Affinage

PFKP

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

Length
784 aa
Mass
85.6 kDa
Annotated
2026-06-10
57 papers in source corpus 35 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PFKP (platelet-type phosphofructokinase) is a rate-limiting glycolytic enzyme whose expression, stability, and moonlighting activities place it at the convergence of metabolic flux control, autophagy, DNA repair, and oncogenic signaling (PMID:28176759, PMID:33607258, PMID:42011782). Its glycolytic output is controlled at multiple levels: a broad transcriptional network activates PFKP — KLF4 (PMID:21586797), YY1 with BRD2/4 (PMID:33849067), HIF-1α (PMID:40356076), Stat1 (PMID:41079919), SMAD3–SP1 (PMID:38086793), GATA4/Sp1 (PMID:34087332), and a c-Myc positive-feedback loop (PMID:38982480) — while Snail represses it to divert glucose into the pentose phosphate pathway (PMID:28176759), and p53 represses it indirectly by inducing CMBL (PMID:37967006). PFKP protein stability is set by competing ubiquitin machineries, with the E3 ligases HRD1 (PMID:33588886), TRIM25 (bridged by CMBL) (PMID:37967006), RNF123 (PMID:39725718), and TRIM21 (PMID:40890861) driving proteasomal degradation, and the deubiquitinases USP5 (PMID:38217030) and USP14 (PMID:41812332) (the latter in a c-Myc–USP14–PFKP feed-forward circuit) stabilizing it. PFKP enzymatic activity is further tuned by post-translational modification, including SIRT2-mediated deacetylation at K394/K395 (PMID:36865524), lactylation at K688 and K392 (PMID:38155775, PMID:39638933, PMID:41919225), and O-GlcNAcylation (PMID:39828204). Beyond catalysis, PFKP acts as a non-canonical protein kinase, phosphorylating ATG4B-S34 to promote autophagic flux (PMID:33607258) and Lin41 to stabilize it and direct endodermal differentiation in stem cells (PMID:36660859). PFKP shuttles between cytoplasm and nucleus via mapped NLS/NES sequences, with Cyclin D3/CDK6 and importin 9 driving nuclear entry to transcriptionally activate CXCR4 through c-Myc (PMID:34255748); upon ATM-mediated T278 phosphorylation it shifts from tetramer to dimer and recruits CK2 to phosphorylate RAD51-T13, supporting homologous recombination repair (PMID:42011782). It also exerts protein-binding functions independent of catalysis, recruiting AMPK to mitochondria to drive fatty acid oxidation (PMID:35641476), activating AXL receptor signaling (PMID:39664584), and stabilizing AMOTL1 to promote YAP nuclear translocation (PMID:41727965).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1983 High

    Establishing the chromosomal location of the platelet PFK subunit gene was the first step in defining PFKP as a distinct, dosage-sensitive genetic locus.

    Evidence Somatic cell hybrid panel with active-enzyme immunoprecipitation and gene-dosage analysis in fibroblasts

    PMID:6222962

    Open questions at the time
    • Did not address tissue-specific regulation or non-glycolytic functions
    • No protein-level mechanism beyond enzyme dosage
  2. 2011 Medium

    Identifying KLF4 as a direct PFKP promoter activator showed PFKP transcription is selectively wired into oncogenic glycolytic programs distinct from other PFK isoforms.

    Evidence Promoter binding (ChIP/reporter), KLF4 knockdown/overexpression and glucose/lactate assays in breast cancer cells

    PMID:21586797

    Open questions at the time
    • Single lab
    • Did not connect KLF4 to upstream signals controlling PFKP
  3. 2017 High

    Demonstrating Snail-mediated PFKP repression established PFKP as a metabolic switch directing glucose between glycolysis and the pentose phosphate pathway during EMT.

    Evidence Snail and PFKP knockdown/rescue with metabolic flux assays and in vivo metastasis models

    PMID:28176759

    Open questions at the time
    • Mechanism of Snail recruitment to PFKP locus not detailed
    • PPP rerouting quantified but enzymatic regulation downstream of repression not addressed
  4. 2018 Medium

    Linking PFKP to VDAC2 at mitochondria revealed that spatial restriction of PFKP activity controls glioma stemness.

    Evidence Co-localization, VDAC2 manipulation, PFK inhibitor rescue and stem/tumorigenicity assays

    PMID:30250190

    Open questions at the time
    • Interaction inferred from co-localization and inhibitor rescue rather than direct binding
    • Single lab
  5. 2019 Medium

    Defining an ATM→HIF1A→PFKP translational axis under hypoxia connected PFKP-derived citrate accumulation to invasive signaling.

