ArticleNature communications2021
Citrullination of pyruvate kinase M2 by PADI1 and PADI3 regulates glycolysis and cancer cell proliferation.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
- Role of the PADI family in inflammatory autoimmune diseases and cancers: A systematic review.Frontiers in immunology · 2023Pooled it
- Review
- Post-translational modifications in metabolic reprogramming: implications for metabolic therapy and immunotherapy in cancer.Signal transduction and targeted therapy · 2026Review
- Identification and external validation of a prognostic signature based on bone morphogenetic protein-related mRNAs for kidney renal clear cell carcinoma.Discover oncology · 2026Article
- Unveiling lactylation: A novel frontier in the pathogenesis of diabetic nephropathy (Review).International journal of molecular medicine · 2026Review
- Role of CHD4 in tumor progression, DNA damage response and treatment resistance (Review).Oncology reports · 2026Review
- ELK3 promotes cisplatin resistance in ovarian cancer via regulating CHD4 gene expression.Discover oncology · 2026Article
- BioGate SERS Chip enables robust metabolite-oriented nanobiotechnological detection of breast cancer margins.Journal of nanobiotechnology · 2026Article
- Identification of biomarkers for non-invasive diagnosis and risk stratification in prostate cancer using NMR-based metabolomics and machine learning.NPJ precision oncology · 2026Article
- Mechanisms of Mechanical Stress-Induced Vascular Remodeling via the Lactate-PKM2 Axis and Implications for Microgravity Adaptation.International journal of molecular sciences · 2026Article
- Review
- Profiling Protein Citrullination in Extracellular Vesicles by Single-Molecule Detection Using Direct Stochastic Optical Reconstruction Microscopy.Journal of biophotonics · 2026Article
- The moonlighting functions of glycolytic enzymes in tumorigenesis.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Metabolic reprogramming as a driver of immune escape in melanoma: implications for immunotherapy.Frontiers in immunology · 2026Review
- Roles of peptidylarginine deiminase (PAD) and protein citrullination in viral infections.Frontiers in microbiology · 2026Review
- Glycolytic reprogramming in cancer: immune crosstalk, nutrient competition, and supportive care perspectives.Frontiers in immunology · 2026Review
- Interaction of lncRNA LENT with DHX36 regulates translation and suppresses autophagy in melanoma.Cell death & disease · 2025Article
- Nuclear PKM2: a signal receiver, a gene programmer, and a metabolic modulator.Journal of biomedical science · 2025Review
- Prognostic value of circadian rhythm-associated genes in breast cancer.World journal of surgical oncology · 2025Article
- Lactic acid metabolism: gynecological cancer's Achilles' heel.Discover oncology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chromodomain helicase DNA binding protein 4 (CHD4) is an ATPase subunit of the Nucleosome Remodelling and Deacetylation (NuRD) complex that regulates gene expression. CHD4 is essential for growth of multiple patient derived melanoma xenografts and for breast cancer. Here we show that CHD4 regulates expression of PADI1 (Protein Arginine Deiminase 1) and PADI3 in multiple cancer cell types modulating citrullination of arginine residues of the allosterically-regulated glycolytic enzyme pyruvate kinase M2 (PKM2). Citrullination of PKM2 R106 reprogrammes cross-talk between PKM2 ligands lowering its sensitivity to the inhibitors Tryptophan, Alanine and Phenylalanine and promoting activation by Serine. Citrullination thus bypasses normal physiological regulation by low Serine levels to promote excessive glycolysis and reduced cell proliferation. We further show that PADI1 and PADI3 expression is up-regulated by hypoxia where PKM2 citrullination contributes to increased glycolysis. We provide insight as to how conversion of arginines to citrulline impacts key interactions within PKM2 that act in concert to reprogramme its activity as an additional mechanism regulating this important enzyme.
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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.