Affinage

PFKL

ATP-dependent 6-phosphofructokinase, liver type · UniProt P17858

Round 2 corrected
Length
780 aa
Mass
85.0 kDa
Annotated
2026-04-28
62 papers in source corpus 21 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PFKL is the liver-type subunit of phosphofructokinase-1, the rate-limiting enzyme of glycolysis, whose activity is tuned by an extensive network of allosteric, post-translational, and transcriptional controls that couple glucose flux to cellular state. Allosteric activation at the AMP/ADP effector site (targeted by small-molecule NA-11) diverts glucose from the pentose phosphate pathway, suppressing NADPH-dependent NOX2 oxidative burst and NETosis in neutrophils, while inhibitory inputs include O-GlcNAcylation at S529 (redirecting flux to the PPP under hypoxia), PRMT9-mediated methylation at R301, and local PGE2 production by PTGES3 (PMID:34320407, PMID:22923583, PMID:40222696, PMID:37831605). Protein stability is governed by ubiquitin-dependent degradation through E3 ligases A20 and PDLIM2 and counteracted by deubiquitinases USP39 and USP14, while HDAC6-mediated deacetylation at K563 promotes active tetramer assembly and phosphorylation at S775 during innate immune signaling increases catalytic output (PMID:32015333, PMID:36276075, PMID:41421488, PMID:39085210). Beyond canonical glycolysis, under energy stress PFKL translocates to lipid droplets and functions as a protein kinase that phosphorylates PLIN2, tethering lipid droplets to mitochondria to enable β-oxidation (PMID:38773347).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1981 High

    Mapping PFKL to chromosome 21 and demonstrating gene-dosage effects in trisomy 21 established that liver-type PFK subunit copy number directly determines isozyme composition and total PFK activity in human erythrocytes.

    Evidence Somatic cell hybrid panel with subunit-specific monoclonal antibody; chromatographic isozyme profiling of trisomy 21 erythrocytes

    PMID:6455664

    Open questions at the time
    • Mechanism by which excess PFKL alters erythrocyte metabolism in Down syndrome remains uncharacterized
    • No structure–function information at this stage
  2. 1998 Medium

    Transgenic PFKL-overexpressing mice revealed that gene-dosage-driven increases in PFK activity are tissue- and age-dependent and directly accelerate cerebral glucose utilization, connecting enzyme level to whole-organ metabolic flux.

    Evidence Transgenic mice with PFKL overexpression; in vivo ¹³C-NMR brain metabolic flux; tissue PFK activity assays

    PMID:8172601 PMID:9813288

    Open questions at the time
    • Whether the metabolic shift contributes to neurodevelopmental phenotypes was not tested
    • Activity regulation beyond gene dosage not addressed
  3. 2012 High

    Identification of O-GlcNAcylation at S529 as an inhibitory post-translational modification revealed the first site-specific mechanism through which PFKL activity is suppressed to redirect glucose into the pentose phosphate pathway under hypoxia, conferring a cancer cell growth advantage.

    Evidence In vitro PFK1 activity assays with S529A mutagenesis; metabolic flux analysis; xenograft tumor models

    PMID:22923583

    Open questions at the time
    • Identity of the O-GlcNAc transferase and phosphatase controlling S529 occupancy not defined
    • Relative contribution of PFKL vs. PFKM/PFKP O-GlcNAcylation in vivo unclear
  4. 2021 High

    Structural and pharmacological characterization of PFKL's allosteric activation site by NA-11 resolved how small-molecule occupancy of the AMP/ADP pocket locks the enzyme in the active R-state and explained isoform selectivity, while showing that PFKL activation diverts neutrophil glucose away from the PPP to suppress NOX2-dependent oxidative burst and NETosis.