    Evidence ATM inhibition/knockdown, HIF1A studies, citrate measurement and invasion/xenograft assays in breast cancer

    PMID:30850587

    Open questions at the time
    • Translational regulation mechanism not molecularly resolved
    • Single lab
  6. 2019 Medium

    Mutant IDH1 was shown to upregulate PFKP via altered histone modification, tying oncometabolite-driven epigenetics to glycolytic gene expression.

    Evidence Expression analysis, ChIP for histone marks, organoid PFKP knockdown and patient IHC

    PMID:31827136

    Open questions at the time
    • Specific histone mark and reader at PFKP locus not defined
    • Single lab
  7. 2021 High

    Multiple 2021 studies revealed PFKP is controlled post-transcriptionally (FTO/m6A/YTHDF2), by ubiquitin-mediated degradation (HRD1), and by direct transcriptional activation (YY1:BRD2/4), broadening the regulatory network governing PFKP abundance.

    Evidence m6A-seq with genetic rescue in leukemia; MS, reciprocal Co-IP and ubiquitination assays for HRD1; cistrome mapping and cis-element mutagenesis for YY1

    PMID:33434505 PMID:33588886 PMID:33849067

    Open questions at the time
    • How these layers integrate to set net PFKP levels in a given cell not addressed
    • Each established in distinct cancer contexts
  8. 2021 High

    Discovery that PFKP phosphorylates ATG4B-S34 redefined PFKP as a non-canonical protein kinase coupling metabolic state to autophagy.

    Evidence TAP-MS, in vitro kinase assay, phosphosite MS and CRISPR knockout autophagic flux assays under amino acid deprivation

    PMID:33607258

    Open questions at the time
    • Structural basis of PFKP kinase activity unresolved
    • Whether kinase and glycolytic activities are mutually exclusive not addressed
  9. 2021 High

    Mapping functional NLS/NES sequences and Cyclin D3/CDK6–importin 9-driven nuclear import established PFKP as a shuttling protein with a nuclear transcriptional function (CXCR4 via c-Myc).

    Evidence NLS/NES mapping, importin 9 Co-IP, nuclear fractionation, CXCR4 assays and in vivo homing/antagonist rescue in T-ALL

    PMID:34255748

    Open questions at the time
    • Whether nuclear PFKP retains catalytic activity not resolved
    • Direct DNA contact vs c-Myc cofactor role not distinguished
  10. 2022 High

    Identifying PFKP–AMPK and CDK6–Fbxo7 axes showed PFKP both directs mitochondrial AMPK signaling under starvation and serves as an essential CDK6 substrate in T cells.

    Evidence Proteomics and Co-IP with ACC2 phosphorylation/FAO assays (AMPK); Fbxo7 substrate screen with metabolomics and ubiquitination/phosphorylation assays in CD4+ T cells (CDK6/Fbxo7)

    PMID:35641476 PMID:35670764

    Open questions at the time
    • Functional residue(s) of CDK6 phosphorylation on PFKP not mapped
    • Crosstalk between PFKP scaffolding and catalysis not resolved
  11. 2022 Medium

    Demonstrating that PFKP product FBP inhibits RhoA/ROCK1 in podocytes linked PFKP catalytic output to cytoskeletal protection in a non-cancer setting.

    Evidence AAV PFKP manipulation in mouse kidney, targeted metabolomics, exogenous FBP addition and RhoA/ROCK1 readouts

    PMID:35095764

    Open questions at the time
    • Direct FBP–RhoA/ROCK1 mechanism not biochemically defined
    • Single lab
  12. 2023 High

    A series of 2023 studies established the PTM and degradation logic of PFKP: lactylation (K688), deacetylation (K394/K395 by SIRT2), and CMBL-bridged TRIM25 ubiquitination under p53 control, each tuning enzymatic activity or stability.

    Evidence MS lactylation profiling with activity assays; SIRT2 KO/inhibition with ATG4B/LAP readouts; reciprocal Co-IP of CMBL–TRIM25–PFKP with ubiquitination and p53 epistasis

    PMID:36865524 PMID:37967006 PMID:38155775

    Open questions at the time
    • Interplay among competing PTMs on the same protein not integrated
    • Stoichiometry and dynamics of modifications in vivo unclear
  13. 2023 High

    Identifying PFKP as a kinase for Lin41 extended its non-canonical kinase role to stem cell lineage control, stabilizing Lin41 to favor endodermal differentiation.

