Affinage

NME1

Nucleoside diphosphate kinase A · UniProt P15531

Length
152 aa
Mass
17.1 kDa
Annotated
2026-06-10
100 papers in source corpus 26 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NME1/NM23-H1 is a multifunctional metastasis suppressor whose anti-metastatic activity integrates several biochemically distinct enzymatic functions with control of cell motility and genome stability (PMID:20209495, PMID:17671192, PMID:18089805). Its founding biochemistry is nucleoside diphosphate kinase (NDPK) activity, transferring phosphate from ATP to nucleoside diphosphates via a phosphoenzyme intermediate (PMID:21584562), and during cytokinesis this provides a local GTP source for the GTPase dynamin, so that loss of NME1 causes furrow regression, cytokinesis failure, and tetraploidy (PMID:20713695). NME1 additionally possesses an intrinsic Mg2+-dependent 3'-5' exonuclease activity dependent on Lys12 that excises nucleotides from DNA 3' termini (PMID:14960567); this exonuclease, together with its kinase activity, supports repair of UV-induced (6-4) photoproducts and is specifically required for metastasis suppression in vivo, as exonuclease-dead E5A/K12Q mutants fail to suppress lung metastasis while retaining anti-motility activity in culture (PMID:20209495, PMID:22080566). NME1 also acts in the nucleus, binding and cleaving the C-rich strand of the PDGF-A promoter to repress transcription (PMID:11694515) and transcriptionally down-regulating the lysophosphatidic acid receptor EDG2/LPA1, an event functionally critical for suppressing motility and pulmonary metastatic colonization (PMID:17671192, PMID:18089805). At cell-cell contacts NME1 enforces contact inhibition of locomotion by associating with alpha-catenin and N-cadherin and inactivating Tiam1 to suppress Rac1 (PMID:22718351). It engages multiple partners including PRUNE/h-Prune (PMID:10602478, PMID:23448979), the p53 DNA-binding domain via STRAP to potentiate p53 activity by displacing Mdm2 (PMID:17916563), Cdc42 (PMID:19302816), and IRF6, where the cleft/lip-palate-associated R18Q mutation disrupts IRF6 binding and elevates Rac1/RhoA (PMID:28767310). Its enzymatic activities are redox-regulated: oxidation of Cys109 inhibits NDPK and metastasis-suppressor function with restoration by the TrxR1/thioredoxin system (PMID:19956735), while a Cys4-Cys145 intramolecular disulfide drives a conformational change dissociating the active hexamer into dimers (PMID:23519676). NME1 functions as a protein histidine kinase that autophosphorylates His118 and phosphorylates substrate proteins (PMID:32392889).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1992 High

    Established the core biochemical identity of NM23-H1 as a nucleoside diphosphate kinase, defining the enzymatic activity that frames all later mechanistic work.

    Evidence In vitro phosphoenzyme intermediate formation and TLC detection of GDP-to-GTP conversion with recombinant GST-fusion proteins

    PMID:21584562

    Open questions at the time
    • Does not connect NDPK activity to any cellular phenotype
    • Does not explain how a housekeeping kinase functions as a metastasis suppressor
  2. 1997 Medium

    Showed that reducing NM23-H1 directly inhibits proliferation, providing early evidence that NME1 participates in cell cycle progression rather than acting solely as a suppressor.

    Evidence Antisense oligonucleotide and stable antisense transfection in MCF10A cells with proliferation/S-phase readout

    PMID:9335458

    Open questions at the time
    • Antisense approaches lack target specificity controls
    • No molecular mechanism linking NM23-H1 to cell cycle machinery
  3. 1999 Medium

    Identified PRUNE as a physical partner of NM23-H1 and linked the metastasis-associated S120G mutant to loss of binding, opening the protein-interaction dimension of NME1 biology.

    Evidence Yeast two-hybrid interaction-mating, in vitro co-IP, confocal co-localization

    PMID:10602478

    Open questions at the time
    • Functional consequence of the interaction not established here
    • Binding interface not defined structurally
  4. 2001 High

    Demonstrated sequence-specific DNA binding/cleavage and transcriptional repression at the PDGF-A promoter, and localization to the centrosome with gamma-tubulin, extending NME1 beyond a soluble kinase.

    Evidence Recombinant DNA cleavage assays and HepG2 reporter assays; confocal imaging, centrosome purification, and co-IP with gamma-tubulin (rat ortholog)

    PMID:11139339 PMID:11694515

    Open questions at the time
    • Mechanism coupling DNA cleavage to repression unclear
    • Centrosomal role uses rat ortholog and lacks functional perturbation
  5. 2004 High

    Revealed an intrinsic 3'-5' exonuclease activity with a defined catalytic residue (Lys12), establishing a second enzymatic function distinct from NDPK.

    Evidence In vitro exonuclease assay with recombinant WT and K12Q mutant, co-purification, and active-site mutagenesis

    PMID:14960567

    Open questions at the time
    • In vivo substrate and biological role of the exonuclease undefined here
    • Relationship between exonuclease and NDPK active sites unresolved
  6. 2007 High

    Connected NME1 to a defined anti-motility/anti-metastatic effector pathway by showing transcriptional repression of EDG2/LPA1 is required to suppress motility and pulmonary metastatic colonization in vivo.

