Affinage

PFKP

ATP-dependent 6-phosphofructokinase, platelet type · UniProt Q01813

Length
784 aa
Mass
85.6 kDa
Annotated
2026-04-28
56 papers in source corpus 33 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PFKP encodes the platelet/fibroblast isoform of phosphofructokinase-1, the rate-limiting glycolytic enzyme that converts fructose-6-phosphate to fructose-1,6-bisphosphate, and serves as a central node integrating metabolic flux with signal transduction, autophagy, DNA repair, and cell fate decisions. Beyond its canonical glycolytic function, PFKP possesses non-canonical protein kinase activity, directly phosphorylating ATG4B at S34 to activate autophagic flux and Lin41 to stabilize it during endodermal specification (PMID:33607258, PMID:36660859). PFKP protein stability is tightly controlled by multiple E3 ubiquitin ligases (HRD1, TRIM25/CMBL, RNF123, TRIM21/PKP1) and counterbalanced by deubiquitinases (USP5, USP14), while its enzymatic activity is modulated by SIRT2-mediated deacetylation at K394/K395, lactylation at K688 and K392 with opposing effects, and O-GlcNAcylation (PMID:33588886, PMID:37967006, PMID:36865524, PMID:41919225). ATM-dependent phosphorylation at T278 converts PFKP tetramers to dimers that translocate to the nucleus via Cyclin D3/CDK6–importin 9, where dimeric PFKP recruits CK2 to phosphorylate RAD51 for homologous recombination repair and activates CXCR4 transcription through c-Myc (PMID:42011782, PMID:34255748).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1983 High

    Establishing the chromosomal identity of PFKP resolved which locus encodes the platelet/fibroblast PFK-1 isoform, enabling all subsequent isoform-specific studies.

    Evidence Somatic cell hybrid analysis with anti-P subunit antiserum and gene dosage experiments mapping PFKP to chromosome 10p

    PMID:6222962

    Open questions at the time
    • No coding sequence or protein structure determined at this stage
    • Regulatory elements uncharacterized
  2. 2011 High

    Identification of KLF4 as a direct transcriptional activator of PFKP established that PFKP expression is selectively regulated among PFK isoforms to control glycolytic flux in cancer.

    Evidence ChIP showing KLF4 binding to PFKP promoter, luciferase reporter, KD/OE with glycolysis readouts in breast cancer cells

    PMID:21586797

    Open questions at the time
    • Whether KLF4-PFKP axis operates in non-cancer contexts unknown
    • Other transcription factors not yet mapped
  3. 2017 High

    Demonstrating that Snail represses PFKP to reroute glucose from glycolysis to the pentose phosphate pathway revealed PFKP as a metabolic switch point during EMT.

    Evidence Snail KD/OE with metabolic flux measurements and PFKP rescue experiments plus in vivo metastasis assays

    PMID:28176759

    Open questions at the time
    • Mechanism of Snail-mediated PFKP repression (direct binding vs. indirect) not fully resolved
    • Contribution of other PFK isoforms during EMT unclear
  4. 2018 Medium

    Discovery that VDAC2 physically sequesters PFKP on the mitochondrial outer membrane to suppress glycolysis provided the first evidence of a mitochondrial interaction restraining PFKP activity.

    Evidence Co-IP of VDAC2-PFKP, VDAC2 KD/OE with glycolysis and stemness markers, clotrimazole rescue in glioma cells

    PMID:30250190

    Open questions at the time
    • Structural basis of VDAC2-PFKP interaction unknown
    • Not independently replicated outside glioma context
    • Whether VDAC2 regulation is isoform-specific for PFKP unclear
  5. 2021 High

    Multiple studies in 2021 collectively revealed that PFKP is a nucleocytoplasmic shuttling protein with non-canonical protein kinase activity, fundamentally expanding its role beyond glycolysis: Cyclin D3/CDK6 exposes an NLS to drive importin 9-dependent nuclear entry where PFKP activates CXCR4 via c-Myc; separately, PFKP directly phosphorylates ATG4B at S34 to promote autophagy.

    Evidence NLS/NES mutagenesis, Co-IP of CDK6-PFKP and PFKP-importin 9, CXCR4 reporter, in vivo leukemia model (PMID:34255748); in vitro kinase assay with phospho-site mutagenesis, CRISPR KO, LC3 turnover (PMID:33607258)

    PMID:33607258 PMID:34255748

    Open questions at the time
    • Kinase domain or catalytic residues responsible for PFKP's protein kinase activity not structurally defined
    • Full spectrum of PFKP kinase substrates unknown
    • Whether nuclear PFKP retains glycolytic activity unclear
  6. 2021 High

    Identification of HRD1 as an E3 ligase targeting PFKP for proteasomal degradation, together with the R-2HG/FTO/m6A epitranscriptomic axis controlling PFKP mRNA stability, established that PFKP abundance is tightly regulated at both protein and mRNA levels.

