Affinage

ENO1

Alpha-enolase · UniProt P06733

Length
434 aa
Mass
47.2 kDa
Annotated
2026-04-28
100 papers in source corpus 32 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ENO1 is a multifunctional glycolytic enzyme that also operates as a cell-surface plasminogen receptor, an RNA-binding post-transcriptional regulator, and—through its alternatively translated product MBP-1—a sequence-specific transcriptional repressor. As an enolase, it catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate; its enzymatic activity is enhanced by PRMT5- and PRMT6-mediated arginine methylation at R9 (promoting homodimerization) and R372 (promoting substrate binding), and by CBP-mediated crotonylation at K420 (reversed by SIRT2), while protein stability is controlled by FBXW7-directed ubiquitin-proteasomal degradation countered by deubiquitinases USP46 and USP21 (PMID:17, PMID:20, PMID:18, PMID:34335983, PMID:32707136, PMID:38385089). ENO1 binds plasminogen via its C-terminal lysine to enhance plasminogen activation on the cell surface, interacts with HGFR to activate Wnt/β-catenin signaling and EMT, and functions as an RNA-binding protein that recruits the deadenylase CNOT6 to degrade IRP1 mRNA (suppressing ferroptosis), promotes YAP1 translation by binding CUG-rich elements, and stabilizes KLF2 and FUS mRNAs to inhibit NLRP3-mediated pyroptosis (PMID:9003434, PMID:34145039, PMID:35121990, PMID:37500770, PMID:39467260). MBP-1, an N-terminally truncated ENO1 isoform containing a Cys2His2 zinc-finger domain, represses transcription at the c-myc P2 and COX-2 promoters and regulates cell-cycle progression and senescence; its translation is modulated by the AKT/PERK/eIF2α axis and by miR-363-mediated targeting of the shared 3′-UTR (PMID:1567844, PMID:9074493, PMID:19846662, PMID:16762917, PMID:20412594, PMID:23975832).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1992 High

    Determining how the MBP-1 isoform recognizes DNA established the structural basis for ENO1's moonlighting transcriptional repressor function: NMR revealed a double Cys2His2 zinc-finger fold that contacts ~10 bp of the c-myc P2 promoter, distinct from canonical zinc-finger orientations.

    Evidence NMR solution structure with 1280 restraints and 30 simulated-annealing structures

    PMID:1567844

    Open questions at the time
    • No co-crystal with DNA; exact base contacts inferred rather than directly visualized
    • Whether the zinc-finger fold is functional in the context of full-length ENO1 (vs. MBP-1 alone) was unresolved
  2. 1997 High

    Three parallel studies resolved ENO1's dual moonlighting identity—as a plasminogen receptor and a transcriptional repressor with separable functional domains: the C-terminal lysine mediates plasminogen binding (~1.9 µM Kd), the N-terminal half of MBP-1 binds c-myc P2 to repress transcription, and the C-terminal half of MBP-1 independently induces cell death.

    Evidence Recombinant protein binding assays with carboxypeptidase B treatment; deletion mutagenesis with reporter and colony-formation assays; HIV-1 LTR reporter system

    PMID:9003434 PMID:9074493 PMID:9093905

    Open questions at the time
    • Cell-surface display mechanism of ENO1 (lacking a signal peptide) was unexplained
    • No in vivo validation of plasminogen-receptor function at this stage
  3. 2006 High

    Endogenous MBP-1 was shown to be required for normal cell-cycle progression and proliferative homeostasis: MBP-1 knockdown caused G2/M arrest with cyclin A/B1 loss in cancer cells and premature senescence with p53/p21 activation in primary fibroblasts, rescuable by MBP-1 re-expression.

    Evidence Stable shRNA knockdown with FACS analysis, Western blot, and add-back rescue in PC3 cells and primary fibroblasts

    PMID:16762917 PMID:18852884

    Open questions at the time
    • Whether MBP-1 regulates cell cycle through direct transcriptional targets beyond c-myc was unclear
    • Relative contributions of ENO1 enzymatic vs. MBP-1 transcriptional functions not separated in knockdown experiments
  4. 2009 Medium

    MBP-1's transcriptional repressor repertoire was expanded beyond c-myc: MBP-1 directly binds the COX-2 promoter, and COX-2 suppression mediates MBP-1's anti-proliferative and anti-invasive effects in gastric cancer.

    Evidence Promoter binding assay, MBP-1 overexpression/knockdown, xenograft model

    PMID:19846662

    Open questions at the time
    • Genome-wide identification of MBP-1 target promoters was lacking
    • Whether MBP-1 zinc-finger domain contacts the COX-2 promoter directly was not structurally confirmed
  5. 2010 Medium

    Hypoxia was found to differentially regulate MBP-1 vs. full-length ENO1 translation, resolving how tumors co-opt the ENO1 locus: the AKT/PERK/eIF2α axis attenuates MBP-1 translation under hypoxia, de-repressing c-myc and promoting aerobic glycolysis, while stress conditions can also activate cap-independent MBP-1 translation.

    Evidence ChIP for MBP-1 on c-myc promoter under hypoxia; pathway inhibitor studies in multiple cell lines

    PMID:20412594 PMID:26144282

    Open questions at the time
    • The IRES or cap-independent element in ENO1 mRNA was not mapped
    • Context-dependent switching between MBP-1 suppression and induction not fully resolved
  6. 2012 High

    ENO1's cell-surface plasminogen-receptor function was validated in a paracrine cancer context: estradiol-stimulated stromal cells secrete ENO1, which binds prostate cancer cell surfaces to promote migration, establishing a non-cell-autonomous role for ENO1 in the tumor microenvironment.