    Evidence High-resolution crystal structure of PFKL–NA-11 complex; chemical proteomics with two probes; neutrophil ROS/NETosis assays; glycolysis flux measurements

    PMID:34320407

    Open questions at the time
    • In vivo efficacy and pharmacokinetics of NA-11 class activators not fully characterized
    • Structural basis for negative allosteric regulation (e.g., citrate, PGE2) unresolved
  5. 2022 Medium

    Multiple studies converged to show that PFKL protein stability is controlled by ubiquitin-dependent degradation — E3 ligases A20 and PDLIM2 promote PFKL turnover, while deubiquitinases USP39 (recruited via DNAAF5) and later USP14 oppose degradation — establishing regulated proteolysis as a major layer of glycolytic control in cancer.

    Evidence Co-IP plus ubiquitination/deubiquitination assays in HCC, laryngeal SCC, and OSCC cells; xenograft models; DNAAF5-KO epistasis

    PMID:32015333 PMID:35723199 PMID:36276075 PMID:38388430

    Open questions at the time
    • Ubiquitination site(s) on PFKL not mapped
    • Whether A20, PDLIM2, USP39, and USP14 act on the same or distinct ubiquitin chains is unknown
    • SQSTM1-mediated lysosomal degradation (via Cav1 competition) adds complexity not yet integrated
  6. 2023 High

    PFKL was placed under direct transcriptional control of KLF7 (activating) and EGR1 (repressing), linking PFKL expression to cardiac metabolic remodeling and hepatocellular carcinoma, and demonstrating that PFKL levels are rate-limiting for pathological glycolysis in these contexts.

    Evidence Cardiac-specific KLF7 KO/OE mice with PFKL-knockdown rescue; ChIP at PFKL promoter for KLF7 and EGR1; HCC xenograft and organoid models

    PMID:36810848 PMID:38287371

    Open questions at the time
    • Additional transcription factors controlling PFKL in other tissues not mapped
    • Integration of transcriptional and post-translational regulation quantitatively undefined
  7. 2023 High

    Discovery that PTGES3 binds PFKL and generates local PGE2 to allosterically inhibit enzyme activity revealed a lipid-metabolite-mediated regulatory axis restraining glycolysis and invasion in ovarian cancer cells.

    Evidence Genome-wide CRISPR invasion screen; Co-IP; direct enzymatic activity assays with PTGES3 KO/OE

    PMID:37831605

    Open questions at the time
    • PGE2 binding site on PFKL not structurally defined
    • Whether this mechanism operates outside ovarian cancer is untested
  8. 2024 High

    Phosphorylation of PFKL at S775 during innate immune activation was shown to directly increase catalytic activity and glycolytic flux in macrophages; knock-in S775A mice exhibited blunted HIF1α/IL-1β responses, placing PFKL phosphorylation as a metabolic checkpoint in inflammation.

    Evidence Biochemical activity assays; PfklS775A knock-in mouse; in vivo LPS inflammation model

    PMID:39085210

    Open questions at the time
    • Kinase responsible for S775 phosphorylation not identified
    • Whether S775 phosphorylation occurs in non-myeloid immune cells is unknown
  9. 2024 High

    The discovery that PFKL translocates to lipid droplets under energy stress and functions as a protein kinase phosphorylating PLIN2 to tether lipid droplets to mitochondria fundamentally expanded PFKL's role beyond glycolysis into lipid catabolism and organelle communication.

    Evidence In vitro kinase assay (PFKL → PLIN2); lipid droplet isolation; proximity ligation assay for LD–mitochondria contacts; mouse liver tumor models

    PMID:38773347

    Open questions at the time
    • Structural basis for PFKL protein kinase activity and its relationship to the metabolite kinase domain unknown
    • Full substrate repertoire of PFKL as a protein kinase not surveyed
    • Signal triggering PFKL translocation to lipid droplets not molecularly defined
  10. 2025 High

    Identification of HDAC6-mediated deacetylation at K563 as a driver of active tetramer assembly, and PRMT9-mediated methylation at R301 as an inactivating modification, added two new post-translational switches that tune PFKL quaternary structure and activity in vascular smooth muscle cells and neutrophils, respectively.