    Evidence MS interactome, Co-IP, ubiquitination assay for HRD1 (PMID:33588886); m6A-seq, FTO/YTHDF2 KD, mRNA decay assays in leukemia (PMID:33434505)

    PMID:33434505 PMID:33588886

    Open questions at the time
    • Interplay between transcriptional, epitranscriptomic, and ubiquitin-mediated regulation not integrated
    • Whether HRD1 targets PFKP from the ER membrane or in the cytosol not fully clarified
  7. 2021 High

    Mapping additional transcriptional inputs — YY1/BRD2/4 in prostate cancer and SMAD3-SP1 downstream of TGF-β1 in kidney fibrosis — demonstrated that PFKP transcription is controlled by context-specific transcription factor combinations.

    Evidence ChIP-seq and cis-element mutagenesis for YY1 (PMID:33849067); ChIP-qPCR for SMAD3-SP1 binding, AAV-mediated PFKP KD/OE in mice (PMID:38086793)

    PMID:33849067 PMID:38086793

    Open questions at the time
    • How multiple TFs are coordinated at the PFKP promoter in a single cell type is unknown
    • Epigenetic regulation of the PFKP locus beyond BRD2/4 not explored
  8. 2022 High

    The finding that PFKP physically interacts with AMPK and promotes mitochondrial AMPK-dependent fatty acid oxidation during glucose starvation revealed a metabolic adaptor function independent of PFK-1 catalytic activity.

    Evidence Proteomics screen, Co-IP, mitochondrial fractionation, ACC2 phosphorylation, FAO measurements in NSCLC cells

    PMID:35641476

    Open questions at the time
    • Whether PFKP's glycolytic versus AMPK-scaffolding functions are mutually exclusive not determined
    • PFKP domains mediating AMPK interaction not mapped
  9. 2022 High

    Fbxo7 was shown to coordinate CDK6-dependent phosphorylation and CDK6-independent ubiquitination of PFKP, providing an additional regulatory node linking cell cycle machinery to glycolytic control in T cells.

    Evidence Fbxo7 KO in CD4+ T cells, CDK6 activity assays, ubiquitination assay, metabolomics

    PMID:35670764

    Open questions at the time
    • Specific phosphorylation site(s) on PFKP targeted by CDK6 via Fbxo7 not mapped
    • Whether Fbxo7-mediated PFKP ubiquitination uses K48 or other linkage types not defined
  10. 2023 High

    SIRT2-mediated deacetylation at K394/K395 established that acetylation is an activating mark for PFKP enzymatic activity and its kinase activity toward ATG4B, linking metabolic regulation to LC3-associated phagocytosis in macrophages.

    Evidence SIRT2 inhibition, K394 mutagenesis, PFKP activity assays, ATG4B phosphorylation, LAP/phagocytosis assays, in vivo sepsis model

    PMID:36865524

    Open questions at the time
    • Acetyltransferase that deposits K394/K395 acetylation not identified
    • Whether deacetylation also affects PFKP's kinase activity toward Lin41 unknown
  11. 2023 High

    Discovery that p53 activates CMBL to enhance TRIM25-mediated K48 ubiquitination of PFKP connected genotoxic stress signaling to glycolytic suppression, adding TRIM25 to the growing list of PFKP E3 ligases.

    Evidence Co-IP of CMBL-TRIM25-PFKP ternary complex, ubiquitination assay, p53 activation, glycolysis measurements in colorectal cancer

    PMID:37967006

    Open questions at the time
    • Specific lysine(s) on PFKP targeted by TRIM25 not mapped
    • Whether CMBL adaptor function is specific to TRIM25 or generalizable to other E3s unknown
  12. 2023 High

    PFKP's non-canonical kinase activity was extended to a second substrate, Lin41, where phosphorylation prevents Lin41 autoubiquitination, stabilizing it to direct endodermal differentiation of mouse ESCs.

    Evidence In vitro kinase assay, Co-IP, Lin41 ubiquitination assay, ESC lineage marker analysis

    PMID:36660859

    Open questions at the time
    • Consensus motif or structural basis for PFKP substrate recognition as a kinase not defined
    • Whether PFKP kinase activity is relevant in adult tissues beyond ESCs not tested
  13. 2023 Medium

    Identification of lactylation at K688 as an inhibitory modification on PFKP enzymatic activity suggested a product-feedback mechanism where glycolysis-derived lactate attenuates PFKP.

    Evidence Proteome-wide lactylation profiling by MS, site-specific identification, in vitro enzyme activity assay

    PMID:38155775

    Open questions at the time
    • Lactyltransferase and delactylase for K688 not identified
    • In vivo relevance of K688 lactylation not tested in genetic models
    • Single study without independent replication
  14. 2024 Medium

    Multiple E3 ligases (RNF123, TRIM21 counteracted by PKP1) and the deubiquitinase USP5 were added to the PFKP ubiquitin regulatory network, reinforcing that PFKP protein turnover is a major control point for glycolysis across cancer types.

    Evidence Co-IP, ubiquitination assays, KD/OE with stability and glycolysis readouts for RNF123 (PMID:39725718), USP5 (PMID:38217030), and PKP1-TRIM21 (PMID:40890861)

    PMID:38217030 PMID:39725718 PMID:40890861

    Open questions at the time
    • Relative contributions of each E3/DUB pair in a single cell type not compared
    • Lysine specificity for most E3 ligase–PFKP pairs not mapped
  15. 2024 Medium

    PFKP was shown to participate in non-metabolic signaling by binding AXL to promote its Y779 phosphorylation and downstream MET activation, and by interacting with AMOTL1 to suppress Hippo pathway activity via YAP nuclear translocation.