    Evidence Mass spectrometry identification, immunodepletion, recombinant ENO1 rescue, conditioned-medium migration assay

    PMID:22734040

    Open questions at the time
    • Secretion mechanism for cytosolic ENO1 remains unexplained
    • Whether paracrine ENO1 signals through plasminogen activation or a distinct receptor was not fully resolved
  7. 2015 Medium

    The ubiquitin-proteasome pathway was identified as a major regulator of ENO1 protein levels: FBXW7 directly binds and ubiquitinates ENO1 for degradation, controlling downstream glycolysis, proliferation, and migration.

    Evidence Co-IP, 2D-electrophoresis/MS, ubiquitination assay, siRNA knockdown in colorectal cancer cells

    PMID:26097998

    Open questions at the time
    • FBXW7 degron motif in ENO1 was not mapped
    • Whether FBXW7 targets ENO1 and MBP-1 equally was not addressed
  8. 2018 Medium

    WBP2 was identified as a direct ENO1-interacting protein that modulates ENO1 glycolytic activity and downstream PI3K/AKT signaling, indicating that ENO1 enzymatic output is subject to protein-protein regulation beyond post-translational modification.

    Evidence MS/GST pulldown, Co-IP, siRNA epistasis, in vitro and in vivo glioma models

    PMID:29497031

    Open questions at the time
    • Mechanism by which WBP2 enhances ENO1 activity (allosteric vs. stabilization) was not determined
    • Single lab finding
  9. 2020 Medium

    USP46 was identified as a deubiquitinase that stabilizes ENO1, establishing the first DUB-mediated counter-regulation of ENO1 degradation and linking ENO1 stability to EMT and metastasis.

    Evidence Co-IP, ubiquitination assay, USP46 knockdown/overexpression, in vivo metastasis model in esophageal cancer

    PMID:32707136

    Open questions at the time
    • Whether USP46 opposes FBXW7 specifically or other E3 ligases was not tested
    • Single lab finding
  10. 2021 High

    Multiple post-translational regulatory mechanisms for ENO1 enzymatic activity were resolved in parallel: PRMT6 methylates R9 and R372 to promote dimerization and substrate binding; CBP crotonylates K420 (reversed by SIRT2) to enhance activity; CCDC65 scaffolds FBXW7 to ENO1 to promote degradation; and cell-surface ENO1 activates HGFR–Wnt signaling to drive EMT.

    Evidence In vitro methylation with site mutagenesis and dimer assays; quantitative crotonylomics with writer/eraser identification; GST pulldown and ubiquitination with domain mapping; Co-IP of ENO1–HGFR with phosphorylation assays and in vivo models

    PMID:34145039 PMID:34335983 PMID:34547627 PMID:36815049

    Open questions at the time
    • Interplay between R9 methylation and K420 crotonylation on the same ENO1 molecule not examined
    • Whether HGFR activation requires ENO1 enzymatic activity or only surface binding was not dissected
  11. 2021 High

    ENO1's RNA-binding function was mechanistically established: ENO1 recruits the deadenylase CNOT6 to accelerate IRP1 mRNA decay, reducing IRP1 protein and mitoferrin-1 expression, thereby suppressing mitochondrial iron–induced ferroptosis in hepatocellular carcinoma.

    Evidence RIP, mRNA decay assay, CNOT6 Co-IP, ENO1 knockdown/overexpression in vitro and in vivo

    PMID:35121990

    Open questions at the time
    • RNA-binding domain of ENO1 not mapped
    • How ENO1 partitions between glycolytic and RNA-binding functions was unknown
  12. 2022 High

    Epitranscriptomic regulation of ENO1 mRNA was discovered: METTL3-mediated m6A at position 359A and YTHDF1 reading promote ENO1 translation, while PRMT5-mediated symmetric dimethylation at R9 provided an independent route to ENO1 activation through dimer stabilization.

    Evidence m6A site mapping, YTHDF1 RIP, METTL3 KO, translation assays in lung adenocarcinoma; in vitro methylation and dimer assays in ovarian cancer

    PMID:35078505 PMID:36999124

    Open questions at the time
    • Whether m6A and protein-level PTMs are coordinated in the same cellular context was not tested
    • Relative quantitative contribution of translational vs. post-translational regulation to ENO1 levels unknown
  13. 2023 High

    ENO1's RNA-binding repertoire was broadened to translational promotion and mRNA stabilization: ENO1 binds CUG-rich elements in YAP1 mRNA to promote its translation, driving arachidonic acid metabolism in HCC, and stabilizes KLF2 and FUS mRNAs (facilitated by circFndc3b) to suppress NLRP3-mediated pyroptosis.

    Evidence RIP, RNA pulldown, translation/stability assays, aspirin rescue, in vivo HCC and stroke models

    PMID:37500770 PMID:39467260

    Open questions at the time
    • Global RNA target landscape (CLIP-seq) for ENO1 has not been reported
    • Structural basis for CUG recognition by ENO1 unknown
  14. 2024 High

    Multilayered epitranscriptomic and protein-level control of ENO1 was further detailed: m5C modification by NSUN2/YBX1 enhances ENO1 expression with a lactylation-driven feedback loop; ac4C modification by NAT10 enhances ENO1 expression; USP21 deubiquitinates K48-linked chains on ENO1; LINC00520 shields ENO1 from FBXW7; IL1R2 directly inhibits ENO1 enzymatic activity to suppress glycolysis and pyroptosis; and CGA covalently inhibits ENO1.