    Evidence Co-IP; HDAC6 inhibitor/siRNA; K563R/K563Q mutagenesis with in vivo neointimal formation model; mass spectrometry methylation site ID; PDK4-KO mouse model for lactate/PRMT9 axis

    PMID:40222696 PMID:41421488

    Open questions at the time
    • Interplay among S529 O-GlcNAcylation, K563 acetylation, R301 methylation, and S775 phosphorylation on the same PFKL molecule not examined
    • Whether HDAC6–PFKL interaction is direct or scaffold-mediated is unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis for PFKL's protein kinase activity toward PLIN2, the identity of the S775 kinase, how multiple PTMs are integrated on a single tetramer, and whether allosteric activators can be therapeutically deployed in inflammatory disease.
  • No structural model of PFKL protein kinase activity exists
  • Kinase for S775 unidentified
  • Quantitative integration of combinatorial PTMs on PFKL not modeled
  • In vivo therapeutic window for PFKL allosteric activators not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 3 GO:0098772 molecular function regulator activity 3 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005829 cytosol 2 GO:0005811 lipid droplet 1
Pathway
R-HSA-1430728 Metabolism 6 R-HSA-1643685 Disease 6 R-HSA-168256 Immune System 3
Partners
A20DNAAF5HDAC6PDLIM2PLIN2PTGES3USP14USP39

