Affinage

MYCN

N-myc proto-oncogene protein · UniProt P04198

Length
464 aa
Mass
49.6 kDa
Annotated
2026-06-10
100 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MYCN encodes N-Myc, a Myc-family transcription factor that drives proliferation and oncogenic transformation across neural progenitors and multiple cancer lineages (PMID:3860871, PMID:10837031). N-Myc shares its three-exon gene architecture, long 5'UTR, and protein-family features with c-Myc, and can functionally replace c-Myc at the endogenous locus to support murine development, establishing that the two share core transcriptional and proliferative programs (PMID:10837031, PMID:3510398). Mechanistically, N-Myc is recruited to target promoters in living cells where it competes with other Max partners for E-box occupancy (PMID:11074604), and it both activates targets (FAK; the TRAIL receptor DR5 and Bid; the ASCT2/SLC1A5 glutamine transporter in cooperation with ATF4) and represses targets (parkin; LIF, the latter through an N-terminal domain independent of Myc/Max), coupling its transcriptional output to adhesion, apoptotic sensitization, glutaminolysis, and pluripotency-gene control (PMID:17327229, PMID:15632181, PMID:25142020, PMID:12153570, PMID:15078880, PMID:19495417). In neural development N-Myc acts downstream of Sonic hedgehog and Wnt/β-catenin signaling to drive progenitor proliferation, doing so in part by suppressing the CDK inhibitors p18Ink4c and p27Kip1 whose genetic loss rescues proliferation in N-Myc-null cerebella (PMID:16322694, PMID:20215343, PMID:16864777); it can also force postmitotic neurons into S-phase re-entry through an Rb-dependent pathway separable from its pro-survival activity (PMID:11826111). N-Myc protein stability is the dominant control point: sequential cyclin B/Cdk1 and GSK-3β phosphorylation primes SCF(Fbxw7)-mediated polyubiquitination and degradation, which is opposed by Aurora A kinase, which binds the Myc Box I-flanking region (resolved by crystallography) at a site overlapping the Fbxw7 docking site, and by the deubiquitinase HAUSP/USP7 (PMID:19111882, PMID:27837025, PMID:27618649, PMID:16322694). N-Myc cooperates with chromatin cofactors GCN5/KAT2A and HDAC5 to maintain its transcriptional and self-stabilizing programs (PMID:22745758, PMID:23812427), and beyond neuroblastoma it drives neuroendocrine prostate cancer in cooperation with AKT1, ALK, and Wnt/β-catenin signaling (PMID:27728805, PMID:27050099, PMID:33637566).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1986 Medium

    Establishing that N-myc is a c-myc-related gene with a defined protein product framed it as a Myc-family transcription factor rather than an isolated amplicon.

    Evidence Genomic sequencing of human N-myc and immunoprecipitation of the 62-64 kDa protein from neuroblastoma cells

    PMID:3008339 PMID:3510398

    Open questions at the time
    • Sequence kinship did not establish DNA-binding specificity or partner requirements
    • No functional transcriptional assay in these studies
  2. 1987 High

    Demonstrating that N-Myc transforms fibroblasts alone or with Ha-ras assigned it bona fide oncogenic activity equivalent to c-Myc.

    Evidence Co-transfection transformation and soft-agar/tumorigenicity assays in rat fibroblasts

    PMID:3299052 PMID:3860871

    Open questions at the time
    • Transformation readout did not define the transcriptional targets responsible
    • Fibroblast context differs from the neural lineage where N-Myc normally acts
  3. 1992 Medium

    Showing IL-7-driven N-myc induction occurs via release of a transcriptional attenuation block clarified how its expression is gated in a developmental-stage-specific manner.

    Evidence Nuclear run-on transcription assays in normal pre-B cells

    PMID:1730410

    Open questions at the time
    • Attenuation mechanism characterized in B-lineage, not neural cells
    • Did not identify the trans-acting factors controlling attenuation
  4. 2000 High

    Knock-in complementation and ChIP recruitment together showed N-Myc shares c-Myc's core function and physically engages target promoters through Max-competitive binding.