    Evidence m5C-RIP and lactylation assays; ac4C-RIP with rescue; Co-IP and deubiquitination assays; lncRNA–ENO1 interaction and ubiquitination assays; IL1R2 KO mouse model with ENO1 inhibitor epistasis; ABPP with activity assays

    PMID:38385089 PMID:38769664 PMID:39168299 PMID:39741388 PMID:39948547 PMID:40704655

    Open questions at the time
    • Integration of multiple mRNA modifications (m6A, m5C, ac4C) on the same ENO1 transcript not examined
    • Physiological hierarchy among FBXW7, USP46, and USP21 in ENO1 turnover unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis for ENO1's RNA-binding activity and how it partitions between glycolytic, RNA-binding, plasminogen-receptor, and transcriptional-repressor functions in a single cell; the mechanism of ENO1 secretion and cell-surface display; and the global landscape of RNA targets and genomic promoter targets.
  • No CLIP-seq or genome-wide ChIP for MBP-1 reported
  • Secretion pathway for ENO1 (unconventional secretion) uncharacterized
  • No structural model for ENO1–RNA interaction

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016829 lyase activity 5 GO:0003723 RNA binding 4 GO:0140110 transcription regulator activity 4 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 3 GO:0005886 plasma membrane 3 GO:0005576 extracellular region 1
Pathway
R-HSA-1430728 Metabolism 6 R-HSA-392499 Metabolism of proteins 5 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-8953854 Metabolism of RNA 4 R-HSA-5357801 Programmed Cell Death 3 R-HSA-109582 Hemostasis 1