    Evidence Co-IP and phosphorylation assays for PFKP-AXL (PMID:39664584); Co-IP, ubiquitination, YAP localization for PFKP-AMOTL1 (PMID:41727965)

    PMID:39664584 PMID:41727965

    Open questions at the time
    • Whether PFKP's kinase activity mediates AXL phosphorylation or acts via scaffolding not distinguished
    • PFKP-AMOTL1 interaction domain not mapped
    • Both findings from single labs
  16. 2024 Medium

    A PFKP–c-Myc positive feedback loop was defined in which c-Myc transcriptionally activates PFKP, while PFKP stabilizes c-Myc protein via ERK signaling; USP14-mediated deubiquitination feeds into this circuit.

    Evidence KD/OE, ERK assays, luciferase reporter in HNSCC (PMID:38982480); K48-deubiquitination assays, c-Myc ChIP for USP14, PDOs in pancreatic cancer (PMID:41812332)

    PMID:38982480 PMID:41812332

    Open questions at the time
    • How PFKP activates ERK (direct or indirect) is mechanistically undefined
    • Whether USP14 and USP5 are redundant for PFKP stabilization not tested
  17. 2025 Medium

    HIF-1α and Stat1 were confirmed as direct transcriptional activators of PFKP in macrophages, establishing PFKP as a convergence point for hypoxia and inflammatory signaling that drives M1 polarization and phagocytic glycolysis.

    Evidence ChIP-qPCR for HIF-1α binding to PFKP locus, MitoQ rescue (PMID:40356076); ChIP-qPCR + luciferase for Stat1 (PMID:41079919)

    PMID:40356076 PMID:41079919

    Open questions at the time
    • Whether HIF-1α and Stat1 act combinatorially or independently at the PFKP promoter not resolved
    • Contribution of PFKP versus other glycolytic enzymes to macrophage polarization not dissected
  18. 2026 High

    ATM-dependent phosphorylation at T278 was shown to convert PFKP tetramers to dimers that translocate to the nucleus and recruit CK2 to phosphorylate RAD51 at T13, directly linking PFKP to homologous recombination DNA repair.

    Evidence In vitro kinase assay (ATM→PFKP T278), native gel oligomeric shift, Co-IP of PFKP-CK2 and RAD51-BRCA2, HR repair assay

    PMID:42011782

    Open questions at the time
    • Whether nuclear dimeric PFKP retains glycolytic or kinase activity not tested
    • Structural basis of tetramer-to-dimer switch upon T278 phosphorylation not resolved
  19. 2026 High

    The opposing functional effects of lactylation at different sites were clarified: K688 lactylation activates PFKP enzymatic activity and confers cardioprotection under ischemia, contrasting with earlier evidence of K688 lactylation as inhibitory.

    Evidence Lactylome MS, K688E mutagenesis, enzyme activity assay, Seahorse metabolic profiling, LAD ischemia mouse model

    PMID:41919225

    Open questions at the time
    • Discrepancy between K688 lactylation being activating (PMID:41919225) versus inhibiting (PMID:38155775) needs resolution across cell types
    • Enzymes catalyzing K688 lactylation not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis for PFKP's non-canonical protein kinase activity — including the catalytic site, substrate recognition motif, and how it coexists with PFK-1 enzymatic function — remains undefined.
  • No crystal or cryo-EM structure of PFKP in its dimeric nuclear form
  • Full catalog of PFKP kinase substrates unknown
  • Whether PFKP's glycolytic, kinase, and scaffolding activities are simultaneously active or mutually exclusive not determined
  • Integrated quantitative model of PFKP post-translational regulation (ubiquitination, acetylation, lactylation, phosphorylation, O-GlcNAcylation) lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 4 GO:0098772 molecular function regulator activity 4 GO:0140096 catalytic activity, acting on a protein 4
Localization
GO:0005829 cytosol 3 GO:0005634 nucleus 2 GO:0005739 mitochondrion 2
Pathway
R-HSA-1430728 Metabolism 8 R-HSA-74160 Gene expression (Transcription) 8 R-HSA-162582 Signal Transduction 4 R-HSA-1640170 Cell Cycle 2 R-HSA-9612973 Autophagy 2 R-HSA-73894 DNA Repair 1
Partners
AMPKATG4BCCND3CDK6CK2TRIM25USP5VDAC2