    Evidence Expression microarray, motility/rescue transfection, siRNA, spontaneous metastasis xenograft, and human breast tumor cohort IHC

    PMID:17671192 PMID:18089805

    Open questions at the time
    • Direct DNA-binding mechanism at the EDG2 promoter not shown
    • How NDPK/exonuclease activities relate to EDG2 repression unclear
  7. 2007 Medium

    Placed NME1 in the p53 axis by showing it binds the p53 DNA-binding domain via STRAP and potentiates p53 function by displacing Mdm2, linking metastasis suppression to tumor-suppressor signaling.

    Evidence Co-IP, domain/point-mutant mapping (NM23 Cys145, p53 Cys176), reporter assays, apoptosis/growth assays, siRNA

    PMID:17916563

    Open questions at the time
    • Single-lab interaction without reciprocal in vivo validation
    • Stoichiometry of the NM23/STRAP/p53 complex undefined
  8. 2009 High

    Defined a redox switch by mapping oxidative inhibition to Cys109 and identifying TrxR1 as the reductive restoration system, explaining how enzymatic and suppressor activities are controlled by oxidative stress.

    Evidence Tandem MS oxidation-site mapping, NDPK assays, TrxR1 co-IP and reduction assay, C109A mutagenesis, metastasis suppressor assay

    PMID:19956735

    Open questions at the time
    • Physiological triggers of oxidation in tumors not defined
    • Whether exonuclease/kinase activities share this regulation unaddressed
  9. 2010 High

    Established a genome-stability role by showing NME1 supplies local GTP to dynamin during cytokinesis, with its loss causing furrow regression and tetraploidy.

    Evidence RNAi, live-cell cytokinesis imaging, dynamin overexpression complementation, flow cytometry ploidy

    PMID:20713695

    Open questions at the time
    • Spatial mechanism of GTP channeling to dynamin not visualized directly
    • Contribution of this function to metastasis suppression not quantified
  10. 2010 Medium

    Broadened the partner network and downstream effects, linking NME1 to AP-1/p53 complexes and cyclin D1 repression, and to integrin beta1 glycosylation controlling adhesion/migration.

    Evidence Co-IP, cyclin D1 promoter reporter and apoptosis assays in B cells; adhesion/migration assays and integrin glycosylation analysis in hepatocarcinoma cells

    PMID:20448457 PMID:20618991

    Open questions at the time
    • Mechanistic basis of integrin glycosylation effect undefined
    • Single-lab co-IPs without reciprocal validation
  11. 2011 High

    Assigned the in vivo metastasis-suppressor requirement specifically to the 3'-5' exonuclease activity and tied NME1 to UV photoproduct repair, separating in vivo suppression from culture motility.

    Evidence E5A/K12Q mutagenesis with enzymatic and metastasis xenograft assays; NER kinetics, nuclear damage-site translocation imaging, and hemizygous-null mouse UV melanoma model

    PMID:20209495 PMID:22080566

    Open questions at the time
    • Direct in vivo DNA substrate of the exonuclease not identified
    • How exonuclease and kinase activities cooperate during repair unresolved
  12. 2011 Medium

    Showed NME1 subcellular localization is actively controlled, with KSHV LANA driving nuclear translocation that is required for Ras-BRaf-MAPK activation and invasion.

    Evidence Subcellular fractionation, confocal imaging, siRNA, ectopic LANA expression, MAPK/invasion assays, demethylation agent

    PMID:21270158

    Open questions at the time
    • Direct molecular trigger of LANA-mediated translocation undefined
    • Nuclear NME1 effector mediating MAPK activation unidentified
  13. 2012 High

    Defined a contact-dependent motility mechanism whereby NME1 enforces contact inhibition of locomotion by binding alpha-catenin/N-cadherin and inactivating Tiam1 to suppress Rac1; also linked NME1 to TGF-beta1/Snail-driven EMT.

    Evidence Reciprocal co-IPs, binding-mutant rescue, Rac1 activity and invasion assays; siRNA/shRNA rescue with EMT markers and Src/Snail involvement

    PMID:22718351 PMID:23137649

    Open questions at the time
    • How NME1 enzymatic activity drives Tiam1 inactivation unclear
    • EMT regulation lacks defined direct molecular target
  14. 2013 Medium

    Provided structural insight into both partner binding and redox regulation, mapping the h-Prune interaction interface and resolving a Cys4-Cys145 disulfide that dissociates the active hexamer into dimers.

    Evidence NMR of h-Prune C-terminus with competitive peptide inhibitor and in vivo neuroblastoma assays; X-ray crystallography, HDX, and tandem MS of oxidized NM23-H1

    PMID:23448979 PMID:23519676

    Open questions at the time
    • Quaternary-state dependence of each enzymatic activity not fully mapped
    • Whether disulfide formation occurs at physiological oxidant levels unaddressed
  15. 2017 Medium

    Connected NME1 to craniofacial development and defined its protein histidine kinase identity, showing IRF6 interaction (disrupted by CLP-associated R18Q with elevated Rac1/RhoA) and His118 autophosphorylation with substrate phosphorylation.