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 Recombinant human ENO1 protein binds plasminogen in a lysine-dependent manner (Kd ~1.9 µM); removal of the C-terminal lysine by carboxypeptidase B significantly reduces plasminogen binding. Binding to ENO1 enhances plasminogen activation by urokinase and prevents α2-antiplasmin from binding plasminogen. In vitro binding assay with recombinant protein, carboxypeptidase B treatment, inhibition by lysine analogues (ε-amino caproic acid, tranexamic acid) Biochimica et biophysica acta High 9003434
1992 The NMR solution structure of the double Cys2His2 zinc finger of MBP-1 (an alternative translation product of ENO1) was determined; each finger comprises an antiparallel sheet and helix with zinc tetrahedrally coordinated to two cysteines and two histidines. The relative orientation of the two fingers differs from Zif268, consistent with MBP-1 contacting 10 base pairs of the c-myc P2 promoter. NMR spectroscopy with 1280 experimental restraints; 30 simulated annealing structures calculated Biochemistry High 1567844
1997 The N-terminal half (amino acids 1–178) of MBP-1 (encoded by ENO1) contains the c-myc P2 promoter binding domain and acts as a transcriptional repressor in vitro, while the C-terminal half (amino acids 190–335) is sufficient to induce cell death in fibroblasts and suppress colony formation in breast carcinoma cells. DNA-protein interaction assay with deletion mutants, transient transfection reporter assay, colony formation assay Gene High 9074493
1997 MBP-1 (ENO1 alternative translation product) inhibits HIV-1 LTR-directed transcription through the core promoter; the C-terminal half of MBP-1 mediates this suppression. Exogenous MBP-1 expression suppresses HIV-1 replication in acutely infected cells. Transient cotransfection with CAT reporter constructs using deletion mutants of MBP-1 and HIV-1 LTR deletions; HIV-1 replication assay Journal of cellular biochemistry Medium 9093905
2006 Knockdown of endogenous MBP-1 (ENO1 alternative product) in prostate cancer cells (PC3) causes G2/M accumulation and reduces cyclin A and cyclin B1 expression; supplementation with exogenous MBP-1 restores cyclin levels, demonstrating that endogenous MBP-1 promotes cell cycle progression through G2/M. Stable shRNA knockdown, FACS cell-cycle analysis, Western blot for cyclins, MBP-1 add-back rescue The Journal of biological chemistry High 16762917
2008 Knockdown of endogenous MBP-1 in primary human foreskin fibroblasts induces premature senescence associated with G1 accumulation, increased cyclin D1, reduced cyclin A, elevated phosphorylated and acetylated p53, p21 upregulation, and increased PML bodies. RNA interference in primary human fibroblasts, FACS, Western blot, SA-β-galactosidase staining, PML body immunofluorescence PloS one Medium 18852884
2009 MBP-1 (ENO1 alternative product) binds the COX-2 promoter and transcriptionally downregulates COX-2 expression; MBP-1-mediated suppression of gastric cancer cell proliferation, migration, invasion, and xenograft growth is mediated through COX-2 inhibition. MBP-1 overexpression/knockdown, colony formation, migration/invasion assays, xenograft model, COX-2 promoter binding Molecular biology of the cell Medium 19846662
2010 Under hypoxia, MBP-1 translation from the ENO1 mRNA is attenuated via the AKT/PERK/eIF2α signaling axis, reducing MBP-1 binding to the c-myc P2 promoter and allowing c-myc upregulation to promote aerobic glycolysis. Chromatin immunoprecipitation for MBP-1 on c-myc promoter, hypoxia treatment with 1% O2, glucose concentration variation, Western blot for MBP-1 and signaling components BMC cancer Medium 20412594
2012 ENO1 is secreted from prostate stromal cells in response to estradiol (via estrogen receptor-α stabilization of ENO1 protein); secreted ENO1 binds to the surface of prostate cancer cells acting as a plasminogen receptor and promotes cancer cell migration in a paracrine manner. 2D protein electrophoresis, mass spectrometry, immunodepletion assay, estradiol stimulation, conditioned medium migration assay, recombinant ENO1 treatment Molecular endocrinology High 22734040
2013 miR-363 targets the 3′-UTR of the MBP-1/α-enolase mRNA, suppressing MBP-1 translation; this promotes gastric cancer cell proliferation, EMT, and tumor xenograft growth and lung metastasis, which is reversed by miR-363 knockdown via MBP-1 upregulation. Luciferase reporter assay for 3′-UTR targeting, miR-363 overexpression/knockdown, xenograft/metastasis model Carcinogenesis Medium 23975832
2015 FBXW7 physically binds ENO1 and targets it for ubiquitin-mediated proteasomal degradation; FBXW7 depletion increases ENO1 protein levels and downstream lactate production, proliferation, and migration in colorectal cancer cells. Co-immunoprecipitation, 2D electrophoresis-mass spectrometry, Western blot, ubiquitination assay, siRNA knockdown Laboratory investigation Medium 26097998
2015 Under cellular stress, MBP-1 (ENO1 alternative product) is translated by a cap-independent mechanism driven by the AKT/PERK/eIF2α signaling axis. Western blot analysis of MBP-1 under cellular stress conditions with pathway inhibitors in SkBr3 and HEK293T cells FEBS letters Medium 26144282
2018 WBP2 directly interacts with ENO1 (identified by MS/GST pulldown); WBP2 modulates ENO1 glycolytic activity and downstream PI3K/Akt signaling to promote glioma cell proliferation and migration; ENO1 knockdown reverses WBP2-induced oncogenic effects. MS/GST pulldown assay, Co-IP, siRNA knockdown, in vitro and in vivo proliferation/migration assays Cell death & disease Medium 29497031
2020 USP46 is a deubiquitinating enzyme that stabilizes ENO1 protein through deubiquitination, promoting esophageal cancer cell migration and invasion via EMT. Co-immunoprecipitation, ubiquitination assay, USP46 knockdown/overexpression with ENO1 protein level measurement, in vivo metastasis model Experimental cell research Medium 32707136
2021 ENO1 functions as an RNA-binding protein that recruits the deadenylase CNOT6 to accelerate IRP1 mRNA decay in hepatocellular carcinoma cells, leading to reduced IRP1 protein, decreased mitoferrin-1 (Mfrn1) expression, and suppression of mitochondrial iron-induced ferroptosis. RNA immunoprecipitation (RIP), mRNA decay assay, CNOT6 Co-IP, in vitro and in vivo functional assays with ENO1 knockdown/overexpression Nature cancer High 35121990
2021 ENO1 interacts with hepatocyte growth factor receptor (HGFR) on the cell surface, activating HGFR and Wnt signaling through increased phosphorylation of HGFR and LRP5/6; this leads to Src-PI3K-AKT-mediated GSK3β inactivation, stabilization of β-catenin and SLUG, and promotion of EMT and lung cancer metastasis. Co-immunoprecipitation, phosphorylation assays, overexpression/knockdown, anti-ENO1 antibody treatment, orthotopic and tail-vein mouse models Cancer research High 34145039