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1983 The human PFKP gene was mapped to the short arm of chromosome 10 (10p) using somatic cell hybrid analysis with anti-human P subunit-specific antiserum and immunoprecipitation; a gene dosage effect was demonstrated in fibroblasts with duplication of 10p, confirming PFKP encodes the platelet/fibroblast isoform of phosphofructokinase. Somatic cell hybrid panel analysis, active-enzyme-immunoprecipitation, gene dosage experiment Human genetics High 6222962
2011 KLF4 directly binds the PFKP promoter and transcriptionally activates PFKP expression in breast cancer cells, increasing glycolytic activity (glucose uptake and lactate production); knockdown of KLF4 decreased glycolysis whereas overexpression increased it, without affecting other PFK isoforms. ChIP (KLF4 binding to PFKP promoter), luciferase reporter assay, KLF4 KD/OE with glycolysis measurements The Journal of biological chemistry High 21586797
2017 Snail (SNAI1) directly represses PFKP transcription during EMT, diverting glucose flux from glycolysis to the pentose phosphate pathway (PPP), increasing NADPH; PFKP knockdown rescues the metabolic reprogramming and cell death induced by Snail loss, placing PFKP downstream of Snail in the glycolysis-PPP switch. Snail KD/OE with PFKP expression and metabolic flux measurements, PFKP rescue experiments, in vivo metastasis assay Nature communications High 28176759
2018 VDAC2 (a mitochondrial outer membrane protein) physically couples with PFKP on the mitochondrion to inhibit PFKP-mediated glycolysis; disruption of VDAC2 de-represses PFKP activity and glycolysis, driving dedifferentiation of non-stem tumor cells to glioma stem cells, while PFK inhibitor clotrimazole blocks this phenotypic transition. Co-immunoprecipitation (VDAC2-PFKP), VDAC2 KD/OE with glycolysis and stem-cell marker assays, clotrimazole rescue Cell death & disease Medium 30250190
2019 Under hypoxia, oxidized ATM regulates PFKP at the translational level (via HIF1A) to promote intracellular citrate accumulation in triple-negative breast cancer; suppression of oxidized ATM reduces PFKP and citrate levels, while citrate accumulation activates AKT/ERK/MMP2/9 signaling to enhance invasion and metastasis. ATM inhibition/oxidation assays, PFKP protein-level measurements, metabolite (citrate) quantification, in vitro invasion and xenograft assays Cell death & disease Medium 30850587
2021 R-2-hydroxyglutarate inhibits FTO demethylase activity, leading to increased m6A methylation on PFKP mRNA; this prevents YTHDF2-mediated protection of PFKP mRNA, reducing PFKP protein and suppressing aerobic glycolysis in leukemia cells. PFKP knockdown recapitulates R-2HG-induced glycolytic inhibition. m6A-seq, PFKP mRNA stability assays, FTO/YTHDF2 KD, metabolic assays, in vivo leukemogenesis model Molecular cell High 33434505
2021 HRD1 (an E3 ubiquitin ligase) interacts with and co-localizes with PFKP in the cytoplasm, ubiquitinates PFKP and targets it for proteasomal degradation, thereby reducing PFKP expression and glycolytic activity in breast cancer cells. Mass spectrometry interactome, co-immunoprecipitation, immunofluorescence co-localization, ubiquitylation assay, HRD1 OE/KD with glycolysis and tumor growth readouts Cell communication and signaling : CCS High 33588886
2021 PFKP is a nucleocytoplasmic shuttling protein with functional nuclear export and nuclear localization sequences (NLS). Cyclin D3/CDK6 dimerizes with PFKP and exposes its NLS, facilitating interaction with importin 9 and nuclear translocation. Nuclear PFKP stimulates CXCR4 expression in a c-Myc-dependent manner to promote T-ALL invasion and leukemia homing/infiltration. NLS/NES mutagenesis, Co-IP (Cyclin D3/CDK6-PFKP, PFKP-importin 9), subcellular fractionation, CXCR4 reporter assays, in vivo leukemia infiltration model with CXCR4 antagonist rescue, IHC of patient samples The Journal of clinical investigation High 34255748
2021 YY1 transcription factor directly binds the PFKP gene regulatory elements and activates PFKP transcription in cooperation with BRD2/4 co-factors; mutagenesis of YY1-bound cis-elements and gene loss-of-function/rescue studies establish a YY1:BRD2/4-PFKP axis driving the Warburg effect in castration-resistant prostate cancer. ChIP-seq (cistrome), YY1 KD with PFKP rescue, mutagenesis of YY1-binding cis-elements, in vitro and in vivo tumor growth assays Nucleic acids research High 33849067
2021 PFKP facilitates phosphorylation of autophagy protein ATG4B at serine 34, functioning as a protein kinase; amino acid deprivation strengthens the PFKP-ATG4B interaction, PFKP phosphorylates ATG4B at S34 in vitro, enhancing ATG4B activity and autophagic flux (LC3-II turnover, p62 degradation). PFKP S386 phosphorylation is required for its kinase activity toward ATG4B. Tandem affinity purification + mass spectrometry, Co-IP (ATG4B-PFKP interaction), CRISPR/Cas9 PFKP KO, in vitro kinase assay, phospho-site mutagenesis Cellular signalling High 33607258
2021 TGF-β1 recruits the SMAD3-SP1 complex to the PFKP promoter to transcriptionally activate PFKP expression in renal proximal tubular epithelial cells, driving glycolysis and kidney interstitial fibrosis; AAV-mediated PFKP overexpression worsens fibrosis while PFKP knockdown is protective. ChIP-qPCR (SMAD3-SP1 binding to PFKP promoter), AAV-mediated PFKP KD/OE in mice (unilateral ureteral occlusion model), glycolysis and fibrosis quantification Cell death & disease High 38086793