    Evidence c-myc/N-myc coding-sequence knock-in mice and formaldehyde-crosslinking ChIP at telomerase/prothymosin promoters

    PMID:10837031 PMID:11074604

    Open questions at the time
    • ChIP limited to two target genes
    • Did not establish genome-wide occupancy or repression mechanisms
  5. 2007 Medium

    Mapping direct activating and repressing targets defined how N-Myc converts promoter binding into specific phenotypes spanning adhesion, apoptosis sensitization, metabolism, and pluripotency.

    Evidence EMSA/ChIP/reporter and promoter-mutagenesis studies on FAK, DR5/Bid, parkin, LIF, ASCT2, and pluripotency genes

    PMID:12153570 PMID:15078880 PMID:15632181 PMID:17327229 PMID:19495417 PMID:25142020

    Open questions at the time
    • Most targets validated in single labs on individual promoters
    • LIF repression via a Max-independent N-terminal domain was not structurally resolved
    • Relative contribution of each target to tumor phenotype unquantified
  6. 2010 High

    Genetic epistasis placed N-Myc as the proliferative effector downstream of Shh and Wnt/β-catenin that drives neural progenitor expansion by suppressing CDK inhibitors.

    Evidence Conditional N-myc knockouts, β-catenin gain-of-function, p18/p27 double-mutant rescue, and Rb-dependent S-phase re-entry assays

    PMID:11826111 PMID:16322694 PMID:16864777 PMID:20215343

    Open questions at the time
    • Whether CDK-inhibitor suppression is direct transcriptional repression not fully resolved
    • Survival pathway separable from cell-cycle re-entry remains molecularly undefined
  7. 2016 High

    Identifying the Cdk1/GSK3-Fbxw7 degradation axis and its antagonists Aurora A and USP7 established N-Myc protein abundance as a druggable control point.

    Evidence Co-IP, ubiquitination/phospho-mutagenesis assays, a 1.72 Å Aurora A–N-Myc crystal structure, and in vivo USP7 ablation/inhibitor studies

    PMID:19111882 PMID:27618649 PMID:27837025

    Open questions at the time
    • Whether Aurora A's stabilizing function is fully kinase-independent versus structural is incompletely separated
    • NEDD4 and other ligases noted but not mechanistically dissected
  8. 2013 Medium

    Linking N-Myc to chromatin cofactors GCN5 and HDAC5 connected its transcriptional output to histone acetylation and a feed-forward loop reinforcing its own stability.

    Evidence Co-IP, conditional GCN5 knockout phenocopy, histone-acetylation ChIP, and HDAC5 knockdown differentiation assays

    PMID:22745758 PMID:23812427

    Open questions at the time
    • Only a subset of N-Myc target genes shown to be cofactor-dependent
    • Direct versus indirect effects of HDAC5 on Aurora A/NEDD4 not resolved
  9. 2021 Medium

    Extending N-Myc oncogenesis to neuroendocrine prostate cancer showed it cooperates with AKT1, ALK, and Wnt/β-catenin and remains required for tumor maintenance and Aurora A-targetable.

    Evidence Genetically engineered and tissue-recombination mouse models, human prostate epithelial transformation, and Aurora A/ALK/Wnt pharmacologic inhibition

    PMID:27050099 PMID:27728805 PMID:30657058 PMID:33637566

    Open questions at the time
    • Cell-context-dependent miR-421/ATM regulation not mechanistically unified
    • Single-lab models for each cooperating oncogene

Open questions

Synthesis pass · forward-looking unresolved questions
  • How N-Myc's genome-wide target selection, repressive (Max-independent) activities, and cofactor switching are integrated to specify distinct lineage outcomes remains unresolved.
  • No unified structural model of N-Myc/Max/cofactor complexes on chromatin
  • Determinants of activation versus repression at individual promoters undefined
  • Role of the intron-1 antisense RNA duplex in regulating N-myc expression uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 2
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-1643685 Disease 4 R-HSA-1266738 Developmental Biology 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-1640170 Cell Cycle 2
Partners
ATF4AURKAFBXW7GCN5HDAC5MAXUSP7