2021 CCDC65 binds ENO1 via its 130–484 aa domain and recruits E3 ubiquitin ligase FBXW7 to promote ENO1 ubiquitylation and proteasomal degradation; reduced ENO1 decreases AKT1 binding and AKT1 activation, suppressing gastric cancer proliferation and EMT. Co-immunoprecipitation, GST pulldown, ubiquitination assay, domain deletion mapping, in vitro and in vivo functional assays Theranostics High 34335983
2021 PRMT6 methylates ENO1 at R9 (promoting active dimer formation) and R372 (promoting 2-phosphoglycerate substrate binding), enhancing ENO1 enzymatic activity and glycolytic flux in lung cancer cells. In vitro methylation assay, site-directed mutagenesis (R9 and R372), glycolysis flux measurement, dimer formation assay Acta pharmaceutica Sinica. B High 36815049
2021 CBP (CREB-binding protein) functions as a crotonyltransferase that crotonylates ENO1 at lysine K420, while SIRT2 acts as the decrotonylase; ENO1 K420 crotonylation enhances ENO1 enzymatic activity and promotes colorectal cancer cell growth, migration, and invasion. Quantitative mass spectrometry for crotonylomics, site identification, in vitro assays with K420 mutant ENO1, SIRT2/CBP manipulation Biochemical and biophysical research communications High 34547627
2022 m6A methylation of ENO1 mRNA at position 359A by METTL3 facilitates binding by the m6A reader YTHDF1, resulting in enhanced ENO1 translation and increased glycolysis in lung adenocarcinoma cells. m6A site mapping, YTHDF1 RIP assay, METTL3/ALKBH5 knockout, translation assay, in vivo tumor formation Journal of experimental & clinical cancer research High 35078505
2022 PRMT5 symmetrically dimethylates ENO1 at arginine 9, promoting active ENO1 dimer formation and increased glycolytic flux in ovarian cancer cells; PRMT5 inhibition reduces ENO1 dimerization and glycolysis. In vitro methylation assay, R9 site-directed mutagenesis, dimer formation assay, glycolysis measurement, PRMT5 knockdown/inhibition MedComm High 36999124
2023 ENO1, as an RNA-binding protein, binds CUG-rich elements in YAP1 mRNA 3′ region to promote YAP1 translation; ENO1/YAP1 together upregulate PLCB1 and downregulate HPGD, activating arachidonic acid metabolism and PGE2 accumulation to drive hepatocellular carcinoma progression. RNA immunoprecipitation (RIP), RNA pull-down, YAP1 translation assay, PLCB1/HPGD expression analysis, aspirin rescue experiment, in vitro and in vivo HCC models Nature chemical biology High 37500770
2023 ENO1 upregulates PD-L1 expression through the HIF-1α signaling pathway in pancreatic cancer cells, reducing CD8+ T cell infiltration and promoting immune evasion. ENO1 knockdown (siRNA/CRISPR), flow cytometry for CD8+ T cells, PD-L1 Western blot, HIF-1α pathway analysis, in vivo pancreatic cancer model Translational oncology Medium 39752908
2023 ENO1, as an RNA-binding protein, binds the 3′-UTR of KLF2 mRNA to stabilize it, increasing KLF2 protein expression and suppressing NLRP3 inflammasome-mediated microglial pyroptosis; circFndc3b interaction with ENO1 facilitates ENO1's binding to KLF2 and FUS mRNAs. RNA immunoprecipitation (RIP), RNA pulldown, mRNA stability assay, Co-IP for circFndc3b-ENO1 interaction, in vitro pyroptosis assay, in vivo stroke model Advanced science Medium 39467260
2023 IL1R2 physically interacts with ENO1 in macrophages and suppresses ENO1 enzymatic activity, thereby inhibiting glycolysis and GSDMD-mediated pyroptosis; IL1R2-deficient mice show heightened sepsis severity that is rescued by ENO1 inhibition. Proteomic screening, Co-immunoprecipitation of IL1R2-ENO1, ENO1 activity assay, IL1R2 KO mouse model, ENO1 inhibitor treatment in sepsis Advanced science High 40704655
2024 NSUN2 (m5C methyltransferase) and YBX1 (m5C reader) cooperate to methylate ENO1 mRNA at m5C sites, enhancing ENO1 expression and glucose metabolism in colorectal cancer; lactate produced downstream activates H3K18 lactylation of NSUN2 promoter and K356 lactylation of NSUN2 protein, forming a positive feedback loop. RNA m5C methylation assay, RIP for NSUN2 and YBX1, m5C site mapping, NSUN2/YBX1 knockdown, glycolysis measurement, lactylation analysis Advanced science High 38769664
2024 USP21 directly deubiquitinates (K48-linked) and stabilizes ENO1 protein in cholangiocarcinoma cells, promoting glycolysis and cell proliferation. Co-immunoprecipitation, deubiquitination assay (K48-linked ubiquitin), USP21 knockdown, ENO1 protein stability measurement International journal of biological sciences Medium 38385089
2024 RBM15/METTL3 complex enhances m6A modification of ENO1 mRNA at the 359A site in bladder cancer cells; YTHDF1 reads this modification and promotes ENO1 protein translation. TGF-β activates RBM15/METTL3 via Smad2/3. ENO1 then stabilizes PCNA by reducing K48-linked ubiquitination, preventing PCNA degradation. m6A-RIP, RBM15/METTL3 Co-IP, site-specific m6A mapping (359A), YTHDF1 RIP, PCNA ubiquitination assay, in vitro and in vivo proliferation assays Cancer letters High 38823761
2024 ENO1 acts as an RNA-binding protein that binds the 3′-UTR of KLF2 and FUS mRNAs; in the context of circFndc3b interaction, ENO1 stabilizes these mRNAs to suppress NLRP3-mediated pyroptosis and promote FUS-driven circFndc3b cyclization. RIP, RNA pulldown, mRNA stability assay with circFndc3b-ENO1 interaction mapping Advanced science Medium 39467260
2024 NAT10 acetylates ENO1 mRNA via ac4C modification, enhancing ENO1 expression; NAT10 knockdown reduces ac4C on ENO1 mRNA, suppresses glycolysis and promotes apoptosis in NSCLC cells, effects reversed by ENO1 overexpression. ac4C-RNA immunoprecipitation, NAT10 knockdown, ENO1 overexpression rescue, glycolysis measurement, apoptosis assay BMC pulmonary medicine Medium 39948547
2024 LINC00520 binds ENO1 protein and blocks FBXW7-mediated ubiquitination and proteasomal degradation of ENO1, thereby stabilizing ENO1 protein and promoting glycolysis and cisplatin resistance in osteosarcoma; METTL3 stabilizes LINC00520 via m6A-YTHDF2. Co-immunoprecipitation of LINC00520-ENO1, ubiquitination assay, FBXW7 interaction assay, in vitro and in vivo chemoresistance assays Cancer letters Medium 39168299
2024 ENO1 silencing in disturbed-flow-exposed endothelial cells represses TGF-β-induced endothelial-to-mesenchymal transition (EndMT) and inflammation; ENO1 is highly expressed at the inner curvature of mouse aortic arch exposed to disturbed shear and in atherosclerotic lesions, placing ENO1 downstream of disturbed shear/TGF-β in the EndMT pathway. Single-cell RNA sequencing, pseudotime trajectory analysis, ENO1 siRNA knockdown in endothelial cells, in vivo aortic arch expression analysis Proceedings of the National Academy of Sciences of the United States of America Medium 38261622
2024 CGA (chlorogenic acid) covalently binds ENO1 protein (identified by activity-based protein profiling, ABPP) and suppresses ENO1 enzymatic activity, blocking glycolysis and preventing UVA-induced cellular senescence in skin fibroblasts. ABPP target identification, covalent binding validation, ENO1 activity assay, glycolysis measurement, UVA senescence model Aging cell Medium 39741388