    Evidence Yeast two-hybrid, co-IP, palatal epithelial co-localization, Rho-GTPase and patient-variant assays; anti-pHis and anti-pH118 antibody immunoblotting in neuroblastoma cells/xenografts

    PMID:28767310 PMID:32392889

    Open questions at the time
    • pHis detection relies on antibody specificity without orthogonal validation
    • Physiological histidine-kinase substrates largely unidentified
  16. 2020 Medium

    Extended NME1 function to neuronal biology, identifying it as a necessary and sufficient mediator of GDF5-promoted neurite growth.

    Evidence Proteomics, in vivo GDF5 brain overexpression, siRNA, ectopic and exogenous NME1, neurite growth assays in SH-SY5Y and primary mDA neurons

    PMID:32853992

    Open questions at the time
    • Which enzymatic activity drives neurite growth unknown
    • Downstream effectors in neurons not defined
  17. 2023 Medium

    Identified upstream regulators of NME1 expression at the transcriptional (CTCF/EGR1) and post-transcriptional (NSUN6-mediated m5C) levels, explaining how aggressive tumors lose NME1.

    Evidence ChIP, promoter reporters and migration assays for CTCF/EGR1 (2021); m5C RIP, luciferase, and functional/xenograft assays for NSUN6 (2023)

    PMID:33436746 PMID:38029727

    Open questions at the time
    • Relative contribution of each regulatory layer in vivo unknown
    • Whether these regulators act coordinately is untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how NME1's distinct catalytic activities (NDPK, exonuclease, histidine kinase) are mechanistically integrated and selectively deployed to produce metastasis suppression, and what its in vivo histidine-kinase substrate repertoire is.
  • No unified model linking enzymatic activities to specific suppressor outputs
  • In vivo protein-histidine-kinase substrates uncharacterized
  • Quaternary-structure regulation of activity selection unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 3 GO:0016740 transferase activity 2 GO:0098772 molecular function regulator activity 2 GO:0140097 catalytic activity, acting on DNA 2 GO:0003677 DNA binding 1 GO:0016787 hydrolase activity 1 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 2 GO:0005815 microtubule organizing center 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-1643685 Disease 3 R-HSA-162582 Signal Transduction 2 R-HSA-1640170 Cell Cycle 2 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-8953897 Cellular responses to stimuli 2 R-HSA-73894 DNA Repair 1
Partners
CDC42CTNNA1IRF6PRUNESTRAPTIAM1TP53TXNRD1