2022 PFKP physically interacts with AMPK; upon glucose starvation, this interaction is enhanced and promotes mitochondrial recruitment of AMPK, which then phosphorylates acetyl-CoA carboxylase 2 (ACC2) to enhance long-chain fatty acid oxidation, supporting energy and redox homeostasis in NSCLC cells. Proteomics screen of AMPK-interacting proteins, Co-IP (PFKP-AMPK), mitochondrial fractionation, ACC2 phosphorylation assay, PFKP KD with FAO measurements Cell discovery High 35641476
2022 Fbxo7 promotes Cdk6-dependent phosphorylation of PFKP and Cdk6-independent ubiquitination of PFKP; Fbxo7-deficient T cells show reduced Cdk6 activity and increased glycolytic flux, demonstrating that the Fbxo7-Cdk6 axis suppresses PFKP activity and glycolysis. Substrate screen for Fbxo7, Fbxo7 KO in CD4+ T cells, Cdk6 activity assays, ubiquitination assay, metabolomics of activated T cells The Journal of cell biology High 35670764
2022 PFKP activation in podocytes maintains fructose-1,6-bisphosphate (FBP) levels; PFKP knockdown or inhibition reduces FBP, activates the RhoA/ROCK1 pathway, and causes cytoskeletal remodeling (foot process fusion), while PFKP overexpression rescues these defects in diabetic kidney disease. siRNA/plasmid-mediated PFKP KD/OE, targeted metabolomics (FBP measurement), RhoA/ROCK1 pathway analysis, PFKP inhibitor (clotrimazole) in diabetic mice, exogenous FBP rescue Frontiers in endocrinology Medium 35095764
2023 SIRT2 deacetylates PFKP at lysine 394 (mouse)/lysine 395 (human), reducing PFKP enzymatic activity; acetylation at this site is required for PFKP's glycolytic function and its role in phosphorylating ATG4B to activate LC3-associated phagocytosis (LAP) in macrophages. Ethanol exposure enhances SIRT2-PFKP interaction and suppresses phagocytosis. SIRT2 KD/pharmacological inhibition, acetylation site mutagenesis (K394), PFKP activity assays, Atg4B phosphorylation assay, LC3 activation assay, phagocytosis/LAP assays in macrophages, in vivo sepsis survival Frontiers in immunology High 36865524
2023 CMBL enhances TRIM25 binding to PFKP, leading to K48-linked ubiquitination and proteasomal degradation of PFKP; p53 transcriptionally activates CMBL in response to genotoxic stress, thereby suppressing glycolysis through PFKP degradation in colorectal cancer. Co-IP (CMBL-TRIM25-PFKP ternary complex), ubiquitination assay, CMBL OE/KD with PFKP stability and glycolysis measurements, p53 activation experiments Cell reports High 37967006
2023 PFKP lactylation at lysine 688 directly attenuates its enzymatic activity, forming a potential negative feedback loop in glycolysis where lactate production inhibits PFKP through lactylation. Mass spectrometry-based proteome-wide lactylation profiling, site-specific lactylation identification at K688, in vitro PFKP enzyme activity assay after lactylation iScience Medium 38155775
2023 Glycolytic enzyme Pfkp acts as a protein kinase that phosphorylates the developmental regulator Lin41 at serine residues; this phosphorylation stabilizes Lin41 by preventing its autoubiquitination and proteasomal degradation, permitting Lin41-mediated RNA destabilization of ectodermal markers to favor endodermal specification during murine ESC differentiation. In vitro kinase assay (Pfkp phosphorylating Lin41), Co-IP, Lin41 ubiquitination assay, ESC differentiation lineage marker analysis, Pfkp KD/OE EMBO reports High 36660859
2023 HIF-1α transcriptionally regulates PFKP as a target gene; HBO therapy suppresses hypoxia-induced HIF-1α expression and downstream PFKP transactivation in NSCLC cells, and in vivo HBO therapy inhibited tumor growth in a Pfkp-dependent manner. HIF-1α KD, luciferase reporter (PFKP transactivation), glycolytic flux modeling, in vivo LLC tumor model with Pfkp-dependence rescue Frontiers in oncology Medium 34367973
2024 USP5 deubiquitinase directly interacts with PFKP and mediates its deubiquitination and stabilization, preventing proteasomal degradation; USP5-mediated PFKP stabilization is essential for cancer cell aerobic glycolysis and TNBC progression. Co-IP, MS-based protein identification, in vitro binding assay, ubiquitination assay, USP5 KD/OE with PFKP stability and glycolysis measurements, tumor xenograft Breast cancer research : BCR High 38217030
2024 PFKP increases ERK-mediated stability of c-Myc protein, while c-Myc transcriptionally activates PFKP expression, forming a positive feedback loop driving HNSCC progression; co-targeting both synergistically inhibits tumor growth. PFKP/c-Myc KD/OE, ERK phosphorylation assays, c-Myc stability measurements, luciferase reporter (PFKP promoter), PDO and xenograft models Molecular cancer Medium 38982480
2024 RNF123 (E3 ubiquitin ligase) directly interacts with PFKP and induces its ubiquitination, promoting PFKP degradation and thereby suppressing glycolysis, cell viability, cell cycle progression, and colony formation in breast cancer cells. Co-IP, ubiquitination analysis, RNF123 OE/KD with PFKP protein levels and glycolysis assays, IHC, in vivo xenograft Naunyn-Schmiedeberg's archives of pharmacology Medium 39725718