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 F. nucleatum targets lncRNA ENO1-IT1 to promote glycolysis and oncogenesis in colorectal cancer. Gut 222 33318144
2021 ENO1 suppresses cancer cell ferroptosis by degrading the mRNA of iron regulatory protein 1. Nature cancer 167 35121990
2022 ENO1 and Cancer. Molecular therapy oncolytics 150 35434271
2024 Metabolic Recoding of NSUN2-Mediated m5C Modification Promotes the Progression of Colorectal Cancer via the NSUN2/YBX1/m5C-ENO1 Positive Feedback Loop. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 138 38769664
2021 ENO1 Promotes Lung Cancer Metastasis via HGFR and WNT Signaling-Driven Epithelial-to-Mesenchymal Transition. Cancer research 118 34145039
2013 Vaccination with ENO1 DNA prolongs survival of genetically engineered mice with pancreatic cancer. Gastroenterology 110 23333712
2022 The essential roles of m6A RNA modification to stimulate ENO1-dependent glycolysis and tumorigenesis in lung adenocarcinoma. Journal of experimental & clinical cancer research : CR 98 35078505
2017 Alpha-Enolase (ENO1), a potential target in novel immunotherapies. Frontiers in bioscience (Landmark edition) 84 27814656
2021 C5aR1-positive neutrophils promote breast cancer glycolysis through WTAP-dependent m6A methylation of ENO1. Cell death & disease 83 34312368
1987 Transcription of the constitutively expressed yeast enolase gene ENO1 is mediated by positive and negative cis-acting regulatory sequences. Molecular and cellular biology 79 3313003
2009 Molecular and functional characterization of the plastid-localized Phosphoenolpyruvate enolase (ENO1) from Arabidopsis thaliana. FEBS letters 73 19223001
2010 Hypoxia induces differential translation of enolase/MBP-1. BMC cancer 72 20412594
2023 ENO1 promotes liver carcinogenesis through YAP1-dependent arachidonic acid metabolism. Nature chemical biology 66 37500770
2015 FBXW7 negatively regulates ENO1 expression and function in colorectal cancer. Laboratory investigation; a journal of technical methods and pathology 64 26097998
2020 An enolase inhibitor for the targeted treatment of ENO1-deleted cancers. Nature metabolism 63 33230295
2022 PRMT6 promotes tumorigenicity and cisplatin response of lung cancer through triggering 6PGD/ENO1 mediated cell metabolism. Acta pharmaceutica Sinica. B 59 36815049
2005 Introduction of in vitro transcribed ENO1 mRNA into neuroblastoma cells induces cell death. BMC cancer 57 16359544
2015 ENO1 promotes tumor proliferation and cell adhesion mediated drug resistance (CAM-DR) in Non-Hodgkin's Lymphomas. Experimental cell research 54 26024773
1992 High-resolution solution structure of the double Cys2His2 zinc finger from the human enhancer binding protein MBP-1. Biochemistry 54 1567844
2018 WW domain-binding protein 2 acts as an oncogene by modulating the activity of the glycolytic enzyme ENO1 in glioma. Cell death & disease 53 29497031
2023 Targeting Endothelial ENO1 (Alpha-Enolase) -PI3K-Akt-mTOR Axis Alleviates Hypoxic Pulmonary Hypertension. Hypertension (Dallas, Tex. : 1979) 51 37075135
2021 CCDC65 as a new potential tumor suppressor induced by metformin inhibits activation of AKT1 via ubiquitination of ENO1 in gastric cancer. Theranostics 51 34335983
2014 Identification of ENO1 as a potential sputum biomarker for early-stage lung cancer by shotgun proteomics. Clinical lung cancer 49 24984566
2012 Estrogen promotes prostate cancer cell migration via paracrine release of ENO1 from stromal cells. Molecular endocrinology (Baltimore, Md.) 48 22734040
1997 The human ENO1 gene product (recombinant human alpha-enolase) displays characteristics required for a plasminogen binding protein. Biochimica et biophysica acta 48 9003434
2021 Upregulation of α enolase (ENO1) crotonylation in colorectal cancer and its promoting effect on cancer cell metastasis. Biochemical and biophysical research communications 45 34547627
2018 ENO1 Overexpression in Pancreatic Cancer Patients and Its Clinical and Diagnostic Significance. Gastroenterology research and practice 44 29483925
2013 Downregulation of tumor suppressor MBP-1 by microRNA-363 in gastric carcinogenesis. Carcinogenesis 44 23975832
2020 Preclinical validation of Alpha-Enolase (ENO1) as a novel immunometabolic target in multiple myeloma. Oncogene 42 32024967
2009 MBP-1 suppresses growth and metastasis of gastric cancer cells through COX-2. Molecular biology of the cell 41 19846662
2020 FGFRL1 affects chemoresistance of small-cell lung cancer by modulating the PI3K/Akt pathway via ENO1. Journal of cellular and molecular medicine 40 31957179
2019 Hyperglycemia promotes Snail-induced epithelial-mesenchymal transition of gastric cancer via activating ENO1 expression. Cancer cell international 40 31889896
2021 KMT5A downregulation participated in High Glucose-mediated EndMT via Upregulation of ENO1 Expression in Diabetic Nephropathy. International journal of biological sciences 38 34803485
2024 Single-cell RNA sequencing unveils unique transcriptomic signatures of endothelial cells and role of ENO1 in response to disturbed flow. Proceedings of the National Academy of Sciences of the United States of America 35 38261622