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 Aurora A (AURKA) physically interacts with N-Myc and stabilizes it by counteracting SCF(Fbxw7)-mediated ubiquitination. Degradation of N-Myc requires sequential phosphorylation by cyclin B/Cdk1 and GSK3; Aurora A uncouples N-Myc stability from PI3-kinase/growth factor signals by binding both N-Myc and the SCF(Fbxw7) ubiquitin ligase. shRNA screen, co-immunoprecipitation, protein stability assays, phosphorylation site mutagenesis, ubiquitination assays Cancer Cell High 19111882
2016 Crystal structure (1.72 Å) of Aurora A catalytic domain in complex with a region of N-Myc flanking Myc Box I reveals direct binding; this Aurora-A-binding site also overlaps with the SCF(Fbxw7) docking site, suggesting that Aurora A stabilizes N-Myc by competing with SCF(Fbxw7) and disfavoring Lys48-linked polyubiquitin chain formation. Inhibitors such as alisertib and CD532 induce an Aurora A conformation incompatible with N-Myc binding. X-ray crystallography, in vitro binding assays, cell-based N-Myc stability assays PNAS High 27837025
2016 HAUSP/USP7 deubiquitinase physically interacts with N-Myc, deubiquitinates it, and thereby stabilizes N-Myc protein. RNAi-mediated knockdown of USP7 or genetic ablation of Usp7 destabilizes N-Myc and inhibits N-Myc function in neuroblastoma. Co-immunoprecipitation, RNAi knockdown, in vivo Usp7 genetic ablation, ubiquitination assay, xenograft mouse model with USP7 inhibitors Nature Medicine High 27618649
1985 N-Myc can cooperate with activated Ha-ras to transform normal primary rat embryo fibroblasts, demonstrating oncogenic/transforming activity comparable to c-Myc. Gene co-transfection transformation assay, soft-agar colony formation, syngeneic rat tumorigenicity assay PNAS High 3860871
1987 N-Myc can act alone (without ras) to elicit neoplastic transformation of Rat-1 fibroblasts, causing morphological transformation, anchorage-independent growth, and tumorigenicity; both N-myc and c-myc produce similar phenotypes from the same vectors. Gene transfection, soft-agar colony formation, tumorigenicity assay in vivo Molecular and Cellular Biology Medium 3299052
1986 Overexpression of N-myc in rat neuroblastoma cells via gene transfer causes down-modulation of MHC class I histocompatibility antigen expression in a cell-type-specific manner, and increases in vivo growth rate and metastatic ability; interferon treatment reverses MHC class I down-modulation without affecting N-myc mRNA. Gene transfer, FACS for MHC class I, in vivo metastasis assay, interferon treatment Cell Medium 3096575
1991 N-myc transfection in neuroblastoma cells suppresses PKC-delta isoform expression and induces PKC-zeta, blocking phorbol ester-mediated activation of c-fos mRNA and NF-κB; reintroduction of a PKC expression vector restores this inducibility, placing N-myc upstream of PKC-mediated signal transduction. Gene transfection, Northern blotting, reporter assay for NF-κB and c-fos, PKC rescue experiment The EMBO Journal Medium 1902412
2000 N-Myc is directly recruited to the promoters of telomerase and prothymosin target genes in living neuroblastoma cells and competes with other Max partners for binding, as demonstrated by chromatin immunoprecipitation showing that Max occupancy is high before and after N-Myc induction but N-Myc occupancy increases dramatically with overexpression. Formaldehyde cross-linking chromatin immunoprecipitation (ChIP), differential expression screens, neuroblastoma cell culture Molecular Carcinogenesis Medium 11074604
2007 N-MYC directly binds to the FAK promoter and transcriptionally activates FAK expression in neuroblastoma; two N-MYC binding sites in the FAK promoter were identified, and loss of FAK in N-MYC-expressing cells decreases viability and increases apoptosis. Electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation (ChIP), dual-luciferase reporter assay, siRNA knockdown, dominant-negative FAK Journal of Biological Chemistry Medium 17327229
2005 N-Myc sensitizes neuroblastoma cells to TRAIL-induced apoptosis by transcriptionally up-regulating TRAIL receptor-2 (DR5) and Bid via two non-canonical E-boxes in the DR5 promoter; N-Myc-induced apoptosis requires Smac/DIABLO but not cytochrome c-mediated caspase-9 activation. N-Myc overexpression, TRAIL apoptosis assay, DR5 promoter reporter with E-box mutagenesis, Western blotting for apoptotic intermediates Journal of Biological Chemistry Medium 15632181
