ArticleThe Journal of biological chemistry2009
Nuclear targeting of 6-phosphofructo-2-kinase (PFKFB3) increases proliferation via cyclin-dependent kinases.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers.
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Who cites it
138 citing papers in PubMed, 240 citations in OpenAlex.
- Trial
- Targeting PFKFB3 to enhance CDK4/6 inhibitor response in ER+ breast cancer.Breast cancer research : BCR · 2026Article
- Multi-omic identification of key transcriptional regulatory programs during endurance exercise training in rats.Nature communications · 2026Article
- Fructose-2,6-bisphosphate restores TDP-43 pathology-driven genome repair deficiency in motor neuron diseases.Communications biology · 2026Article
- USP7 facilitates brain tumor survival upon glucose deprivation by regulating phosphofructokinase muscle-type nuclear translocation in mice.PLoS biology · 2026Article
- Targeting aerobic glycolysis combats tyrosine kinase inhibitor resistance of hepatocellular carcinoma.International journal of cancer · 2026Review
- Glucose Metabolic Enzyme PFKFB3 in Cardiopulmonary Vascular Health and Disease.Circulation research · 2026Review
- NAT10 promotes the glycolysis of retinoblastoma through ac4C modification of PFKFB3 mRNA.BMC cancer · 2026Article
- Epigenetic reprogramming of hexokinase domain containing 1 (HKDC1) promotes proliferation in colorectal cancer.American journal of cancer research · 2026Article
- The glycolytic enzyme PFKFB3 alleviates DNA damage and chondrocyte senescence in osteoarthritis.Cell death discovery · 2025Article
- A noncanonical role of glycolytic metabolites controlling the timing of mouse embryo segmentation.Science advances · 2025Article
- Glycolytic flux controls retinal progenitor cell differentiation via regulating Wnt signaling.eLife · 2025Article
- PFKFB3 Connects Glycolytic Metabolism with Endothelial Dysfunction in Human and Rodent Obesity.Antioxidants (Basel, Switzerland) · 2025Article
- Metabolic adaptation to acute metabolic stress via PFKFB3 upregulation in rodent beta cells.Frontiers in endocrinology · 2025Article
- Stc2a inhibits IGF-stimulated somatic growth in favor of organismal survival under hypoxic stress.Frontiers in endocrinology · 2025Article
- The role of glycolysis in tumorigenesis: From biological aspects to therapeutic opportunities.Neoplasia (New York, N.Y.) · 2024Review
- Fructose-2,6-bisphosphate restores DNA repair activity of PNKP and ameliorates neurodegenerative symptoms in Huntington's disease.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Novel Candidate Genes Involved in an Initial Stage of White Striping Development in Broiler Chickens.Animals : an open access journal from MDPI · 2024Article
- Glycolytic PFKFB3 and Glycogenic UGP2 Axis Regulates Perfusion Recovery in Experimental Hind Limb Ischemia.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Fructose-2,6-bisphosphate restores DNA repair activity of PNKP and ameliorates neurodegenerative symptoms in Huntington's disease.bioRxiv : the preprint server for biology · 2024Article
78 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 1 institution in 2 countries.
Funding
Abstract
The regulation of metabolism and growth must be tightly coupled to guarantee the efficient use of energy and anabolic substrates throughout the cell cycle. Fructose 2,6-bisphosphate (Fru-2,6-BP) is an allosteric activator of 6-phosphofructo-1-kinase (PFK-1), a rate-limiting enzyme and essential control point in glycolysis. The concentration of Fru-2,6-BP in mammalian cells is set by four 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases (PFKFB1-4), which interconvert fructose 6-phosphate and Fru-2,6-BP. The relative functions of the PFKFB3 and PFKFB4 enzymes are of particular interest because they are activated in human cancers and increased by mitogens and low oxygen. We examined the cellular localization of PFKFB3 and PFKFB4 and unexpectedly found that whereas PFKFB4 localized to the cytoplasm (i.e. the site of glycolysis), PFKFB3 localized to the nucleus. We then overexpressed PFKFB3 and observed no change in glucose metabolism but rather a marked increase in cell proliferation. These effects on proliferation were completely abrogated by mutating either the active site or nuclear localization residues of PFKFB3, demonstrating a requirement for nuclear delivery of Fru-2,6-BP. Using protein array analyses, we then found that ectopic expression of PFKFB3 increased the expression of several key cell cycle proteins, including cyclin-dependent kinase (Cdk)-1, Cdc25C, and cyclin D3 and decreased the expression of the cell cycle inhibitor p27, a universal inhibitor of Cdk-1 and the cell cycle. We also observed that the addition of Fru-2,6-BP to HeLa cell lysates increased the phosphorylation of the Cdk-specific Thr-187 site of p27. Taken together, these observations demonstrate an unexpected role for PFKFB3 in nuclear signaling and indicate that Fru-2,6-BP may couple the activation of glucose metabolism with cell proliferation.
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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.