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 NM23-H1 (nm23-H1) and NM23-H2 proteins both exhibit nucleoside diphosphate kinase (NDPK) enzymatic activity, catalyzing phosphotransfer from ATP to nucleoside diphosphates (e.g., GDP→GTP) via a phosphoenzyme intermediate; recombinant GST-fusion proteins expressed in E. coli formed [32P]-phosphoenzyme intermediates and converted GDP to GTP as shown by TLC. In vitro enzymatic assay with recombinant GST-fusion proteins; [γ-32P]ATP phosphoenzyme intermediate formation; TLC detection of GTP synthesis International journal of oncology High 21584562
2001 NM23-H1 binds to and cleaves the C-rich strand of the PDGF-A promoter nuclease-hypersensitive element (5'-SHS) at distinct 3'-sites relative to NM23-H2, and both proteins repress PDGF-A promoter-driven transcription in HepG2 cells, revealing a DNA-binding/cleavage-dependent transcriptional repression mechanism. Screening of HeLa cDNA expression library with PDGF-A silencer C-rich strand; recombinant protein DNA cleavage assays; transient transfection reporter assays in HepG2 cells The Journal of biological chemistry High 11694515
2004 NM23-H1 possesses intrinsic 3'-5' exonuclease activity that excises single nucleotides stepwise from DNA 3' termini in a Mg2+-dependent manner, preferring single-stranded substrates or mismatched 3' ends; Lys12 is critical for catalysis, as K12Q substitution greatly diminishes activity. In vitro exonuclease assay with recombinant wild-type and K12Q mutant NM23-H1; hydroxylapatite and gel filtration HPLC co-purification; inhibition by ATP and cordycepin incorporation The Journal of biological chemistry High 14960567
1999 Human PRUNE protein physically interacts with NM23-H1 (the human homolog of Drosophila awd), as demonstrated by yeast two-hybrid interaction-mating and in vitro co-immunoprecipitation; the NM23-H1 S120G gain-of-function mutant loses this interaction. PRUNE and NM23-H1 partially co-localize in the cytoplasm. Yeast two-hybrid interaction-mating; in vitro co-immunoprecipitation; confocal co-localization Oncogene Medium 10602478
2007 NM23-H1 suppresses tumor cell motility at least in part by transcriptionally down-regulating the lysophosphatidic acid receptor EDG2 (LPA1); mutants P96S and S120G fail to down-regulate EDG2 and fail to suppress motility; EDG2 overexpression in NM23-H1-expressing cells restores motility 60-fold. Expression microarray of MDA-MB-435 cells overexpressing wild-type vs. mutant NM23-H1; transfection/in vitro motility (Boyden chamber) assays; EDG2 siRNA knockdown Cancer research High 17671192 18089805
2007 NM23-H1 transcriptional down-regulation of EDG2/LPA1 is functionally critical for metastasis suppression in vivo: EDG2 co-expression with NM23-H1 restored cell lung retention 8–13-fold and restored pulmonary metastasis incidence from 51.9% to 90.4% in spontaneous metastasis assay. Human breast carcinoma cohort showed a statistically significant inverse correlation (r=−0.73) between NM23-H1 and EDG2 protein levels. Fluorescent cell tracking/ex vivo microscopy for lung retention; spontaneous metastasis xenograft assay; in vitro motility/invasion assays; human tumor cohort immunohistochemistry Cancer research High 18089805
2007 NM23-H1 and its binding partner STRAP directly bind to p53's central DNA-binding domain (residues 113–290) via NM23-H1 Cys145 and p53 Cys176; this complex potentiates p53-mediated transcription, apoptosis, and growth inhibition, and works by displacing Mdm2 from the p53–Mdm2 complex. Co-immunoprecipitation; domain-mapping with deletion/point mutants; luciferase reporter transcription assays; apoptosis and growth inhibition assays; siRNA knockdown of NM23-H1/STRAP The Journal of biological chemistry Medium 17916563
2011 The 3'-5' exonuclease activity of NM23-H1 is necessary for its metastasis suppressor function in vivo: exonuclease-deficient mutants E5A and K12Q failed to suppress spontaneous lung metastasis of 1205LU melanoma cells in mice, while retaining the ability to suppress motility/invasion in culture, indicating the exonuclease contributes specifically to in vivo metastasis suppression. Site-directed mutagenesis; in vitro exonuclease and NDPK assays; stable transfection of melanoma cell lines; spontaneous lung metastasis xenograft assay; in vitro Boyden chamber motility/invasion assays International journal of cancer High 20209495
2011 NM23-H1 promotes repair of UV-induced (6-4) photoproduct DNA damage; NM23-H1 deficiency compromised nucleotide excision repair kinetics; NM23-H1 rapidly translocated to sites of UV-induced DNA damage in the nucleus; its kinase activity was critical for rapid repair and 3'-5' exonuclease activity dominant in suppression of UV-induced mutagenesis. Nm23-M1/M2 hemizygous-null transgenic mice developed UV-induced melanoma. DNA repair kinetics assay (total polymerase-blocking lesions; (6-4) photoproduct NER); nuclear translocation imaging; transgenic knockout mouse UV-induced melanoma model Cancer research High 22080566
2010 NM23-H1 provides a local source of GTP for the GTPase dynamin during cytokinesis; loss of NM23-H1 in diploid cells causes cytokinetic furrow regression and cytokinesis failure generating tetraploid cells; dynamin loss phenocopies NM23-H1 loss; ectopic overexpression of dynamin complements NM23-H1 loss. RNAi knockdown; live-cell imaging of cytokinesis; ectopic dynamin overexpression rescue; flow cytometry for ploidy Proceedings of the National Academy of Sciences of the United States of America High 20713695
2009 NM23-H1 NDPK enzymatic activity is regulated by oxidative modification of Cys109: H2O2-induced oxidation (intra/inter-disulfide, glutathionylation, sulfonic acid) inhibits NDPK activity and metastasis suppressor activity; thioredoxin reductase 1 (TrxR1) interacts specifically with oxidized NM23-H1 and restores NDPK activity via the NADPH-TrxR1-thioredoxin shuttle. C109A mutant retains both activities under oxidative stress. UPLC-ESI-q-TOF tandem MS for oxidation-site identification; in vitro NDPK activity assay; co-immunoprecipitation of TrxR1; in vitro TrxR1 reduction assay; site-directed mutagenesis (C109A); metastasis suppressor activity assay PloS one High 19956735
2013 Oxidative conditions cause an intramolecular disulfide bond between Cys4 and Cys145 in NM23-H1, triggering a large conformational change that dissociates the functional hexamer into dimers; this structural change facilitates further oxidation of Cys109 to sulfonic acid. Crystal structure of oxidized NM23-H1 was determined. X-ray crystallography; hydrogen/deuterium-exchange experiments; nanoUPLC-ESI-q-TOF tandem MS peptide sequencing Acta crystallographica. Section D, Biological crystallography High 23519676