2000 N-Myc can functionally replace c-Myc in murine development: mice in which N-myc coding sequences replace endogenous c-myc survive to adulthood and reproduce, demonstrating that N-Myc and c-Myc share core transcriptional and proliferative functions when expressed from the same locus. Knock-in mouse genetics (homologous recombination replacing c-myc with N-myc coding sequences), developmental and cellular phenotype analysis Genes & Development High 10837031
2006 N-Myc acts downstream of Sonic hedgehog (Shh) signaling in cerebellar granule neuron progenitors; degradation of N-Myc triggered by GSK-3β-mediated phosphorylation (primed by Cdk1) is required for progenitor cell-cycle exit. IGF signaling keeps GSK-3β in check to maintain N-Myc levels. Conditional N-myc knockout in cerebellum, phosphorylation assays, cell-cycle exit analysis Cell Cycle Medium 16322694
2006 Genetic disruption of cyclin-dependent kinase inhibitors p18Ink4c and p27Kip1 in N-Myc-null cerebella partially rescues granule neuron progenitor proliferation and cerebellar foliation, establishing that N-Myc promotes proliferation by suppressing these CDK inhibitors. Compound conditional knockout genetics, cell proliferation assays, cerebellar morphology analysis PNAS High 16864777
2010 Wnt/β-catenin signaling promotes basal progenitor production in the developing neocortex via N-myc; expression of stabilized β-catenin or N-myc increases basal progenitor numbers, while conditional deletion of N-myc reduces basal progenitors and cortical neuron number, placing N-myc downstream of Wnt signaling. In utero electroporation, conditional N-myc knockout, β-catenin gain-of-function mouse, BrdU labeling, neural progenitor quantification Development High 20215343
2002 In postmitotic sympathetic neurons, N-myc expression at neuroblastoma-like levels induces S-phase re-entry (measured by BrdU incorporation and cell cycle protein expression) while protecting neurons from apoptosis caused by NGF withdrawal; cell cycle re-entry but not survival is blocked by constitutively hypophosphorylated Rb, indicating that N-myc uses separate pathways for cell cycle and survival. Adenoviral gene delivery to postmitotic neurons, BrdU incorporation, Rb dominant-negative epistasis, apoptosis assay Journal of Neuroscience Medium 11826111
2013 HDAC5 and N-Myc form a protein complex that co-represses a subset of genes in neuroblastoma; N-Myc upregulates HDAC5 expression, and HDAC5 in turn increases Aurora A expression and decreases NEDD4 ligase expression, thereby further stabilizing N-Myc protein. HDAC5 knockdown reduces proliferation and promotes differentiation. Co-immunoprecipitation, genome-wide gene expression analysis, siRNA knockdown, neuroblastoma differentiation assay Oncogene Medium 23812427
2009 N-Myc directly binds the LIF promoter and represses LIF transcription in a manner independent of Myc/Max interaction, requiring instead a contiguous N-terminal N-Myc domain, as shown by promoter reporter assays using N-Myc deletion mutants. Promoter-reporter assay with N-Myc deletion mutants, Northern blotting, adenoviral STAT3 phosphorylation-deficient mutant rescue European Journal of Biochemistry Medium 12153570
2004 N-myc binds a conserved site in the parkin promoter and represses parkin transcription, as shown by ChIP and promoter-reporter assays; parkin expression is inversely correlated with N-myc levels in developing brain, neuroblastoma cell lines, and an inducible N-myc cell line. ChIP, promoter-reporter assay, inducible N-myc cell line, expression correlation in brain development and neuroblastoma Journal of Biological Chemistry Medium 15078880
2009 N-Myc directly binds the LIF promoter (ChIP assay) and regulates expression of pluripotency genes (lif, klf2, klf4, lin28b) in neuroblastoma and neural stem cells; N-Myc also regulates histone H3 lysine 4 trimethylation at the lif promoter, linking N-Myc transcriptional activity to active chromatin marks. ChIP-chip, direct ChIP, microarray expression profiling, Tet-regulatable N-myc system, nestin-cre N-myc knockout neural stem cells PLoS ONE Medium 19495417
