes, in an AhR-dependent manner. PKM2 contributes to enhancement of transcription of cytochrome P450 1A1 (CYP1A1), an AhR-target gene, acetylation at lysine 9 of histone H3 at the CYP1A1 enhancer. Site-directed mutagenesis of PKM2 indicates that this enhancement of histone acetylation requires the pyruvate kinase activity of the enzyme. Furthermore, we reveal that PDC activity is present in nuclei. Based on these findings, we propose a local acetyl-CoA production system in which PKM2 and PDC locally supply acetyl-CoA to p300 from abundant PEP for histone acetylation at the gene enhancer, and our data suggest that PKM2 sensitizes AhR-mediated detoxification in actively proliferating cells such as cancer and fetal cells.
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