2001 NM23-H1 (rat homolog Nm23-R1/NDPKbeta) localizes to the centrosome in dividing and non-dividing cells, is catalytically active there, and co-immunoprecipitates with γ-tubulin, a core centrosomal protein essential for microtubule nucleation. Confocal laser scanning microscopy; biochemical centrosome purification; co-immunoprecipitation with γ-tubulin Experimental cell research Medium 11139339
2012 NM23-H1 is essential for contact inhibition of locomotion (CIL) by suppressing Rac1 through inactivation of Tiam1 at cell-cell contact sites; NM23-H1 translocates to contact sites via association with α-catenin and N-cadherin; ephrin-B1 disrupts CIL by inhibiting NM23-H1 association with Tiam1, activating Rac1. Spheroid confrontation invasion assay; siRNA knockdown; transfection of NM23-H1 binding mutants; co-immunoprecipitation of NM23-H1 with α-catenin, N-cadherin, and Tiam1; Rac1 activity assay Journal of cell science High 22718351
2010 NM23-H1 overexpression suppresses hepatocarcinoma cell adhesion and migration on fibronectin by impairing glycosylation of integrin β1, reducing mature β1 integrin on the cell surface (while mRNA levels are unchanged) and attenuating FAK phosphorylation. Stable transfection of NM23-H1; adhesion and wound-healing migration assays on fibronectin; flow cytometry for surface integrin; Western blot for mature vs. precursor integrin β1 isoforms; tunicamycin deglycosylation control Journal of experimental & clinical cancer research Medium 20618991
2012 NM23-H1 negatively regulates TGF-β1-induced epithelial-mesenchymal transition (EMT) in lung cancer cells; NM23-H1 knockdown enhanced TGF-β1-induced loss of E-cadherin and upregulation of β-catenin and fibronectin; this effect was Snail-dependent and involved Src kinase; ectopic re-expression of shRNA-resistant NM23-H1 reversed the knockdown phenotype. siRNA/shRNA knockdown; ectopic NM23-H1 re-expression rescue; Western blot for EMT markers; invasion/migration assays; Snail and Src kinase involvement assessed Experimental cell research Medium 23137649
2010 NM23-H1 forms a complex with transcription factor AP-1 and with p53 in B cells; NM23-H1 expression down-regulates cyclin D1 promoter activity in a dose-responsive manner, inducing cell cycle arrest and apoptosis (upregulating caspase 3/9, Bcl-x, p53; reducing cyclin D1). Microarray pathway analysis; real-time PCR validation; promoter-reporter (cyclin D1) assay; co-immunoprecipitation of NM23-H1 with AP-1 and p53; proliferation and apoptosis assays Cancer biology & therapy Medium 20448457
2009 NM23-H1 interacts with Cdc42 (endogenous proteins), as validated by reciprocal co-immunoprecipitation in K562 leukemia cells; NM23-H1 knockdown reduced Cdc42 protein expression and impaired megakaryocytic differentiation. Reciprocal co-immunoprecipitation; functional proteomics (2D-DIGE/MS); flow cytometry (CD41); ploidy analysis Life sciences Medium 19302816
2011 KSHV-encoded LANA promotes nuclear translocation of NM23-H1; nuclear NM23-H1 is required for Ras-BRaf-MAPK pathway activation and cell invasiveness induced by KSHV; cytoplasmic overexpression of NM23-H1 (via DNA demethylation agent) reduced KSHV-associated MAPK activation and invasiveness. Subcellular fractionation; confocal imaging; siRNA knockdown; ectopic LANA expression; MAPK pathway activation assays; invasion assays; pharmacologic DNA methylation inhibitor Journal of virology Medium 21270158
2013 NM23-H1/h-Prune complex formation identified by NMR spectroscopy of h-Prune C-terminal domain; a competitive permeable peptide (CPP) disrupting the Nm23-H1/h-Prune complex impaired cell motility, tumor growth, and metastasis formation in neuroblastoma models. NMR spectroscopy conformational analysis; competitive peptide inhibitor (CPP) design; cell motility assays; in vivo xenograft tumor growth and metastasis assay Scientific reports Medium 23448979
2017 NME1 (NM23-H1) physically interacts with IRF6 in the cytoplasm of palatal epithelial cells; this interaction is enhanced by phosphorylation of key serine residues in the IRF6 C-terminus. CLP-associated NME1 missense mutation R18Q disrupts IRF6 binding and leads to elevated Rac1 and RhoA activation. Yeast two-hybrid screen; co-immunoprecipitation; in vivo co-localization in primary palatal epithelial cells; Rac1/RhoA activation assays; patient variant functional testing Journal of dental research Medium 28767310
2017 NME1 (NM23-H1) and NME2 act as protein histidine kinases that phosphorylate histidine residues on themselves (via His118 phosphohistidine intermediate) and on substrate proteins; anti-pHis antibodies detected pH118-NME1/2 and multiple pHis-containing proteins in neuroblastoma cell lines and xenograft tumors. Anti-1- and 3-pHis monoclonal antibodies; anti-pH118 NME1/2 polyclonal antibodies; immunoblotting of neuroblastoma cell lines and xenograft tumor lysates International journal of molecular sciences Medium 32392889
2020 GDF5 neurotrophic factor increases NME1 expression in SH-SY5Y neuronal cells and in adult rat brain in vivo; NME1 expression is necessary and sufficient for GDF5-promoted neurite growth; exogenous NME1 protein treatment increased neurite growth in SH-SY5Y cells and in cultured midbrain dopaminergic neurons. Proteomics analysis; in vivo GDF5 overexpression in rat brain; siRNA knockdown; ectopic expression; quantitative neurite growth assays in SH-SY5Y and primary mDA neurons iScience Medium 32853992
2023 NSUN6 methyltransferase regulates NM23-H1 mRNA expression by depositing m5C modification on the 3'-UTR of NM23-H1 mRNA, stabilizing/promoting its expression; NSUN6 overexpression restricts lung cancer cell proliferation, migration, and EMT via elevated NM23-H1. m5C RIP (methylated RNA immunoprecipitation); dot blot; luciferase assay; qRT-PCR/Western blot; functional cell assays (CCK-8, wound-healing, transwell); in vivo xenograft Medical principles and practice Medium 38029727
2021 Transcription factors CTCF and EGR1 bind the proximal NM23-H1 promoter and induce NM23-H1 expression, thereby reducing MDA-MB-231 breast cancer cell migration; loss of CTCF and EGR1 in aggressive breast cancer cells correlates with reduced NM23-H1 levels. Promoter truncation/luciferase reporter analysis; ChIP (chromatin immunoprecipitation) of CTCF and EGR1 at NM23-H1 promoter; ectopic CTCF/EGR1 expression; wound-healing migration assay Scientific reports Medium 33436746
1997 NM23-H1 down-regulation by antisense oligonucleotides or stable antisense-transfection in MCF10A cells directly inhibits cell proliferation, demonstrating a role for NM23-H1 in cell cycle progression. Antisense oligonucleotide treatment; stable antisense transfection; cell proliferation assay; cell cycle synchronization and S-phase analysis International journal of cancer Medium 9335458