2016 N-Myc overexpression drives neuroendocrine prostate cancer (NEPC) in a genetically engineered mouse model and induces Polycomb Repressive Complex 2 (EZH2) signaling with abrogation of androgen receptor signaling. Genetically engineered mouse model (MYCN overexpression), transcriptome analysis, integration with human NEPC data Cancer Cell Medium 27728805
2016 N-Myc and activated AKT1 together are sufficient to transform human prostate epithelial cells into prostate adenocarcinoma and NEPC; N-Myc is required for tumor maintenance, and Aurora A kinase inhibition destabilizes N-Myc and reduces tumor burden. Lentiviral transduction of human prostate epithelial cells, xenograft mouse model, Aurora A inhibitor treatment Cancer Cell Medium 27050099
2014 ATF4 cooperates with N-Myc to directly activate ASCT2 (SLC1A5) glutamine transporter expression in MYCN-amplified neuroblastoma cells; ASCT2 depletion inhibits glutaminolysis and reduces cell proliferation and tumourigenesis. Glutamine influx analysis, siRNA knockdown, luciferase reporter assay showing ATF4/N-Myc co-activation of ASCT2 promoter, xenograft assay Journal of Pathology Medium 25142020
1992 IL-7 induces rapid N-myc and c-myc expression in normal pre-B cells at the transcriptional level; for N-myc, induction is largely mediated by release of a transcriptional attenuation block between exons 1 and 2. More mature B-lineage cells respond to mitogens with c-myc but not N-myc induction, indicating developmental stage-specificity. Nuclear run-on transcription assay, Northern blotting, IL-7 stimulation of pre-B cells Genes & Development Medium 1730410
1990 N-myc mRNA forms an RNA-RNA duplex in vivo with endogenous antisense transcripts originating from intron 1; most cytoplasmic nonpolyadenylated antisense RNA exists as a duplex with ~5% of sense N-myc mRNA, and duplex formation involves a subset of N-myc mRNA species retaining intron 1, suggesting a role in modulating RNA processing. Nuclear run-off transcription, RNase protection assay for in vivo duplexes, cDNA cloning of both strands Molecular and Cellular Biology Medium 1695323
2019 N-Myc differentially regulates the miR-421/ATM pathway in a cell-context-dependent manner: in LNCaP cells, N-Myc overexpression upregulates miR-421 to suppress ATM, relieving ADT-induced senescence; in C4-2 cells, N-Myc upregulates ATM, promoting migration and Enzalutamide resistance. ATM knockout or inhibition re-sensitizes N-Myc-overexpressing cells to Enzalutamide. Stable N-Myc overexpression cell lines, CRISPR-Cas9 ATM knockout, SA-β-gal senescence assay, MTS viability assay, xenograft model Molecular Cancer Medium 30657058
2012 GCN5/KAT2A histone acetyltransferase functions as an N-Myc transcriptional cofactor in neural stem cells; approximately one-sixth of genes regulated by N-Myc loss are co-regulated by GCN5 loss, and GCN5 is required for maintenance of histone acetylation at N-Myc target gene promoters. Conditional knockout of GCN5 in NSC phenocopies N-Myc loss (microcephaly, reduced proliferation). Conditional knockout (nestin-cre), gene expression profiling, histone acetylation ChIP, phenotypic analysis PLoS ONE Medium 22745758
1986 Human N-myc and c-myc share a similar three-exon intron/exon structure with coding sequences in exons 2 and 3, long 5' untranslated regions, and significant protein sequence homology, indicating structural and functional kinship. Nucleotide sequencing, exon-intron structure analysis, protein sequence deduction Nature Medium 3510398
1986 The N-myc protein is 62-64 kDa as identified by immunoprecipitation from neuroblastoma cells using antisera raised against bacterially expressed N-myc fragments; it shares biochemical features with the c-myc protein family. Bacterial expression of N-myc antigen fragments, immunization, immunoprecipitation from neuroblastoma cell lysates Science Medium 3008339
2021 Coactivation of ALK (F1174C-activating mutation) and N-Myc is sufficient to transform mouse prostate basal stem cells into aggressive NEPC via Wnt/β-catenin pathway activation; ALK inhibition suppresses Wnt/β-catenin signaling and cooperates with Wnt inhibition to suppress tumor growth and metastasis. Tissue recombination mouse model, genetic coactivation, pharmacologic ALK/Wnt inhibition in vitro and in vivo Cancer Research Medium 33637566