2024 PFKP promotes OC progression through lactylation at lysine 392; K392 mutation diminishes PFKP lactylation, and PFKP depletion upregulates PTEN expression in hypoxic ovarian cancer cells, suggesting PFKP lactylation suppresses PTEN to drive glycolysis. Immunoprecipitation + Western blot for PFKP lactylation, K392 site-directed mutagenesis, PFKP KD with PTEN/glycolysis measurement, OC xenograft model Biochemical genetics Medium 39638933
2024 PKP1 (Plakophilin-1) stabilizes PFKP by binding TRIM21 and preventing TRIM21-mediated ubiquitination and degradation of PFKP; PKP1 depletion selectively reduces PFKP protein levels by enhancing its ubiquitination, and PFKP mediates the proliferative and metabolic role of PKP1 in lung squamous cell carcinoma. CRISPR KO screen, metabolic assays (OCR/ECAR), ubiquitination assay, Co-IP (PKP1-TRIM21-PFKP), PFKP functional rescue experiments Biomarker research Medium 40890861
2024 PFKP interacts with AMOTL1 in HNSCC cells, inhibiting AMOTL1's ubiquitin-mediated degradation; PFKP-driven glycolysis and EMT are AMOTL1-dependent, and PFKP promotes YAP nuclear translocation via AMOTL1, suppressing Hippo pathway activity to amplify glycolytic flux. Co-IP (PFKP-AMOTL1), ubiquitination analysis, PFKP/AMOTL1 KD/OE, YAP nuclear localization assays, in vivo xenograft Journal of translational internal medicine Medium 41727965
2024 PFKP binds AXL and promotes its phosphorylation at Y779, activating AXL signaling and subsequently promoting MET phosphorylation in NSCLC cells, representing a non-metabolic, oncogenic signaling function of PFKP. Co-IP (PFKP-AXL), phosphorylation assays (AXL Y779, MET), PFKP KD with AXL/MET signaling readouts, nanoparticle-mediated in vivo PFKP silencing International journal of biological sciences Medium 39664584
2024 PFKP interacts with EIF2S2 (eukaryotic translation initiation factor 2 subunit beta); in cardiac hypertrophy models, PFKP overexpression increases protein synthesis through EIF2S2, and EIF2S2 knockdown after PFKP overexpression reduces new protein synthesis and alleviates hypertrophy. IP-MS/MS (PFKP interactome), PFKP KO/OE in mice (TAC model) and NRCMs, EIF2S2 KD rescue, protein synthesis assay Biochimica et biophysica acta. Molecular basis of disease Medium 39419453
2025 O-linked N-acetylglucosamine (O-GlcNAc) transferase interaction with PFKP is enhanced by TCEP exposure, decreasing PFKP enzymatic activity and impairing glycolysis and pentose phosphate pathway function in platelets, thereby suppressing platelet activation processes. Proteomic analysis of platelets, OGT-PFKP interaction assay, PFKP activity measurement, ex vivo platelet activation assays, in vivo TCEP exposure model Environmental pollution Medium 39828204
2025 Stat1 transcription factor directly binds the Pfkp promoter (demonstrated by ChIP-qPCR) and transcriptionally activates Pfkp expression in macrophages downstream of dsHMGB1/Jak2/Stat1 signaling, promoting glycolysis and M1 macrophage polarization. ChIP-qPCR (Stat1 binding to Pfkp promoter), dual-luciferase assay, Stat1 inhibitor (fludarabine) rescue, macrophage polarization assays International journal of biological sciences Medium 41079919
2025 HIF-1α transcriptionally controls PFKP mRNA in macrophages; in ethanol-exposed macrophages, oxidative stress (ROS) impairs HIF-1α function, reducing PFKP transcription and dampening glycolysis and phagocytosis. MitoQ restores HIF-1α function, PFKP expression, glycolysis, and phagocytosis, validated by ChIP-qPCR. ChIP-qPCR (HIF-1α binding to PFKP locus), PFKP mRNA/protein measurements, MitoQ treatment, phagocytosis and glycolysis assays, in vivo sepsis survival Journal of immunology Medium 40356076
2026 ATM kinase phosphorylates PFKP at threonine 278 (T278) in response to ionizing radiation or high glucose, promoting transition of PFKP from tetramers to dimers and nuclear translocation of the dimeric form. Nuclear dimeric PFKP recruits casein kinase 2 (CK2), which phosphorylates RAD51 at T13, enhancing RAD51-BRCA2 interaction and homologous recombination repair efficiency. In vitro phosphorylation assay (ATM→PFKP T278), site-directed mutagenesis, native gel electrophoresis (tetramer/dimer shift), Co-IP (PFKP-CK2, RAD51-BRCA2), CK2 substrate assay (RAD51 T13), nuclear fractionation, HR repair assay Nucleic acids research High 42011782
2026 PFKP-K688 lactylation (PFKP-K688la) is induced by hypoxia/ischemia; this modification increases PFKP enzymatic activity and glycolytic flux while suppressing mitochondrial respiration. A K688E mutation mimicking hyper-lactylation amplifies glycolysis, and this modification provides cardioprotection in ischemic cardiomyocytes. Lactylome proteomics, PFKP-K688E mutagenesis, PFKP enzyme activity assay, Seahorse (ECAR/OCR), hypoxic cardiomyocyte and LAD mouse models Frontiers in pharmacology High 41919225
2026 USP14 deubiquitinase stabilizes PFKP through K48-linked deubiquitination, and c-Myc transcriptionally upregulates USP14; PFKP in turn enhances ERK-dependent c-Myc protein stability, forming a c-Myc-USP14-PFKP feed-forward circuit that sustains chemoresistance in pancreatic ductal adenocarcinoma. Ubiquitination assays (K48-linked), USP14 KD/OE with PFKP stability, c-Myc ChIP/reporter for USP14, ERK phosphorylation assay, patient-derived organoids, syngeneic/xenograft models Drug resistance updates Medium 41812332