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1991 Identification of a second human nm23 gene, nm23-H2. Cancer research 412 1988104
2000 Nm23/nucleoside diphosphate kinase in human cancers. Journal of bioenergetics and biomembranes 189 11768314
1992 Proliferation-related expression of p19/nm23 nucleoside diphosphate kinase. The Journal of clinical investigation 157 1311721
1993 Reduced expression of nm23-H1, but not of nm23-H2, is concordant with the frequency of lymph-node metastasis of human breast cancer. International journal of cancer 149 8102131
2005 Medroxyprogesterone acetate elevation of Nm23-H1 metastasis suppressor expression in hormone receptor-negative breast cancer. Journal of the National Cancer Institute 102 15870434
2007 Nm23-H1 suppresses tumor cell motility by down-regulating the lysophosphatidic acid receptor EDG2. Cancer research 100 17671192
2001 NM23-H1 and NM23-H2 repress transcriptional activities of nuclease-hypersensitive elements in the platelet-derived growth factor-A promoter. The Journal of biological chemistry 99 11694515
1998 A new human nm23 homologue (nm23-H5) specifically expressed in testis germinal cells. FEBS letters 98 9742940
2003 Basic and translational advances in cancer metastasis: Nm23. Journal of bioenergetics and biomembranes 97 12848344
1993 Nm23 and breast cancer metastasis. Breast cancer research and treatment 91 8347849
1994 Expression of human nm23-H1 and nm23-H2 proteins in hepatocellular carcinoma. Cancer 86 8168032
2007 NM23-H1 tumor suppressor and its interacting partner STRAP activate p53 function. The Journal of biological chemistry 82 17916563
2004 The metastasis suppressor NM23-H1 possesses 3'-5' exonuclease activity. The Journal of biological chemistry 82 14960567
2007 Nm23-H1 suppresses metastasis by inhibiting expression of the lysophosphatidic acid receptor EDG2. Cancer research 74 18089805
2001 Expression of nm23-H1 in transitional cell carcinoma of the upper urinary tract. Oncology reports 73 11115597
1998 NM23-NDP kinase. The international journal of biochemistry & cell biology 73 9924799
1993 Expression of nm23/NDP kinase proteins on the cell surface. Oncogene 73 8386830
2008 Clinical-translational approaches to the Nm23-H1 metastasis suppressor. Clinical cancer research : an official journal of the American Association for Cancer Research 71 18698018
1995 NM23-H1 and NM23-H2 messenger RNA abundance in human hepatocellular carcinoma. Cancer research 69 7530600
1999 Evidence for interaction between human PRUNE and nm23-H1 NDPKinase. Oncogene 68 10602478
1993 Expression of nm23-H1 and nm23-H2 proteins in prostate carcinoma. Japanese journal of cancer research : Gann 67 7693635
2005 Lycopene inhibits cell migration and invasion and upregulates Nm23-H1 in a highly invasive hepatocarcinoma, SK-Hep-1 cells. The Journal of nutrition 63 16140886
2009 The NM23 family in development. Molecular and cellular biochemistry 60 19421718
2011 Metastasis suppressor function of NM23-H1 requires its 3'-5' exonuclease activity. International journal of cancer 58 20209495
2010 The Nm23-H1 metastasis suppressor as a translational target. European journal of cancer (Oxford, England : 1990) 53 20304626
1997 Down-regulation of the nm23.h1 gene inhibits cell proliferation. International journal of cancer 53 9335458
1998 Nm23 and tumour metastasis: basic and translational advances. Biochemical Society symposium 49 9513729
2011 Metastasis suppressor NM23-H1 promotes repair of UV-induced DNA damage and suppresses UV-induced melanomagenesis. Cancer research 47 22080566
2017 The actions of NME1/NDPK-A and NME2/NDPK-B as protein kinases. Laboratory investigation; a journal of technical methods and pathology 46 29200201
2011 Protein-protein interactions: a mechanism regulating the anti-metastatic properties of Nm23-H1. Naunyn-Schmiedeberg's archives of pharmacology 45 21713383
2006 Nm23-H1: a metastasis-associated gene. Taiwanese journal of obstetrics & gynecology 41 17197349
2020 NME/NM23/NDPK and Histidine Phosphorylation. International journal of molecular sciences 40 32823988
2009 Multiple functions of Nm23-H1 are regulated by oxido-reduction system. PloS one 40 19956735
2006 Potential roles of 3'-5' exonuclease activity of NM23-H1 in DNA repair and malignant progression. Journal of bioenergetics and biomembranes 40 17039395
2001 Identification of the tumor metastasis suppressor Nm23-H1/Nm23-R1 as a constituent of the centrosome. Experimental cell research 40 11139339