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1985 Decreased expression of N-myc precedes retinoic acid-induced morphological differentiation of human neuroblastoma. Nature 634 3855502
1984 Expression and amplification of the N-myc gene in primary retinoblastoma. Nature 483 6728001
2009 Stabilization of N-Myc is a critical function of Aurora A in human neuroblastoma. Cancer cell 477 19111882
2016 N-Myc Induces an EZH2-Mediated Transcriptional Program Driving Neuroendocrine Prostate Cancer. Cancer cell 474 27728805
2016 N-Myc Drives Neuroendocrine Prostate Cancer Initiated from Human Prostate Epithelial Cells. Cancer cell 338 27050099
1986 N-myc amplification causes down-modulation of MHC class I antigen expression in neuroblastoma. Cell 329 3096575
1985 Human N-myc gene contributes to neoplastic transformation of mammalian cells in culture. Nature 295 4040214
1986 Gene amplification of c-myc and N-myc in small cell carcinoma of the lung. Science (New York, N.Y.) 281 3014659
1984 Activated expression of the N-myc gene in human neuroblastomas and related tumors. Science (New York, N.Y.) 265 6505694
1986 Human N-myc is closely related in organization and nucleotide sequence to c-myc. Nature 256 3510398
2000 N-myc can functionally replace c-myc in murine development, cellular growth, and differentiation. Genes & development 254 10837031
2010 The N-myc downstream regulated gene (NDRG) family: diverse functions, multiple applications. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 244 20667976
2008 Hematopoietic stem cell function and survival depend on c-Myc and N-Myc activity. Cell stem cell 239 19041778
1986 Nucleotide sequence of the human N-myc gene. Proceedings of the National Academy of Sciences of the United States of America 216 2869488
1985 N-myc can cooperate with ras to transform normal cells in culture. Proceedings of the National Academy of Sciences of the United States of America 214 3860871
2004 Oncogenic cooperation between H-Twist and N-Myc overrides failsafe programs in cancer cells. Cancer cell 209 15607966
2003 N-Myc downstream-regulated gene 2 (NDRG2) inhibits glioblastoma cell proliferation. International journal of cancer 193 12845671
1986 Enhanced expression of the N-myc gene in Wilms' tumors. Cancer research 181 2430692
1990 N-myc mRNA forms an RNA-RNA duplex with endogenous antisense transcripts. Molecular and cellular biology 174 1695323
2016 HAUSP deubiquitinates and stabilizes N-Myc in neuroblastoma. Nature medicine 172 27618649
1985 Expression of N-myc in teratocarcinoma stem cells and mouse embryos. Nature 165 3840574
1986 Structure and expression of the murine N-myc gene. Proceedings of the National Academy of Sciences of the United States of America 161 3513190
2016 Structural basis of N-Myc binding by Aurora-A and its destabilization by kinase inhibitors. Proceedings of the National Academy of Sciences of the United States of America 145 27837025
2014 ATF4 and N-Myc coordinate glutamine metabolism in MYCN-amplified neuroblastoma cells through ASCT2 activation. The Journal of pathology 137 25142020
1986 Identification and characterization of the protein encoded by the human N-myc oncogene. Science (New York, N.Y.) 132 3008339
1987 Neoplastic transformation by the human gene N-myc. Molecular and cellular biology 127 3299052