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1981 PFKL (liver-type phosphofructokinase subunit) was mapped to human chromosome 21 using somatic cell hybrids and a subunit-specific monoclonal antibody. Trisomy 21 individuals showed elevated erythrocyte PFK activity due to a gene-dosage effect, with a striking increase in L4 homotetrameric species. Somatic cell hybrid panel analysis with monoclonal antibody immunoprecipitation; chromatographic isozyme analysis of trisomy 21 erythrocytes Proceedings of the National Academy of Sciences of the United States of America High 6455664
1994 Transgenic mice overexpressing PFKL showed tissue-specific overexpression resembling endogenous enzyme distribution. PFKL overexpression nearly doubled PFK activity in embryonic brain but not adult brain, indicating temporally regulated gene-dosage effects relevant to Down syndrome pathology. Transgenic mouse construction with murine PFKL gene-cDNA hybrid; tissue PFK activity assays The Biochemical journal Medium 8172601
1998 Transgenic-PFKL mice with elevated PFKL activity exhibited slower blood glucose clearance but a 58% faster rate of cerebral glucose utilization compared to controls, demonstrating that PFKL overexpression directly alters brain glucose metabolism in vivo. In vivo [1-13C]-glucose infusion with NMR brain metabolic rate measurements in transgenic vs. non-transgenic mice Brain research Medium 9813288
2012 O-GlcNAcylation of phosphofructokinase 1 (PFK1) at serine 529 inhibits its enzymatic activity and redirects glucose flux from glycolysis to the pentose phosphate pathway under hypoxia, conferring a selective growth advantage to cancer cells. Blocking glycosylation at S529 reduced cancer cell proliferation and impaired tumor formation. In vitro PFK1 activity assays with O-GlcNAc site-specific mutagenesis (S529A); metabolic flux analysis; xenograft tumor models Science High 22923583
2020 The E3 ubiquitin ligase A20 interacts with PFKL and promotes its ubiquitin-mediated proteasomal degradation, thereby inhibiting glycolysis in hepatocellular carcinoma cells. Downregulation of A20 in HCC leads to PFKL accumulation and enhanced glycolysis, proliferation, and migration. Co-immunoprecipitation; RNA interference; glycolysis assays; HCC cell line functional studies Cell death & disease Medium 32015333
2021 Small-molecule NA-11 (analog of LDC7559) selectively activates PFKL by binding to the AMP/ADP allosteric activation site, increasing glycolytic flux and thereby dampening flux through the pentose phosphate pathway. This reduces NADPH availability for NOX2, suppressing the oxidative burst, NETosis, and tissue damage in neutrophils. High-resolution crystal structure of PFKL confirmed the NA-11 binding site and explained isoform selectivity over PFKP and PFKM. Chemical proteomics (two unbiased strategies); high-resolution crystal structure of PFKL–NA-11 complex; neutrophil ROS/NETosis assays; glycolysis flux measurements Cell High 34320407
2021 PFKL is a direct molecular target of penfluridol; direct binding of penfluridol to PFKL inhibits its glycolytic activity, leading to AMPK activation, nuclear translocation of FOXO3a, and BIM-dependent apoptosis in esophageal squamous cell carcinoma cells. PFKL-deficient cells are insensitive to penfluridol, confirming PFKL as the essential target. DARTS (drug affinity responsive target stability) technology; proteomics; AMPK/FOXO3a pathway analysis; PFKL knockdown rescue experiments Acta pharmaceutica Sinica. B Medium 35530161