1997 Suppression of human melanoma metastasis following introduction of chromosome 6 is independent of NME1 (Nm23). Clinical & experimental metastasis 40 9174127
2021 CTCF and EGR1 suppress breast cancer cell migration through transcriptional control of Nm23-H1. Scientific reports 37 33436746
2004 Nucleoside diphosphate kinase A/nm23-H1 promotes metastasis of NB69-derived human neuroblastoma. Molecular cancer research : MCR 37 15280446
1995 Expression of nm23-H1 predicts lymph node involvement in colorectal carcinoma. Diseases of the colon and rectum 36 7774480
2004 nm23-H1 expression and loss of heterozygosity in colon adenocarcinoma. Journal of clinical pathology 35 15563674
2008 Nanoparticle delivery of anti-metastatic NM23-H1 gene improves chemotherapy in a mouse tumor model. Cancer gene therapy 34 19096443
1998 Inhibition of colonization and cell-matrix adhesion after nm23-H1 transfection of human prostate carcinoma cells. Cancer letters 34 10072163
2020 The Potential Functional Roles of NME1 Histidine Kinase Activity in Neuroblastoma Pathogenesis. International journal of molecular sciences 33 32392889
2020 miR-146a promoted breast cancer proliferation and invasion by regulating NM23-H1. Journal of biochemistry 32 31598678
2020 The Function of NM23-H1/NME1 and Its Homologs in Major Processes Linked to Metastasis. Pathology oncology research : POR 32 31993913
2007 Nm23-H1 homologs suppress tumor cell motility and anchorage independent growth. Clinical & experimental metastasis 32 18058029
1994 nm23-H1 expression and disease recurrence after surgical resection of small hepatocellular carcinoma. Gastroenterology 32 8039626
2013 Neuroblastoma tumorigenesis is regulated through the Nm23-H1/h-Prune C-terminal interaction. Scientific reports 31 23448979
2010 Nucleoside diphosphate kinase Nm23-H1 regulates chromosomal stability by activating the GTPase dynamin during cytokinesis. Proceedings of the National Academy of Sciences of the United States of America 31 20713695
1998 Expression of nm23-H1 gene and Sialyl Lewis X antigen in breast cancer. Oncology 31 9663428
2010 Nm23-H1 can induce cell cycle arrest and apoptosis in B cells. Cancer biology & therapy 30 20448457
2009 The Nm23-H1-h-Prune complex in cellular physiology: a 'tip of the iceberg' protein network perspective. Molecular and cellular biochemistry 29 19390954
2020 Nm23-H1 inhibits lung cancer bone-specific metastasis by upregulating miR-660-5p targeted SMARCA5. Thoracic cancer 28 32022430
2006 H-prune-nm23-H1 protein complex and correlation to pathways in cancer metastasis. Journal of bioenergetics and biomembranes 28 17103319
2004 Clinical significance of intracytoplasmic nm23-H1 expression in diffuse large B-cell lymphoma. Clinical cancer research : an official journal of the American Association for Cancer Research 28 15073128
2001 Expression of p16, nm23-H1, E-cadherin, and CD44 gene products and their significance in nasopharyngeal carcinoma. The Laryngoscope 28 11568585
1994 Expression and mutational analysis of Nm23-H1 in liver metastases of colorectal cancer. British journal of cancer 28 7981087
2023 NSUN6 Regulates NM23-H1 Expression in an m5C Manner to Affect Epithelial-Mesenchymal Transition in Lung Cancer. Medical principles and practice : international journal of the Kuwait University, Health Science Centre 26 38029727
2009 Double knockout Nme1/Nme2 mouse model suggests a critical role for NDP kinases in erythroid development. Molecular and cellular biochemistry 26 19381783
1995 Increased expression of the NME1 gene is associated with metastasis in epithelial ovarian cancer. International journal of cancer 26 7622307
2013 Structure of Nm23-H1 under oxidative conditions. Acta crystallographica. Section D, Biological crystallography 25 23519676
2012 nm23-H1 is a negative regulator of TGF-β1-dependent induction of epithelial-mesenchymal transition. Experimental cell research 25 23137649
2011 Regulation of Nm23-H1 and cell invasiveness by Kaposi's sarcoma-associated herpesvirus. Journal of virology 25 21270158
2005 Expression of the nm23 homologues nm23-H4, nm23-H6, and nm23-H7 in human gastric and colon cancer. The Journal of pathology 25 15726650
2005 Clinical significance of serum NM23-H1 protein in neuroblastoma. Cancer science 25 16232196
2017 NDPKA is not just a metastasis suppressor - be aware of its metastasis-promoting role in neuroblastoma. Laboratory investigation; a journal of technical methods and pathology 24 28991262
2012 Nm23-H1 regulates contact inhibition of locomotion, which is affected by ephrin-B1. Journal of cell science 24 22718351
