ArticleCell death & disease2021
SUMOylation disassembles the tetrameric pyruvate kinase M2 to block myeloid differentiation of leukemia cells.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 32 citations in OpenAlex.
- Unveiling lactylation: A novel frontier in the pathogenesis of diabetic nephropathy (Review).International journal of molecular medicine · 2026Review
- Upregulation of GnT-IVa and Its Critical Roles in ATRA-Induced Differentiation of Acute Promyelocytic Leukemia Cells.Biomolecules · 2026Article
- Mechanisms of Mechanical Stress-Induced Vascular Remodeling via the Lactate-PKM2 Axis and Implications for Microgravity Adaptation.International journal of molecular sciences · 2026Article
- Glycolysis and glycolytic enzymes in acute myeloid leukemia: Warburg and beyond.Frontiers in pharmacology · 2026Review
- Article
- Metabolomic Investigation of Myelodysplastic Syndromes, Multiple Myeloma, and Homozygous β-Thalassemia.Cells · 2025Review
- Pyruvate Kinase M2 Links Metabolism and Epigenetics: A New Target for Liver Disease Treatment.Biomolecules · 2025Review
- Nuclear PKM2: a signal receiver, a gene programmer, and a metabolic modulator.Journal of biomedical science · 2025Review
- Review
- Metabolic dysregulation in myelodysplastic neoplasm: impact on pathogenesis and potential therapeutic targets.Medical oncology (Northwood, London, England) · 2024Review
- CHAC1 blockade suppresses progression of lung adenocarcinoma by interfering with glucose metabolism via hijacking PKM2 nuclear translocation.Cell death & disease · 2024Article
- The role of PKM2 in cancer progression and its structural and biological basis.Journal of physiology and biochemistry · 2024Review
- Distinctive tumorigenic significance and innovative oncology targets of SUMOylation.Theranostics · 2024Review
- Targeting pyruvate kinase M2 for the treatment of kidney disease.Frontiers in pharmacology · 2024Review
- Pyruvate kinase is post-translationally regulated by sirtuin 2 in Aedes aegypti mosquitoes.Insect biochemistry and molecular biology · 2023Article
- Review
- The Role of Reprogrammed Glucose Metabolism in Cancer.Metabolites · 2023Review
- The BCAT1 CXXC Motif Provides Protection against ROS in Acute Myeloid Leukaemia Cells.Antioxidants (Basel, Switzerland) · 2022Article
- Regulation of Glucose, Fatty Acid and Amino Acid Metabolism by Ubiquitination and SUMOylation for Cancer Progression.Frontiers in cell and developmental biology · 2022Review
- Lactylation of PKM2 Suppresses Inflammatory Metabolic Adaptation in Pro-inflammatory Macrophages.International journal of biological sciences · 2022Article
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 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Leukemia arises from blockage of the differentiation/maturation of hematopoietic progenitor cells at different stages with uncontrolled proliferation of leukemic cells. However, the signal pathways that block cell differentiation remain unclear. Herein we found that SUMOylation of the M2 isoform of pyruvate kinase (PKM2), a rate-limiting glycolytic enzyme catalyzing the dephosphorylation of phosphoenolpyruvate to pyruvate, is prevalent in a variety of leukemic cell lines as well as primary samples from patients with leukemia through multiple-reaction monitoring based targeted mass spectrometry analysis. SUMOylation of PKM2 lysine 270 (K270) triggered conformation change from tetrameric to dimeric of PKM2, reduced PK activity, and led to nuclear translocation of PKM2. SUMO1 modification of PKM2 recruits and promotes degradation of RUNX1 via a SUMO-interacting motif, resulting in blockage of myeloid differentiation of NB4 and U937 leukemia cells. Replacement of wild type PKM2 with a SUMOylation-deficient mutant (K270R) abrogated the interaction with RUNX1, and the blockage of myeloid differentiation in vitro and in xenograft model. Our results establish PKM2 as an essential modulator of leukemia cell differentiation and a potential therapeutic target, which may offer synergistic effect with differentiation therapy in the treatment of leukemia.
Indexed as
Identifiers
What OpenQuestion holds
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.