2022 YTHDF3 promotes PFKL expression by suppressing PFKL mRNA degradation via m6A modification. In turn, PFKL positively regulates YTHDF3 protein stability by interacting with EFTUD2 (a spliceosome subunit), which inhibits ubiquitination of YTHDF3, forming a positive regulatory feedback loop. MeRIP (methylated RNA immunoprecipitation); Co-immunoprecipitation; ubiquitination assays; loss/gain-of-function in HCC cell lines and in vivo Journal of experimental & clinical cancer research Medium 36471428
2022 PDLIM2, an E3 ubiquitin ligase, promotes ubiquitination and degradation of PFKL in laryngeal squamous cell carcinoma cells, thereby restraining glycolysis. M2 macrophage-derived exosomes deliver miR-222-3p to suppress PDLIM2, leading to PFKL stabilization and enhanced glycolysis. Co-immunoprecipitation; ubiquitination assay; luciferase reporter (miR-222-3p/PDLIM2); Seahorse ECAR/OCR; xenograft mouse model Neoplasma Medium 35723199
2022 DNAAF5 directly binds PFKL and recruits the deubiquitinase USP39 to form a ternary complex, promoting PFKL deubiquitination and protein stabilization, thereby enhancing glycolysis and HCC cell proliferation. Transcriptome sequencing; mass spectrometry; Co-immunoprecipitation; ubiquitination assays; DNAAF5 KO and OE cell lines; xenograft mouse model Frontiers in oncology Medium 36276075
2022 PFKL preferentially interacts with oxidized methionine-containing actin peptides (Met44/Met47 oxidized) compared to the reduced form, and this differential interaction also occurs with full-length actin protein, suggesting that methionine oxidation on actin modulates the actin–PFKL interaction under oxidative stress conditions. Photo-crosslinking peptide approach; quantitative proteomics; validation with full-length actin protein RSC chemical biology Medium 36320891
2023 KLF7 transcriptionally activates PFKL (the rate-limiting glycolytic enzyme) and ACADL (long-chain acyl-CoA dehydrogenase, key for fatty acid oxidation) simultaneously. Cardiac-specific KLF7 knockout caused adult concentric hypertrophy by shifting metabolism toward glycolysis; overexpression caused infant eccentric hypertrophy. Knockdown of PFKL or overexpression of ACADL partially rescued hypertrophy in KLF7-deficient mice. Cardiac-specific KO and OE transgenic mice; genetic epistasis (PFKL knockdown rescue); ChIP for KLF7 at PFKL/ACADL promoters; metabolic flux assays Nature communications High 36810848
2023 PTGES3 binds directly to PFKL and generates a local source of prostaglandin E2 (PGE2) that allosterically inhibits PFKL enzymatic activity, suppressing glycolysis and the TCA cycle, and restraining ovarian cancer cell invasiveness. Loss of PTGES3 in ovarian cancer disrupts this inhibitory axis, hyperactivating glucose oxidation. Genome-wide CRISPR-Cas9 invasion screen; Co-immunoprecipitation; enzymatic activity assays; PTGES3 KO/OE functional assays Cell reports High 37831605
2023 Caveolin-1 (Cav1) competes with SQSTM1 for binding to the regulatory subunit of PFKL in hepatic stellate cells, thereby inhibiting SQSTM1-mediated autophagy-independent lysosomal degradation of PFKL and sustaining its protein levels to maintain HSC activation and glycolysis during liver fibrosis. HSC-specific Cav1 knockdown mouse model; Co-immunoprecipitation; lysosomal degradation pathway assays; primary mouse HSC activation studies Free radical biology & medicine Medium 37116593