Source papers

Stage 0 corpus · 56 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2021 R-2-hydroxyglutarate attenuates aerobic glycolysis in leukemia by targeting the FTO/m6A/PFKP/LDHB axis. Molecular cell 253 33434505
2017 Snail reprograms glucose metabolism by repressing phosphofructokinase PFKP allowing cancer cell survival under metabolic stress. Nature communications 145 28176759
2011 Krüppel-like factor 4 (KLF4) activates the transcription of the gene for the platelet isoform of phosphofructokinase (PFKP) in breast cancer. The Journal of biological chemistry 95 21586797
2020 PFKP is highly expressed in lung cancer and regulates glucose metabolism. Cellular oncology (Dordrecht, Netherlands) 81 32219704
2019 Intracellular citrate accumulation by oxidized ATM-mediated metabolism reprogramming via PFKP and CS enhances hypoxic breast cancer cell invasion and metastasis. Cell death & disease 76 30850587
2022 PFKP alleviates glucose starvation-induced metabolic stress in lung cancer cells via AMPK-ACC2 dependent fatty acid oxidation. Cell discovery 70 35641476
2018 Silencing PFKP inhibits starvation-induced autophagy, glycolysis, and epithelial mesenchymal transition in oral squamous cell carcinoma. Experimental cell research 62 29894707
2018 VDAC2 interacts with PFKP to regulate glucose metabolism and phenotypic reprogramming of glioma stem cells. Cell death & disease 58 30250190
2019 PFKP Signaling at a Glance: An Emerging Mediator of Cancer Cell Metabolism. Advances in experimental medicine and biology 51 30919341
2021 Cistrome analysis of YY1 uncovers a regulatory axis of YY1:BRD2/4-PFKP during tumorigenesis of advanced prostate cancer. Nucleic acids research 44 33849067
2023 Proteomic analysis identifies PFKP lactylation in SW480 colon cancer cells. iScience 43 38155775
2020 HOTAIRM1 knockdown enhances cytarabine-induced cytotoxicity by suppression of glycolysis through the Wnt/β-catenin/PFKP pathway in acute myeloid leukemia cells. Archives of biochemistry and biophysics 43 31904363
1983 Regional assignment of the human gene for platelet-type phosphofructokinase (PFKP) to chromosome 10p: novel use of polyspecific rodent antisera to localize human enzyme genes. Human genetics 43 6222962
2023 Inhibition of PFKP in renal tubular epithelial cell restrains TGF-β induced glycolysis and renal fibrosis. Cell death & disease 42 38086793
2021 Nuclear PFKP promotes CXCR4-dependent infiltration by T cell acute lymphoblastic leukemia. The Journal of clinical investigation 40 34255748
2008 Non-replication of genome-wide based associations between common variants in INSIG2 and PFKP and obesity in studies of 18,014 Danes. PloS one 40 18682847
2021 Anti-Warburg effect by targeting HRD1-PFKP pathway may inhibit breast cancer progression. Cell communication and signaling : CCS 31 33588886
2021 Hyperbaric Oxygen Therapy Represses the Warburg Effect and Epithelial-Mesenchymal Transition in Hypoxic NSCLC Cells via the HIF-1α/PFKP Axis. Frontiers in oncology 29 34367973
2023 p53-responsive CMBL reprograms glucose metabolism and suppresses cancer development by destabilizing phosphofructokinase PFKP. Cell reports 25 37967006
2019 Mutant IDH1 confers resistance to energy stress in normal biliary cells through PFKP-induced aerobic glycolysis and AMPK activation. Scientific reports 25 31827136
2024 PFKP deubiquitination and stabilization by USP5 activate aerobic glycolysis to promote triple-negative breast cancer progression. Breast cancer research : BCR 24 38217030
2024 A positive feedback loop between PFKP and c-Myc drives head and neck squamous cell carcinoma progression. Molecular cancer 24 38982480
2021 Silencing PFKP restrains the stemness of hepatocellular carcinoma cells. Experimental cell research 21 34418458
2023 SIRT2-PFKP interaction dysregulates phagocytosis in macrophages with acute ethanol-exposure. Frontiers in immunology 19 36865524
2023 The mRNA and protein levels of the glycolytic enzymes lactate dehydrogenase A (LDHA) and phosphofructokinase platelet (PFKP) are good predictors of survival time, recurrence, and risk of death in cervical cancer patients. Cancer medicine 18 37326348
2022 PFKP Activation Ameliorates Foot Process Fusion in Podocytes in Diabetic Kidney Disease. Frontiers in endocrinology 15 35095764
2021 Triptolide impairs glycolysis by suppressing GATA4/Sp1/PFKP signaling axis in mouse Sertoli cells. Toxicology and applied pharmacology 14 34087332
2023 Glycolysis regulator PFKP induces human melanoma cell proliferation and tumor growth. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 13 36792847