    Evidence Pfkp manipulation, in vitro/in vivo Lin41 kinase and ubiquitination assays, mESC lineage marker assays

    PMID:36660859

    Open questions at the time
    • Lin41 target serine residues not fully enumerated
    • Relationship to ATG4B kinase activity not addressed
  14. 2023 Medium

    Adding SMAD3-SP1 (TGF-β1), GATA4/Sp1, and NF-κB–ABCC2 links expanded PFKP's roles to kidney fibrosis, Sertoli cell glycolysis, and NSCLC drug resistance.

    Evidence ChIP-qPCR with AAV in vivo fibrosis models; GATA4/Sp1 knockdown with glycolysis assays; PFKP–NF-κB–ABCC2 luciferase and cisplatin sensitivity assays

    PMID:34087332 PMID:38086793 PMID:38090515

    Open questions at the time
    • Each axis from a single lab
    • Whether glycolytic vs moonlighting activity drives these phenotypes not always distinguished
  15. 2024 Medium

    2024 work deepened the PFKP stability and signaling map, adding USP5 and RNF123 to the ubiquitin axis, a c-Myc/ERK feedback loop, and lactylation at K392 regulating PTEN.

    Evidence Co-IP, in vitro binding and ubiquitination assays (USP5, RNF123); ERK/c-Myc stability and ChIP (HNSCC); K392 mutagenesis with PTEN/glycolysis readouts (ovarian cancer)

    PMID:38217030 PMID:38982480 PMID:39638933 PMID:39725718

    Open questions at the time
    • Competing E3/DUB activities not reconciled into a unified stability model
    • Most findings single-lab and context-specific
  16. 2024 Medium

    Identifying PFKP binding partners AXL, EIF2S2, and AMOTL1 expanded its catalysis-independent scaffolding functions into receptor signaling, protein synthesis, and cardiac hypertrophy.

    Evidence Co-IP/MS with AXL Y779 and MET phosphorylation assays; LC-MS/MS with EIF2S2 rescue in TAC model; AMOTL1 binding/ubiquitination and YAP/Hippo assays

    PMID:39419453 PMID:39664584 PMID:41727965

    Open questions at the time
    • Direct vs bridged interactions not always distinguished
    • Single-lab findings across distinct disease contexts
  17. 2025 Medium

    Showing HIF-1α, Stat1, and PKP1/TRIM21 each control PFKP refined macrophage and squamous-cancer regulation, including a PKP1-mediated block of TRIM21 ubiquitination.

    Evidence ChIP-qPCR and pharmacological rescue for HIF-1α and Stat1 in macrophages; CRISPR screening, TRIM21 binding and ubiquitination/rescue assays for PKP1 in LUSC

    PMID:40356076 PMID:40890861 PMID:41079919

    Open questions at the time
    • O-GlcNAc and other PTM cross-regulation in immune cells not integrated
    • Most studies single-lab
  18. 2025 Medium

    Demonstrating that O-GlcNAc transferase interaction lowers PFKP activity in platelets connected PFKP-controlled glycolysis to platelet aggregation and a toxicant exposure phenotype.

    Evidence Platelet proteomics, OGT–PFKP interaction and activity assays with ATP/aggregation readouts

    PMID:39828204

    Open questions at the time
    • O-GlcNAc site on PFKP not mapped
    • Single lab
  19. 2026 High

    Defining ATM–T278 phosphorylation that drives a tetramer-to-dimer transition and nuclear CK2 recruitment established PFKP as a direct participant in homologous recombination DNA repair.

    Evidence In vitro ATM kinase assay, T278 mutagenesis, oligomeric state analysis, CK2 Co-IP and RAD51-T13/HR repair assays under irradiation and high glucose

    PMID:42011782

    Open questions at the time
    • Structural basis of dimer-specific CK2 recruitment not resolved
    • Whether dimeric PFKP retains glycolytic catalysis unclear
  20. 2026 Medium

    Adding a c-Myc–USP14–PFKP feed-forward circuit and a context-dependent K688 lactylation that enhances activity in cardiomyocytes refined PFKP stability control and reconciled tissue-specific PTM effects.

    Evidence K48-linked ubiquitination, USP14 interaction and ERK–c-Myc circuit in PDAC models; cardiac lactylome proteomics with K688E mutagenesis and activity/survival assays

    PMID:41812332 PMID:41919225

    Open questions at the time
    • Opposite directionality of K688 lactylation effect between cancer and cardiomyocytes mechanistically unexplained
    • Single-lab findings

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PFKP's catalytic, kinase, scaffolding, and nuclear functions are coordinately switched within a single cell, and what structural features distinguish its glycolytic from non-canonical activities, remains unresolved.
  • No structural model reconciling tetramer/dimer states with kinase and scaffold activities
  • Integration of competing E3/DUB and PTM inputs into net activity unknown
  • Context-dependent lactylation effects unexplained at the mechanistic level