2011 Correlation of NM23-H1 cytoplasmic expression with metastatic stage in human prostate cancer tissue. Naunyn-Schmiedeberg's archives of pharmacology 24 21553004
2014 NDK-1, the homolog of NM23-H1/H2 regulates cell migration and apoptotic engulfment in C. elegans. PloS one 23 24658123
2009 Nm23-M5 mediates round and elongated spermatid survival by regulating GPX-5 levels. FEBS letters 23 19303412
2008 Downregulated NM23-H1 expression is associated with intracranial invasion of nasopharyngeal carcinoma. British journal of cancer 23 18219290
2006 Read-through transcript from NM23-H1 into the neighboring NM23-H2 gene encodes a novel protein, NM23-LV. Genomics 23 16442775
2023 The ASH1L-AS1-ASH1L axis controls NME1-mediated activation of the RAS signaling in gastric cancer. Oncogene 22 37805663
2010 Nm23-H1 suppresses hepatocarcinoma cell adhesion and migration on fibronectin by modulating glycosylation of integrin beta1. Journal of experimental & clinical cancer research : CR 22 20618991
1996 Expression of NM23 in human melanoma progression and metastasis. British journal of cancer 22 8679442
1993 The human NME2 gene lies within 18kb of NME1 in chromosome 17. Genes, chromosomes & cancer 22 7685630
2017 Disrupted IRF6-NME1/2 Complexes as a Cause of Cleft Lip/Palate. Journal of dental research 21 28767310
2009 Nm23-H1 regulates the proliferation and differentiation of the human chronic myeloid leukemia K562 cell line: a functional proteomics study. Life sciences 21 19302816
2006 Nm23/NDP kinases in hepatocellular carcinoma. Journal of bioenergetics and biomembranes 21 16944304
2005 Expression and significance of heparanase and nm23-H1 in hepatocellular carcinoma. World journal of gastroenterology 21 15761980
2014 The metastasis suppressor Nm23 as a modulator of Ras/ERK signaling. Journal of molecular signaling 20 24829611
2011 Functional modulation of the metastatic suppressor Nm23-H1 by oncogenic viruses. FEBS letters 20 21846466
1992 Human nm23-h1-protein and h2-protein have similar nucleoside diphosphate kinase-activities. International journal of oncology 20 21584562
2009 Regulators affecting the metastasis suppressor activity of Nm23-H1. Molecular and cellular biochemistry 19 19377884
2006 Expression of Nm23 in gliomas and its effect on migration and invasion in vitro. Anticancer research 19 16475705
1999 The association between nm23-H1 expression and survival in patients with esophageal squamous cell carcinoma. Cancer letters 19 10378785
2021 Activation of Nm23-H1 to suppress breast cancer metastasis via redox regulation. Experimental & molecular medicine 18 33753879
2009 Clinical significance of altered nm23-H1, EGFR, RB and p53 expression in bilharzial bladder cancer. BMC cancer 18 19171060
1996 Increased levels of nm23 H1/nucleoside diphosphate kinase A mRNA associated with adenocarcinoma of the prostate. World journal of urology 17 8738406
2015 Transcriptional factor FOXO3 negatively regulates the expression of nm23-H1 in non-small cell lung cancer. Thoracic cancer 16 26816534
2011 Melanoma-associated genes, MXI1, FN1, and NME1, are hypoxia responsive in murine and human melanoma cells. Melanoma research 16 21912348
2008 A clinicopathological study of nm23-H1 expression in classical Hodgkin's lymphoma. Annals of oncology : official journal of the European Society for Medical Oncology 16 18647967
2020 miR-141-3p promotes proliferation and metastasis of nasopharyngeal carcinoma by targeting NME1. Advances in medical sciences 15 32299022
2017 RGS19 upregulates Nm23-H1/2 metastasis suppressors by transcriptional activation via the cAMP/PKA/CREB pathway. Oncotarget 15 29050254
1999 Organization and expression of mouse nm23-M1 gene. Comparison with nm23-M2 expression. Gene 15 10452942
1998 Nm23-H1 expression in intrahepatic or extrahepatic metastases of hepatocellular carcinoma. Liver 15 9831363
1998 The p53 and nm23-H1 genes are not deleted in oral benign epithelial lesions. Anticancer research 15 9858935
2020 STRAP and NME1 Mediate the Neurite Growth-Promoting Effects of the Neurotrophic Factor GDF5. iScience 14 32853992
2008 Changes of histology and expression of MMP-2 and nm23-H1 in primary and metastatic gastric cancer. World journal of gastroenterology 14 18330957
1998 Relationship between expression of CD44v6 and nm23-H1 and tumor invasion and metastasis in hepatocellular carcinoma. World journal of gastroenterology 14 11819333

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