2005 N-myc down-regulated gene 1 modulates the response of term human trophoblasts to hypoxic injury. The Journal of biological chemistry 117 16314423
1991 Combined analysis of DNA ploidy index and N-myc genomic content in neuroblastoma. Cancer research 111 1988094
1988 N-myc oncogene RNA expression in neuroblastoma. Journal of the National Cancer Institute 101 2461451
1993 Mutation of the p53 gene in neuroblastoma and its relationship with N-myc amplification. Cancer research 98 8358734
2009 N-myc downstream regulated gene 1 (NDRG1) is fused to ERG in prostate cancer. Neoplasia (New York, N.Y.) 97 19649210
2019 N-Myc promotes therapeutic resistance development of neuroendocrine prostate cancer by differentially regulating miR-421/ATM pathway. Molecular cancer 96 30657058
1986 Amplification units containing human N-myc and c-myc genes. Proceedings of the National Academy of Sciences of the United States of America 88 3006024
1992 Interleukin-7 induces N-myc and c-myc expression in normal precursor B lymphocytes. Genes & development 85 1730410
2010 Extracellular matrix rigidity modulates neuroblastoma cell differentiation and N-myc expression. Molecular cancer 83 20144241
2006 Neural precursor cycling at sonic speed: N-Myc pedals, GSK-3 brakes. Cell cycle (Georgetown, Tex.) 80 16322694
1987 Expression of N-myc and c-src during the development of fetal human brain. Cancer research 80 3552210
2010 Wnt signaling and its downstream target N-myc regulate basal progenitors in the developing neocortex. Development (Cambridge, England) 78 20215343
2009 N-Myc regulates expression of pluripotency genes in neuroblastoma including lif, klf2, klf4, and lin28b. PloS one 78 19495417
2008 N-myc is a novel regulator of PI3K-mediated VEGF expression in neuroblastoma. Oncogene 78 18278068
2008 N-Myc downstream-regulated gene 2 is involved in p53-mediated apoptosis. Nucleic acids research 78 18689861
2011 Antitumor activity of sustained N-myc reduction in rhabdomyosarcomas and transcriptional block by antigene therapy. Clinical cancer research : an official journal of the American Association for Cancer Research 76 22065083
2007 N-MYC regulates focal adhesion kinase expression in human neuroblastoma. The Journal of biological chemistry 72 17327229
2009 Nmi (N-Myc interactor) inhibits Wnt/beta-catenin signaling and retards tumor growth. International journal of cancer 64 19358268
2002 N-myc promotes survival and induces S-phase entry of postmitotic sympathetic neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 64 11826111
2011 Conditional deletion of N-Myc disrupts neurosensory and non-sensory development of the ear. Developmental dynamics : an official publication of the American Association of Anatomists 63 21448975
1991 N-myc disrupts protein kinase C-mediated signal transduction in neuroblastoma. The EMBO journal 63 1902412
2016 Emerging role of N-myc downstream-regulated gene 2 (NDRG2) in cancer. Oncotarget 62 26506239
2006 N-Myc and the cyclin-dependent kinase inhibitors p18Ink4c and p27Kip1 coordinately regulate cerebellar development. Proceedings of the National Academy of Sciences of the United States of America 61 16864777
1999 Co-amplification of a novel gene, NAG, with the N-myc gene in neuroblastoma. Oncogene 61 9926938