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 3 GO:0140096 catalytic activity, acting on a protein 2 GO:0140110 transcription regulator activity 1
Localization
GO:0005634 nucleus 2 GO:0005739 mitochondrion 2 GO:0005829 cytosol 1
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-1430728 Metabolism 3 R-HSA-168256 Immune System 3 R-HSA-162582 Signal Transduction 2 R-HSA-9612973 Autophagy 2 R-HSA-73894 DNA Repair 1 R-HSA-74160 Gene expression (Transcription) 1
Partners
AMOTL1AMPKATG4BAXLEIF2S2TRIM25USP5VDAC2
Complex memberships
CMBL–TRIM25–PFKP ubiquitination complex

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1983 The PFKP locus was mapped to the short arm of human chromosome 10 (10p) using human X rodent somatic cell hybrids with active-enzyme immunoprecipitation; gene dosage effects were confirmed in fibroblasts with 10p duplication showing ~180% normal PFK activity. Somatic cell hybrid panel, active-enzyme immunoprecipitation with rodent anti-human P subunit-specific antiserum, gene dosage analysis Human genetics High 6222962
2011 KLF4 transcriptionally activates PFKP by directly binding the PFKP promoter in breast cancer cells, increasing glucose uptake and lactate production; knockdown of KLF4 reduced these glycolytic outputs specifically for the PFKP isoform without affecting other PFK isoforms. Promoter binding (ChIP/reporter assay), KLF4 knockdown and overexpression, glucose/lactate metabolic assays The Journal of biological chemistry Medium 21586797
2017 Snail (SNAI1) transcriptionally represses PFKP in cancer cells undergoing EMT, diverting glucose flux from glycolysis toward the pentose phosphate pathway (PPP) and generating NADPH; knockdown of PFKP rescues the metabolic reprogramming and cell death induced by loss of Snail. Snail knockdown/overexpression, PFKP knockdown/rescue, metabolic flux assays (NADPH, PPP metabolites), in vivo metastasis assays Nature communications High 28176759
2018 VDAC2 (a mitochondrial outer membrane protein) couples with PFKP on mitochondria to inhibit PFKP-mediated glycolysis; disruption of VDAC2 de-represses PFKP activity and drives non-stem glioma cells toward a stem cell phenotype, an effect blocked by PFK inhibitor clotrimazole. Co-expression analysis, VDAC2 overexpression/knockdown, PFK inhibitor (clotrimazole), stem cell marker assays, tumorigenicity assays Cell death & disease Medium 30250190
2019 Under hypoxia, oxidized ATM (DNA damage-independent activation) promotes upregulation of PFKP at the translational level via HIF1A, leading to intracellular citrate accumulation that enhances breast cancer cell migration and invasion through AKT/ERK/MMP2/9 signaling. ATM inhibition/knockdown, HIF1A regulation studies, PFKP protein/mRNA assays, citrate measurement, invasion/migration assays, xenograft experiments Cell death & disease Medium 30850587
2021 R-2-hydroxyglutarate (R-2HG) suppresses aerobic glycolysis in leukemia cells by inhibiting FTO-mediated m6A demethylation, which abrogates YTHDF2-dependent post-transcriptional upregulation of PFKP (and LDHB) mRNA; knockdown of FTO or PFKP phenocopies R-2HG-induced glycolytic inhibition, and PFKP overexpression reverses R-2HG effects. m6A sequencing, FTO/PFKP knockdown and overexpression, glycolysis assays, in vivo leukemogenesis models, primary AML cells Molecular cell High 33434505
2021 HRD1 (E3 ubiquitin ligase) interacts and co-localizes with PFKP in the cytoplasm, ubiquitinates PFKP targeting it for proteasomal degradation, and thereby reduces PFKP expression and enzymatic activity, suppressing aerobic glycolysis and breast cancer growth in a PFKP-dependent manner. Mass spectrometry, co-immunoprecipitation, immunofluorescence co-localization, ubiquitination assay, PFKP activity assay, in vivo xenograft Cell communication and signaling : CCS High 33588886
2021 YY1 transcription factor directly binds and transcriptionally activates the PFKP gene promoter in prostate cancer cells, forming an oncogenic YY1:BRD2/4-PFKP axis that sustains the Warburg effect; mutagenesis of YY1-bound cis-elements and gene loss-of-function/rescue studies confirmed the direct transcriptional regulation. Cistrome analysis (ChIP-seq), gene loss-of-function, YY1-bound cis-element mutagenesis, gene rescue studies, interactome profiling Nucleic acids research High 33849067