2022 Circular RNA circNFKB1 promotes osteoarthritis progression through interacting with ENO1 and sustaining NF-κB signaling. Cell death & disease 33 35945200
2022 Baicalein Acts against Candida albicans by Targeting Eno1 and Inhibiting Glycolysis. Microbiology spectrum 30 35900099
2023 Melatonin inhibits bladder tumorigenesis by suppressing PPARγ/ENO1-mediated glycolysis. Cell death & disease 29 37024456
2019 Up-regulated ENO1 promotes the bladder cancer cell growth and proliferation via regulating β-catenin. Bioscience reports 28 31431517
2022 FAM126A interacted with ENO1 mediates proliferation and metastasis in pancreatic cancer via PI3K/AKT signaling pathway. Cell death discovery 27 35513377
2024 METTL3-mediated m6A modification of LINC00520 confers glycolysis and chemoresistance in osteosarcoma via suppressing ubiquitination of ENO1. Cancer letters 25 39168299
2023 PRMT5 promotes ovarian cancer growth through enhancing Warburg effect by methylating ENO1. MedComm 25 36999124
2006 Tumor-suppressive effects of MBP-1 in non-small cell lung cancer cells. Cancer research 25 17178888
2020 CircZNF609 aggravates neuropathic pain via miR-22-3p/ENO1 axis in CCI rat models. Gene 24 32827683
2024 USP21 deubiquitinates and stabilizes HSP90 and ENO1 to promote aerobic glycolysis and proliferation in cholangiocarcinoma. International journal of biological sciences 23 38385089
2021 Salidroside Induces Apoptosis in Human Gastric Cancer Cells via the Downregulation of ENO1/PKM2/GLUT1 Expression. Biological & pharmaceutical bulletin 23 34471002
2020 Silencing of ENO1 inhibits the proliferation, migration and invasion of human breast cancer cells. Journal of B.U.ON. : official journal of the Balkan Union of Oncology 23 32521855
2014 Effects of skin-to-skin contact and breastfeeding at birth on the incidence of PPH: A physiologically based theory. Women and birth : journal of the Australian College of Midwives 23 25113818
2024 Role of ENO1 and its targeted therapy in tumors. Journal of translational medicine 22 39543641
2020 Ubiquitin-specific peptidase 46 promotes tumor metastasis through stabilizing ENO1 in human esophageal squamous cell carcinoma. Experimental cell research 22 32707136
1993 Linkage relationships between ALPL, ENO1, GPI, PGD, and TGFB1 on porcine chromosome 6. Genomics 22 8104872
2023 N6-methyladenosine methyltransferase KIAA1429 promoted ovarian cancer aerobic glycolysis and progression through enhancing ENO1 expression. Biology direct 21 37807062
2020 Cinnamaldehyde Enhances Antimelanoma Activity through Covalently Binding ENO1 and Exhibits a Promoting Effect with Dacarbazine. Cancers 21 32013122
2023 ENO1 Promotes OSCC Migration and Invasion by Orchestrating IL-6 Secretion from Macrophages via a Positive Feedback Loop. International journal of molecular sciences 20 36614179
2021 Alpha-enolase (ENO1), identified as an antigen to monoclonal antibody 12C7, promotes the self-renewal and malignant phenotype of lung cancer stem cells by AMPK/mTOR pathway. Stem cell research & therapy 20 33579362
2018 Silencing of ENO1 by shRNA Inhibits the Proliferation of Gastric Cancer Cells. Technology in cancer research & treatment 20 29986635
2016 Up-Regulation of ENO1 by HIF-1α in Retinal Pigment Epithelial Cells after Hypoxic Challenge Is Not Involved in the Regulation of VEGF Secretion. PloS one 20 26882120
2015 Cellular stress induces cap-independent alpha-enolase/MBP-1 translation. FEBS letters 20 26144282
2024 N6-Methyladenosine enhances the translation of ENO1 to promote the progression of bladder cancer by inhibiting PCNA ubiquitination. Cancer letters 19 38823761
2022 ENO1 contributes to 5-fluorouracil resistance in colorectal cancer cells via EMT pathway. Frontiers in oncology 19 36620599
1983 Chromosome localization of the genes for ENO1, HK1, ADK, ACP2, MPI, ITPA, ACON1 and α-GAL in the American mink (Mustela vison). TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 19 24258481
2024 CircFndc3b Mediates Exercise-Induced Neuroprotection by Mitigating Microglial/Macrophage Pyroptosis via the ENO1/KLF2 Axis in Stroke Mice. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 18 39467260
2023 Enhanced E6AP-mediated ubiquitination of ENO1 via LINC00663 contributes to radiosensitivity of breast cancer by regulating mitochondrial homeostasis. Cancer letters 18 36871813
2018 The Biological Significance and Regulatory Mechanism of c-Myc Binding Protein 1 (MBP-1). International journal of molecular sciences 18 30518090
2018 A new gold(I) complex-Au(PPh3)PT is a deubiquitinase inhibitor and inhibits tumor growth. EBioMedicine 18 30527624
2023 Beyond ENO1, emerging roles and targeting strategies of other enolases in cancers. Molecular therapy oncolytics 17 38075246
2020 The circ-AMOTL1/ENO1 Axis Implicated in the Tumorigenesis of OLP-Associated Oral Squamous Cell Carcinoma. Cancer management and research 17 32884340
2018 Identification of Piecemeal Degranulation and Vesicular Transport of MBP-1 in Liver-Infiltrating Mouse Eosinophils During Acute Experimental Schistosoma mansoni Infection. Frontiers in immunology 17 30619361