2024 PFKL is phosphorylated at Ser775 in macrophages following innate immune stimulation (e.g., LPS). This phosphorylation increases PFKL catalytic activity and glycolytic flux. Knock-in mice carrying the phosphorylation-defective S775A mutation show reduced glycolysis, lower HIF1α and IL-1β levels upon LPS stimulation, and attenuated inflammatory cytokines (MCP-1, IL-1β) in vivo. Biochemical activity assays; phosphorylation-defective PFKL knock-in mouse model (PfklS775A/S775A); glycolysis monitoring; in vivo inflammation model Nature communications High 39085210
2024 EGR1 transcriptionally represses PFKL by interacting with the PFKL promoter region, reducing PFKL-mediated aerobic glycolysis in HCC. EGR1 overexpression inhibits HCC proliferation in a PFKL-dependent manner. ChIP/promoter-binding assay; EGR1 OE/KD in HCC cell lines and xenograft models; human organoid HCC model; glycolysis assays Journal of experimental & clinical cancer research Medium 38287371
2024 Under glucose deprivation, PFKL is phosphorylated (reducing glycolytic activity) and translocates to lipid droplets, where it acts as a protein kinase that phosphorylates PLIN2. Phospho-PLIN2 recruits CPT1A, tethering lipid droplets to mitochondria and enabling adipose triglyceride lipase (ATGL) recruitment for lipolysis and β-oxidation. Disruption of this cascade inhibits tumor cell proliferation and blunts liver tumor growth. In vitro kinase assay (PFKL phosphorylating PLIN2); Co-IP; subcellular fractionation/lipid droplet isolation; proximity ligation assay for LD-mitochondria tethering; mouse liver tumor models Nature metabolism High 38773347
2024 USP14 is a deubiquitinating enzyme for PFKL; USP14 interacts with PFKL and stabilizes it through deubiquitination in oral squamous cell carcinoma cells, enhancing glycolytic flux and promoting proliferation, migration, and tumorigenesis. Co-immunoprecipitation; deubiquitination assay; USP14 KD/OE functional studies in OSCC cells; xenograft model Journal of translational medicine Medium 38388430
2025 HDAC6 acts as a deacetylase for PFKL, interacting with PFKL to remove acetylation and enhance its activity by accelerating PFKL tetrameric assembly and aerobic glycolysis, thereby promoting vascular smooth muscle cell (VSMC) proliferation. The primary acetylation site was identified as K563; the K563R (deacetylation-mimetic) mutant aggravated VSMC proliferation and neointimal formation, while K563Q (acetylation-mimetic) attenuated it. Co-immunoprecipitation; HDAC6 siRNA/inhibitor (TSA); site-directed mutagenesis (K563R, K563Q); recombinant adenoviral expression; ligation-induced neointimal formation in vivo The Journal of biological chemistry High 41421488
2025 PRMT9-mediated methylation of PFKL at R301 inactivates PFKL, restricting glycolysis and redirecting metabolic flux toward the pentose phosphate pathway in neutrophils. This occurs in the context of lactate signaling from cardiomyocytes and drives NETosis in diabetic myocardial infarction. Mass spectrometry imaging; in vivo/in vitro lactate supplementation/depletion; PFKL methylation site identification; PDK4 cardiomyocyte-specific KO mouse model Pharmacological research Medium 40222696
2025 A covalent PFKL activator (electrophile-drug conjugate, EDC) site-specifically modifies K677 in the allosteric effector site of PFKL, stabilizing the active R-state tetramer and inducing metabolic imbalance in cancer cells. This EDC selectively modifies PFKL proteome-wide and suppresses tumor growth in vitro and in vivo. Chemical proteomics (proteome-wide selectivity); site-directed covalent modification; biochemical PFKL activity assays; in vitro and in vivo tumor growth assays bioRxivpreprint Medium 41256653