2023 PFKP: More than phosphofructokinase. Advances in cancer research 13 37704285
2023 PFKP confers chemoresistance by upregulating ABCC2 transporter in non-small cell lung cancer. Translational lung cancer research 12 38090515
2022 Fbxo7 promotes Cdk6 activity to inhibit PFKP and glycolysis in T cells. The Journal of cell biology 11 35670764
2024 Effect of lncRNA XIST on acute myeloid leukemia cells via miR-142-5p-PFKP axis. Hematology (Amsterdam, Netherlands) 10 38305210
2024 PFKP Lactylation Promotes the Ovarian Cancer Progression Through Targeting PTEN. Biochemical genetics 9 39638933
2021 PFKP facilitates ATG4B phosphorylation during amino acid deprivation-induced autophagy. Cellular signalling 9 33607258
2023 Glycolytic Pfkp acts as a Lin41 protein kinase to promote endodermal differentiation of embryonic stem cells. EMBO reports 7 36660859
2024 PFKP inhibition protects against pathological cardiac hypertrophy by regulating protein synthesis. Biochimica et biophysica acta. Molecular basis of disease 4 39419453
2024 PFKP silencing suppresses tumor growth via the AXL-MET axis. International journal of biological sciences 4 39664584
2024 RNF123 inhibits cell viability, cell cycle and colony formation of breast cancer by inhibiting glycolysis via ubiquitination of PFKP. Naunyn-Schmiedeberg's archives of pharmacology 4 39725718
2023 PFKP is upregulated in 5-fluorouracil-resistant patients and suppresses the antitumor activity of 5-fluorouracil in colorectal cancer in vitro and in vivo. Journal of chemotherapy (Florence, Italy) 4 38044588
2025 PKP1 promotes lung cancer by modulating energy metabolism through stabilization of PFKP. Biomarker research 3 40890861
2022 PFKP and GPC6 Variants Were Correlated with Alcohol-Induced Femoral Head Necrosis Risk in the Chinese Han Population. Pharmacogenomics and personalized medicine 3 36110408
2025 Inhibition of platelet activation process upon tris (2-chloroethyl) phosphate exposure: Role of PFKP-mediated glycolysis and the pentose phosphate pathway. Environmental pollution (Barking, Essex : 1987) 2 39828204
2025 Mitoquinol improves phagocytosis and glycolysis in ethanol-exposed macrophages via HIF-1α-PFKP axis. Journal of immunology (Baltimore, Md. : 1950) 2 40356076
2024 Silencing circLDLRAD3 Inhibits Lung Cancer Progression by Regulating the miR-497-5p/PFKP Axis. Molecular biotechnology 2 38427179
2025 Gen-miR-5 derived from Gentianella acuta inhibits PFKP to prevent fibroblast activation and alleviate myocardial fibrosis. Frontiers in pharmacology 1 40385478
2025 dsHMGB1, released from IL-17A-induced pyroptotic prostate epithelial cells, drives M1 polarization by promoting Pfkp-mediated glycolysis via Jak2/Stat1 transcription in experimental autoimmune prostatitis. International journal of biological sciences 1 41079919
2026 PFKP binding AMOTL1 promotes tumor aerobic glycolysis and epithelial-mesenchymal transition by modulating Hippo pathway in head and neck cancer. Journal of translational internal medicine 0 41727965
2026 The c-Myc-USP14-PFKP axis sustains chemoresistance in pancreatic ductal adenocarcinoma. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy 0 41812332
2026 Lactylation of PFKP-K688 enhances glycolytic flux and confers cardioprotection in myocardial ischemia. Frontiers in pharmacology 0 41919225
2026 ATM promotes PFKP nuclear translocation to balance glycolysis and homologous recombination repair. Nucleic acids research 0 42011782
2026 PFKP is required for chemoresistant phenotype of breast cancer through modulating the formation of CD133+ cancer stem like cells. Molecular biomedicine 0 42024199
2026 PFKP Drives Immune Checkpoint Co-Expression and Metabolic Pathway Activation in Liver Cancer: TCGA-Based and Experimental Validation. Clinical and translational gastroenterology 0 42044203
2025 TRIM25 potentiates innate immune response to Senecavirus A by enhancing K63-linked ubiquitination of RIG-I and K48-linked ubiquitin-facilitated degradation of PFKP. Veterinary microbiology 0 40651151
2025 P4HA2 promotes the progression of thyroid cancer by regulating PFKP-mediated glycolysis. Journal of physiology and biochemistry 0 40762768
2025 PFKP Mediates Breast Cancer Metastasis Through Altered Glycolysis. Cureus 0 40821334
2025 Integrative analysis of single-cell and bulk transcriptomes reveals metabolic heterogeneity and identifies PFKP as a therapeutic target in cervical cancer. Biochimica et biophysica acta. Molecular basis of disease 0 41448552