2021 PFKP is a nucleocytoplasmic shuttling protein containing functional nuclear export and nuclear localization sequences (NLS). Cyclin D3/CDK6 promotes PFKP nuclear translocation by dimerization and by exposing the NLS, enabling interaction with importin 9. In the nucleus, PFKP stimulates CXCR4 expression via c-Myc activity to promote T-ALL cell invasion. NLS/NES mapping, Cyclin D3/CDK6 overexpression, importin 9 co-immunoprecipitation, PFKP nuclear fractionation, CXCR4 expression assays, in vivo leukemia homing assays, CXCR4 antagonist rescue The Journal of clinical investigation High 34255748
2021 PFKP phosphorylates ATG4B at serine 34 (S34) in vitro, functioning as a protein kinase; amino acid deprivation strengthens the PFKP-ATG4B interaction, and this PFKP-mediated ATG4B phosphorylation enhances ATG4B activity and autophagic flux. PFKP S386 phosphorylation (under starvation) is required for ATG4B S34 phosphorylation. Tandem affinity purification-mass spectrometry, immunoprecipitation, in vitro kinase assay, CRISPR/Cas9 PFKP knockout, phosphosite mass spectrometry, autophagic flux assays Cellular signalling High 33607258
2021 Mutant IDH1 upregulates PFKP expression through alteration of histone modification (as revealed by ChIP), and PFKP knockdown alleviates the mutant IDH1-induced increase in intrahepatic biliary organoid formation; high PFKP expression is more frequent in IDH-mutant cholangiocarcinoma. Gene expression analysis, ChIP for histone modification, Pfkp knockdown in intrahepatic biliary organoids, patient tissue immunohistochemistry Scientific reports Medium 31827136
2022 PFKP interacts with AMPK; upon glucose starvation this interaction is greatly enhanced and promotes mitochondrial recruitment of AMPK, which then phosphorylates ACC2 to enhance long-chain fatty acid oxidation, maintaining energy/redox homeostasis and promoting cancer cell survival. Proteomics screening of AMPK-interacting proteins, co-immunoprecipitation, PFKP knockdown/overexpression, ACC2 phosphorylation assays, fatty acid oxidation assays, metabolic measurements Cell discovery High 35641476
2022 Fbxo7 promotes Cdk6-dependent phosphorylation of PFKP and Cdk6-independent ubiquitination of PFKP; loss of Fbxo7 reduces Cdk6 activity leading to increased glycolysis in CD4+ T cells, establishing PFKP as an essential Cdk6 substrate in T cells. Fbxo7 substrate screen, Fbxo7-deficient cells, metabolomics of activated CD4+ T cells, Cdk6 activity assays, ubiquitination assays, PFKP phosphorylation assays The Journal of cell biology High 35670764
2022 PFKP promotes accumulation of its product fructose-1,6-bisphosphate (FBP); FBP inhibits RhoA/ROCK1 pathway-mediated cytoskeletal remodeling in podocytes, and PFKP overexpression rescues podocytes from high-glucose-induced cytoskeletal remodeling via this FBP-dependent mechanism. AAV-mediated PFKP overexpression/knockdown in mouse kidneys, siRNA in PTECs, targeted metabolomics, FBP measurement, FBP exogenous addition, RhoA/ROCK1 pathway assays, aldolase B manipulation Frontiers in endocrinology Medium 35095764
2023 PFKP is lactylated at lysine 688 (K688), and this modification directly attenuates PFKP enzymatic activity, suggesting a negative feedback loop in glycolysis where lactate production leads to PFKP inhibition via lactylation. Mass spectrometry proteome-wide lactylation profiling, identification of PFKP K688 lactylation site, enzymatic activity assay of lactylated vs. non-lactylated PFKP iScience Medium 38155775
2023 CMBL (carboxymethylenebutenolidase-like) bridges TRIM25 E3 ubiquitin ligase to PFKP; ectopic CMBL enhances TRIM25 binding to PFKP, leading to PFKP ubiquitination and proteasomal degradation. p53 transcriptionally activates CMBL in response to genotoxic stress, repressing glycolysis via PFKP degradation. Co-immunoprecipitation (CMBL-TRIM25-PFKP ternary complex), ubiquitination assay, p53 transcriptional activation analysis, proteasome inhibition, CMBL/TRIM25 KO with PFKP rescue Cell reports High 37967006
2023 TGF-β1 recruits the SMAD3-SP1 transcriptional complex to the PFKP promoter (confirmed by ChIP-qPCR) to enhance PFKP expression, upregulating glycolysis in renal proximal tubular epithelial cells and promoting kidney fibrosis; PFKP knockdown or overexpression in AAV-transduced mice correspondingly reduced or promoted fibrosis. ChIP-qPCR, AAV-mediated PFKP overexpression/knockdown in mouse kidneys, TGF-β1 stimulation of PTECs, glycolysis assays, fibrosis histology Cell death & disease High 38086793