2023 Unrevealed roles of extracellular enolase‑1 (ENO1) in promoting glycolysis and pro‑cancer activities in multiple myeloma via hypoxia‑inducible factor 1α. Oncology reports 16 37800625
2022 TRPC5OS induces tumorigenesis by increasing ENO1-mediated glucose uptake in breast cancer. Translational oncology 16 35584604
2021 AL355338 acts as an oncogenic lncRNA by interacting with protein ENO1 to regulate EGFR/AKT pathway in NSCLC. Cancer cell international 16 34627260
2017 Peripartum Haemorrhage: Haemostatic Aspects of the New German PPH Guideline. Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie 16 29765296
2024 ENO1 deletion potentiates ferroptosis and decreases glycolysis in colorectal cancer cells via AKT/STAT3 signaling. Experimental and therapeutic medicine 15 38414789
2023 Knockout of ENO1 leads to metabolism reprogramming and tumor retardation in pancreatic cancer. Frontiers in oncology 15 36845730
2020 Gold Drugs with {Au(PPh3 )}+ Moiety: Advantages and Medicinal Applications. ChemMedChem 15 33025735
1997 Chromosomal localization of the human gene encoding c-myc promoter-binding protein (MPB1) to chromosome 1p35-pter. Genomics 15 9119380
2024 ENO1 contributes to the gemcitabine resistance of pancreatic cancer through the YAP1 signaling pathway. Molecular carcinogenesis 14 38517039
2021 EGR1 modulated LncRNA HNF1A-AS1 drives glioblastoma progression via miR-22-3p/ENO1 axis. Cell death discovery 14 34772911
2009 MBP-1 inhibits breast cancer growth and metastasis in immunocompetent mice. Cancer research 14 19934312
2007 Multiple basic helix-loop-helix proteins regulate expression of the ENO1 gene of Saccharomyces cerevisiae. Eukaryotic cell 14 17351075
2021 ENO1 monoclonal antibody inhibits invasion, proliferation and clone formation of cervical cancer cells. American journal of cancer research 13 34094663
2024 Marrow mesenchymal stem cell mediates diabetic nephropathy progression via modulation of Smad2/3/WTAP/m6A/ENO1 axis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 12 38847786
2022 Lactate promotes the growth of patient-derived organoids from hepatopancreatobiliary cancers via ENO1/HIF1α pathway and does not affect their drug sensitivities. Cell death discovery 12 35443744
2022 Linc-UROD stabilizes ENO1 and PKM to strengthen glycolysis, proliferation and migration of pancreatic cancer cells. Translational oncology 12 36413861
2006 Knockdown of MBP-1 in human prostate cancer cells delays cell cycle progression. The Journal of biological chemistry 12 16762917
2006 Metabolism of 2-, 3- and 4-hydroxybenzoates by soil isolates Alcaligenes sp. strain PPH and Pseudomonas sp. strain PPD. FEMS microbiology letters 12 17169001
1997 Separate domains of MBP-1 involved in c-myc promoter binding and growth suppressive activity. Gene 12 9074493
1997 Inhibition of human immunodeficiency virus type 1 replication by a cellular transcriptional factor MBP-1. Journal of cellular biochemistry 12 9093905
2024 ARNTL2 facilitates bladder cancer progression through potentiating ENO1-mediated glycolysis in a SLC31A1-independent and -dependent manner. Life sciences 11 39147318
2024 Kinetics and Mechanism of PPh3/Ni-Catalyzed, Zn-Mediated, Aryl Chloride Homocoupling: Antagonistic Effects of ZnCl2/Cl. Journal of the American Chemical Society 11 39420638
2023 ENO1 promotes immunosuppression and tumor growth in pancreatic cancer. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 11 36820953
2015 Effects of α-enolase (ENO1) over-expression on malignant biological behaviors of AGS cells. International journal of clinical and experimental medicine 11 25784992
2025 ENO1 promotes PDAC progression by inhibiting CD8+ T cell infiltration through upregulating PD-L1 expression via HIF-1α signaling. Translational oncology 10 39752908
2022 ENO1 Binds to ApoC3 and Impairs the Proliferation of T Cells via IL-8/STAT3 Pathway in OSCC. International journal of molecular sciences 10 36361568
2008 Knockdown of MBP-1 in human foreskin fibroblasts induces p53-p21 dependent senescence. PloS one 10 18852884
2025 Role of NAT10-mediated ac4C acetylation of ENO1 mRNA in glycolysis and apoptosis in non-small cell lung cancer cells. BMC pulmonary medicine 9 39948547
2024 Identifying ENO1 as a protein target of chlorogenic acid to inhibit cellular senescence and prevent skin photoaging in mice. Aging cell 9 39741388
2022 Alpha-Enolase (ENO1) Correlates with Invasiveness of Cutaneous Melanoma-An In Vitro and a Clinical Study. Diagnostics (Basel, Switzerland) 9 35204345
2019 Targetting an LncRNA P5848-ENO1 axis inhibits tumor growth in hepatocellular carcinoma. Bioscience reports 9 30541900
2019 Adipocyte abundances of CES1, CRYAB, ENO1 and GANAB are modified in-vitro by glucose restriction and are associated with cellular remodelling during weight regain. Adipocyte 9 31037987
2025 Critical Role of IL1R2-ENO1 Interaction in Inhibiting Glycolysis-Mediated Pyroptosis for Protection Against Lethal Sepsis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 8 40704655