Source papers

Stage 0 corpus · 62 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Towards a proteome-scale map of the human protein-protein interaction network. Nature 2090 16189514
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2010 Network organization of the human autophagy system. Nature 1286 20562859
2009 Defining the human deubiquitinating enzyme interaction landscape. Cell 1282 19615732
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2004 Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. Nature biotechnology 916 15592455
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2000 The DNA sequence of human chromosome 21. Nature 808 10830953
2008 Global analysis of host-pathogen interactions that regulate early-stage HIV-1 replication. Cell 787 18854154
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2006 A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration. Cell 610 16713569
2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
2012 Phosphofructokinase 1 glycosylation regulates cell growth and metabolism. Science (New York, N.Y.) 528 22923583
2003 Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nature biotechnology 485 12665801
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
2011 Defining human ERAD networks through an integrative mapping strategy. Nature cell biology 427 22119785
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2007 Systematic analysis of the protein interaction network for the human transcription machinery reveals the identity of the 7SK capping enzyme. Molecular cell 367 17643375
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2017 Genome-wide CRISPR screen identifies HNRNPL as a prostate cancer dependency regulating RNA splicing. Proceedings of the National Academy of Sciences of the United States of America 282 28611215
2012 A high-throughput approach for measuring temporal changes in the interactome. Nature methods 273 22863883
2004 Functional proteomics mapping of a human signaling pathway. Genome research 247 15231748
2009 Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT). Journal of proteome research 237 19199708
2021 Selective activation of PFKL suppresses the phagocytic oxidative burst. Cell 122 34320407
2024 Glycolytic enzyme PFKL governs lipolysis by promoting lipid droplet-mitochondria tethering to enhance β-oxidation and tumor cell proliferation. Nature metabolism 98 38773347
1981 Assignment of the human gene for liver-type 6-phosphofructokinase isozyme (PFKL) to chromosome 21 by using somatic cell hybrids and monoclonal anti-L antibody. Proceedings of the National Academy of Sciences of the United States of America 89 6455664
2020 A20 targets PFKL and glycolysis to inhibit the progression of hepatocellular carcinoma. Cell death & disease 87 32015333
2021 Targeting PFKL with penfluridol inhibits glycolysis and suppresses esophageal cancer tumorigenesis in an AMPK/FOXO3a/BIM-dependent manner. Acta pharmaceutica Sinica. B 81 35530161
2022 A functional loop between YTH domain family protein YTHDF3 mediated m6A modification and phosphofructokinase PFKL in glycolysis of hepatocellular carcinoma. Journal of experimental & clinical cancer research : CR 56 36471428
2024 EGR1 suppresses HCC growth and aerobic glycolysis by transcriptionally downregulating PFKL. Journal of experimental & clinical cancer research : CR 41 38287371
2023 The KLF7/PFKL/ACADL axis modulates cardiac metabolic remodelling during cardiac hypertrophy in male mice. Nature communications 38 36810848
2019 125I suppressed the Warburg effect viaregulating miR-338/PFKL axis in hepatocellular carcinoma. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 37 31514072
1994 Overexpression of liver-type phosphofructokinase (PFKL) in transgenic-PFKL mice: implication for gene dosage in trisomy 21. The Biochemical journal 25 8172601
2024 Phosphorylation of PFKL regulates metabolic reprogramming in macrophages following pattern recognition receptor activation. Nature communications 23 39085210
1998 Altered brain glucose metabolism in transgenic-PFKL mice with elevated L-phosphofructokinase: in vivo NMR studies. Brain research 18 9813288
2022 Exosomes from M2 macrophages promoted glycolysis in FaDu cells by inhibiting PDLIM2 expression to stabilize PFKL. Neoplasma 17 35723199
2023 Allosterically inhibited PFKL via prostaglandin E2 withholds glucose metabolism and ovarian cancer invasiveness. Cell reports 16 37831605
2022 DNAAF5 promotes hepatocellular carcinoma malignant progression by recruiting USP39 to improve PFKL protein stability. Frontiers in oncology 16 36276075
2021 Inhibition of miR-185-3p Confers Erlotinib Resistance Through Upregulation of PFKL/MET in Lung Cancers. Frontiers in cell and developmental biology 14 34368128
2024 Ubiquitin-specific protease 14 targets PFKL-mediated glycolysis to promote the proliferation and migration of oral squamous cell carcinoma. Journal of translational medicine 13 38388430
2023 Caveolin-1 depletion attenuates hepatic fibrosis via promoting SQSTM1-mediated PFKL degradation in HSCs. Free radical biology & medicine 13 37116593
2021 Antitumor effects of the small molecule DMAMCL in neuroblastoma via suppressing aerobic glycolysis and targeting PFKL. Cancer cell international 13 34819091
2022 miR-21-5p/Tiam1-mediated glycolysis reprogramming drives breast cancer progression via enhancing PFKL stabilization. Carcinogenesis 12 35511493
2024 EIF4A3-Induced CircDHTKD1 regulates glycolysis in non-small cell lung cancer via stabilizing PFKL. Journal of cellular and molecular medicine 11 39022816
2022 ApoM regulates PFKL through the transcription factor SREBF1 to inhibit the proliferation, migration and metastasis of liver cancer cells. Oncology letters 11 35720503
2021 Bta-miR-6517 promotes proliferation and inhibits differentiation of pre-adipocytes by targeting PFKL. Journal of animal physiology and animal nutrition 8 34791721
1988 A DNA polymorphism with KpnI of the human liver-type phosphofructokinase (PFKL) gene. Nucleic acids research 7 2902561
2025 Cardiac PDK4 promotes neutrophilic PFKL methylation and drives the innate immune response in diabetic myocardial infarction. Pharmacological research 5 40222696
2022 PFKL, a novel regulatory node for NOX2-dependent oxidative burst and NETosis. Journal of Zhejiang University. Science. B 4 35794690
2024 PFKL promotes cell viability and glycolysis and inhibits cisplatin chemosensitivity of laryngeal squamous cell carcinoma. Biochemical and biophysical research communications 2 38991254
2025 piR-hsa-35410 promotes triple-negative breast cancer progression via enhancing PFKL mediated glycolysis. Biochemical pharmacology 0 40953645
2025 Hypoxia-Induced m6A modification via YTHDF2 stabilizes PFKL to fuel MDSC Glycolysis and hepatocellular carcinoma progression. Functional & integrative genomics 0 41225244
2025 A Covalent PFKL Activator Suppresses Tumor Growth. bioRxiv : the preprint server for biology 0 41256653
2025 HDAC6-mediated PFKL deacetylation enhances aerobic glycolysis and promotes VSMC proliferation. The Journal of biological chemistry 0 41421488
2022 A peptide-crosslinking approach identifies HSPA8 and PFKL as selective interactors of an actin-derived peptide containing reduced and oxidized methionine. RSC chemical biology 0 36320891