2023 SIRT2 deacetylates PFKP at mouse lysine 394 (human K395), impairing its glycolytic function and reducing ATG4B phosphorylation; reduced ATG4B activation leads to decreased LC3 activation, suppressed LC3-associated phagocytosis (LAP), and impaired pathogen clearance in ethanol-exposed macrophages. Bone marrow-derived macrophages from SIRT2-deficient mice, SIRT2 pharmacological inhibition, PFKP acetylation/deacetylation assays, ATG4B phosphorylation, LC3 activation assays, phagocytosis/LAP assays, bacterial clearance and sepsis survival Frontiers in immunology High 36865524
2023 Glycolytic enzyme PFKP acts as a protein kinase for Lin41 in mouse embryonic stem cells: Pfkp phosphorylates Lin41 at serine residues, stabilizing Lin41 by impeding its autoubiquitination and proteasomal degradation; this allows Lin41 to destabilize ectodermal specification mRNAs and favor endodermal differentiation. Pfkp genetic manipulation (Stat3 repression model), in vitro/in vivo kinase assay for Lin41 phosphorylation, Lin41 ubiquitination assays, mESC differentiation lineage marker assays EMBO reports High 36660859
2023 Triptolide (TP) inhibits PFKP expression in Sertoli cells through the GATA4/Sp1 transcriptional axis: GATA4 regulates Sp1, which drives PFKP expression; suppression of GATA4 or Sp1 reduces PFKP levels and impairs glycolysis. GATA4/Sp1 knockdown, Sp1 pharmacological inhibitor (plicamycin), PFKP mRNA/protein assays, glucose/lactate assays, in vivo mouse TP dosing Toxicology and applied pharmacology Medium 34087332
2023 PFKP confers cisplatin resistance in NSCLC by upregulating the drug efflux transporter ABCC2 through activation of the NF-κB pathway (increased phospho-IκBα and nuclear p65); PFKP knockdown reduces NF-κB activation and ABCC2 expression, sensitizing cells to cisplatin. PFKP overexpression/knockdown in NSCLC cell lines, luciferase assay for ABCC2 promoter, NF-κB signaling assays (p-IκBα, nuclear p65), cisplatin sensitivity (flow cytometry), in vivo xenograft Translational lung cancer research Medium 38090515
2024 USP5 deubiquitinase directly binds PFKP and removes ubiquitin chains, stabilizing PFKP protein; USP5-mediated PFKP deubiquitination is essential for aerobic glycolysis and TNBC progression, with strong positive correlation between USP5 and PFKP levels in patient tissue. Co-immunoprecipitation, mass spectrometry protein identification, in vitro binding assay, ubiquitin assay, glycolysis assays, xenograft experiments, CPTAC database and IHC Breast cancer research : BCR High 38217030
2024 PFKP increases ERK-mediated stabilization of c-Myc protein, and c-Myc transcriptionally activates PFKP, forming a positive feedback loop that drives HNSCC progression; genetic and pharmacological co-targeting of PFKP and c-Myc shows synergistic anti-tumor effects in patient-derived organoids and xenografts. PFKP and c-Myc overexpression/knockdown, ERK signaling assays, c-Myc protein stability assays, c-Myc ChIP/transcriptional activation at PFKP, PDO and CDX/PDX models Molecular cancer Medium 38982480
2024 RNF123 E3 ubiquitin ligase directly interacts with PFKP and induces its ubiquitination and degradation, thereby inhibiting glycolysis, cell cycle progression, and viability of breast cancer cells; overexpression of PFKP reverses the tumor-suppressive effects of RNF123. Co-immunoprecipitation, ubiquitination analysis, glycolysis assays, cell viability/cycle/colony formation assays, in vivo xenograft, lentiviral overexpression/silencing Naunyn-Schmiedeberg's archives of pharmacology Medium 39725718
2024 PFKP is lactylated at lysine 392 (K392); mutation of K392 diminishes PFKP lactylation and reduces glycolysis; PFKP K392 lactylation promotes glycolysis by regulating PTEN expression in hypoxia-treated ovarian cancer cells. Immunoprecipitation-western blot for PFKP lactylation, K392 site-directed mutagenesis, PFKP knockdown/overexpression, glycolysis assays, PTEN expression analysis, xenograft model Biochemical genetics Medium 39638933
2024 PFKP binds AXL receptor tyrosine kinase and promotes its phosphorylation at Y779, activating AXL signaling and downstream MET phosphorylation in NSCLC cells, representing a non-metabolic oncogenic function of PFKP. PFKP knockdown (nanoparticle-mediated), co-immunoprecipitation of PFKP-AXL, AXL Y779 phosphorylation assays, MET phosphorylation assays, in vivo tumor growth International journal of biological sciences Medium 39664584
2024 PFKP interacts with EIF2S2 (eukaryotic translation initiation factor 2 subunit beta); PFKP overexpression promotes new protein synthesis via EIF2S2, contributing to pathological cardiac hypertrophy; knockdown of EIF2S2 after PFKP overexpression reduces new protein synthesis and alleviates hypertrophy. Immunoprecipitation combined with LC-MS/MS to identify PFKP interactors, EIF2S2 knockdown rescue in NRCM and TAC mouse model, protein synthesis assays, cardiac phenotype characterization Biochimica et biophysica acta. Molecular basis of disease Medium 39419453
2025 PKP1 (Plakophilin-1) stabilizes PFKP by binding TRIM21 and preventing TRIM21-mediated ubiquitination and proteasomal degradation of PFKP; PKP1 depletion selectively reduces PFKP levels, and functional rescue with PFKP restores the proliferative phenotype driven by PKP1. CRISPR knockout screening, PKP1 depletion, PFKP ubiquitination assays, TRIM21 binding assay, PFKP rescue experiments, metabolic assays (OCR/ECAR), multiple LUSC cell lines Biomarker research Medium 40890861
2025 HIF-1α transcriptionally controls PFKP mRNA in macrophages, as demonstrated by chromatin immunoprecipitation-qPCR (ChIP-qPCR); ethanol-induced oxidative stress impairs HIF-1α function, leading to reduced PFKP transcription, decreased glycolysis, and impaired phagocytosis; mitoquinol (MitoQ) restores HIF-1α function and PFKP expression. ChIP-qPCR for HIF-1α binding to PFKP promoter, macrophage ethanol exposure, PFKP mRNA/protein measurement, glycolysis assays, phagocytosis assays, MitoQ treatment, in vivo sepsis survival Journal of immunology High 40356076
2025 TRIS(2-chloroethyl)phosphate (TCEP) decreases PFKP glycolytic activity by enhancing O-linked N-acetylglucosamine (O-GlcNAc) transferase interaction with PFKP, thereby impairing glycolysis and ATP production in platelets, leading to suppression of platelet aggregation and activation. Proteomic analysis of platelets, O-GlcNAc transferase-PFKP interaction assay, PFKP activity assay, glycolysis/PPP pathway assays, ATP measurement, platelet activation assays, in vivo model Environmental pollution Medium 39828204
2025 Stat1 transcriptionally regulates Pfkp expression in macrophages; dsHMGB1 activates the Jak2/Stat1 pathway, which upregulates Pfkp to promote glycolysis and M1 macrophage polarization. ChIP-qPCR and dual-luciferase assays confirmed Stat1 binding to the Pfkp promoter. ChIP-qPCR, dual-luciferase assay, Jak2/Stat1 pathway inhibitor (fludarabine), dsHMGB1 treatment, glycolysis assays, macrophage polarization assays International journal of biological sciences Medium 41079919
2026 ATM kinase phosphorylates PFKP at threonine 278 (T278) in response to ionizing radiation and high glucose, promoting PFKP transition from tetramers to dimers; nuclear dimeric PFKP recruits casein kinase 2 (CK2), which phosphorylates RAD51 at T13 to enhance RAD51-BRCA2 interaction and homologous recombination (HR) repair. In vitro phosphorylation assay (ATM kinase), phosphosite mutagenesis (T278), PFKP tetramer/dimer structural analysis, nuclear fractionation, CK2 recruitment Co-IP, RAD51 T13 phosphorylation assay, HR repair assay, irradiation and high glucose conditions Nucleic acids research High 42011782
2026 PFKP directly binds AMOTL1 and inhibits its ubiquitin-mediated degradation; PFKP-driven aerobic glycolysis and EMT in HNSCC are AMOTL1-dependent. PFKP promotes YAP nuclear translocation via AMOTL1, suppressing Hippo pathway activity and amplifying glycolytic flux. Co-immunoprecipitation, ubiquitination analysis, AMOTL1 knockdown rescue, YAP nuclear translocation assays, Hippo pathway readouts, in vivo nude mice tumor models Journal of translational internal medicine Medium 41727965
2026 USP14 deubiquitinase stabilizes PFKP through K48-linked deubiquitination; c-Myc transcriptionally upregulates USP14, while PFKP enhances ERK-dependent c-Myc protein stability, forming a c-Myc-USP14-PFKP feed-forward regulatory circuit that sustains PDAC chemoresistance. Ubiquitination assays (K48-linked), USP14-PFKP protein interaction studies, c-Myc transcriptional activation of USP14, ERK-c-Myc stability assays, patient-derived organoids, syngeneic and xenograft models, combined targeting experiments Drug resistance updates Medium 41812332
2026 PFKP K688 lactylation (K688la) is induced by hypoxia/ischemia and enhances PFKP enzymatic activity (distinct from K688 lactylation inhibiting activity in cancer cells [PMID 38155775]); a K688E mutation mimicking hyper-lactylation further amplifies glycolysis and confers cardiomyocyte cytoprotection. Lactylome proteomics (LAD-operated mice, hypoxic cardiomyocytes), PFKP K688E mutagenesis, PFKP enzymatic activity assays, ECAR/OCR metabolic assays, cardiomyocyte survival assays, 2-DG rescue Frontiers in pharmacology Medium 41919225

Source papers

Stage 0 corpus · 57 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 256 33434505
2017 Snail reprograms glucose metabolism by repressing phosphofructokinase PFKP allowing cancer cell survival under metabolic stress. Nature communications 147 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 96 21586797
2020 PFKP is highly expressed in lung cancer and regulates glucose metabolism. Cellular oncology (Dordrecht, Netherlands) 83 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 73 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 59 30250190
2019 PFKP Signaling at a Glance: An Emerging Mediator of Cancer Cell Metabolism. Advances in experimental medicine and biology 55 30919341
2023 Proteomic analysis identifies PFKP lactylation in SW480 colon cancer cells. iScience 51 38155775
2023 Inhibition of PFKP in renal tubular epithelial cell restrains TGF-β induced glycolysis and renal fibrosis. Cell death & disease 46 38086793
2021 Cistrome analysis of YY1 uncovers a regulatory axis of YY1:BRD2/4-PFKP during tumorigenesis of advanced prostate cancer. Nucleic acids research 45 33849067
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 44 31904363
2021 Nuclear PFKP promotes CXCR4-dependent infiltration by T cell acute lymphoblastic leukemia. The Journal of clinical investigation 43 34255748
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
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 33 33588886
2023 p53-responsive CMBL reprograms glucose metabolism and suppresses cancer development by destabilizing phosphofructokinase PFKP. Cell reports 32 37967006
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 31 34367973
2024 A positive feedback loop between PFKP and c-Myc drives head and neck squamous cell carcinoma progression. Molecular cancer 28 38982480
2024 PFKP deubiquitination and stabilization by USP5 activate aerobic glycolysis to promote triple-negative breast cancer progression. Breast cancer research : BCR 25 38217030
2019 Mutant IDH1 confers resistance to energy stress in normal biliary cells through PFKP-induced aerobic glycolysis and AMPK activation. Scientific reports 25 31827136
2021 Silencing PFKP restrains the stemness of hepatocellular carcinoma cells. Experimental cell research 23 34418458
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 20 37326348
2023 SIRT2-PFKP interaction dysregulates phagocytosis in macrophages with acute ethanol-exposure. Frontiers in immunology 19 36865524
2022 PFKP Activation Ameliorates Foot Process Fusion in Podocytes in Diabetic Kidney Disease. Frontiers in endocrinology 16 35095764
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 15 36792847
2023 PFKP: More than phosphofructokinase. Advances in cancer research 15 37704285
2021 Triptolide impairs glycolysis by suppressing GATA4/Sp1/PFKP signaling axis in mouse Sertoli cells. Toxicology and applied pharmacology 15 34087332
2023 PFKP confers chemoresistance by upregulating ABCC2 transporter in non-small cell lung cancer. Translational lung cancer research 12 38090515
2024 PFKP Lactylation Promotes the Ovarian Cancer Progression Through Targeting PTEN. Biochemical genetics 11 39638933
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
2021 PFKP facilitates ATG4B phosphorylation during amino acid deprivation-induced autophagy. Cellular signalling 10 33607258
2023 Glycolytic Pfkp acts as a Lin41 protein kinase to promote endodermal differentiation of embryonic stem cells. EMBO reports 8 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 P4HA2 promotes the progression of thyroid cancer by regulating PFKP-mediated glycolysis. Journal of physiology and biochemistry 1 40762768
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
2026 Isoliquiritigenin Impedes Breast Cancer Progression through PITX1-PFKP-Mediated Glycolysis Reprogramming. Oncology research 0 42065039
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 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

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