2001 Inhibition of N-myc expression and induction of apoptosis by iron chelation in human neuroblastoma cells. Cancer research 59 11221835
2012 N-myc and noncoding RNAs in neuroblastoma. Molecular cancer research : MCR 57 22936790
2000 N-myc and c-myc expression in Alzheimer disease, Huntington disease and Parkinson disease. Brain research. Molecular brain research 57 10837922
2021 Activated ALK Cooperates with N-Myc via Wnt/β-Catenin Signaling to Induce Neuroendocrine Prostate Cancer. Cancer research 54 33637566
2000 Direct recruitment of N-myc to target gene promoters. Molecular carcinogenesis 52 11074604
2012 N-Myc and GCN5 regulate significantly overlapping transcriptional programs in neural stem cells. PloS one 51 22745758
2008 N-Myc down-regulated gene 1 mediates proliferation, invasion, and apoptosis of hepatocellular carcinoma cells. Cancer letters 50 18207320
1991 Episome-generated N-myc antisense RNA restricts the differentiation potential of primitive neuroectodermal cell lines. Molecular and cellular biology 50 1996098
1990 Differential regulation of the N-myc gene in transfected cells and transgenic mice. Molecular and cellular biology 50 2183019
2008 Reduced expression of N-Myc downstream-regulated gene 2 in human thyroid cancer. BMC cancer 48 18940011
2011 N-myc controls proliferation, morphogenesis, and patterning of the inner ear. The Journal of neuroscience : the official journal of the Society for Neuroscience 47 21562282
2004 N-myc regulates parkin expression. The Journal of biological chemistry 47 15078880
2010 c-myc and N-myc promote active stem cell metabolism and cycling as architects of the developing brain. Oncotarget 43 20651942
1991 N-myc genomic content and DNA ploidy in stage IVS neuroblastoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 43 2072140
2011 Didymin induces apoptosis by inhibiting N-Myc and upregulating RKIP in neuroblastoma. Cancer prevention research (Philadelphia, Pa.) 42 22174364
2004 Integration of woodchuck hepatitis and N-myc rearrangement determine size and histologic grade of hepatic tumors. Hepatology (Baltimore, Md.) 42 15057905
1997 Modulation of N-myc expression alters the invasiveness of neuroblastoma. Clinical & experimental metastasis 42 9062389
2005 N-Myc functions in transcription and development. Birth defects research. Part C, Embryo today : reviews 41 16425253
2016 N-Myc overexpression increases cisplatin resistance in neuroblastoma via deregulation of mitochondrial dynamics. Cell death discovery 38 28028439
2020 Beyond the Warburg Effect: N-Myc Contributes to Metabolic Reprogramming in Cancer Cells. Frontiers in oncology 37 32547946
2003 N-Myc overexpression leads to decreased beta1 integrin expression and increased apoptosis in human neuroblastoma cells. Oncogene 37 12730680
2014 N-Myc interactor inhibits prototype foamy virus by sequestering viral Tas protein in the cytoplasm. Journal of virology 36 24719420
2013 Histone deacetylase 5 blocks neuroblastoma cell differentiation by interacting with N-Myc. Oncogene 36 23812427
2005 Linking of N-Myc to death receptor machinery in neuroblastoma cells. The Journal of biological chemistry 36 15632181
1992 The N-myc proto-oncogene: developmental expression and in vivo site-directed mutagenesis. Brain pathology (Zurich, Switzerland) 35 1341949
1991 Expression of L-myc and N-myc proto-oncogenes in human leukemias and leukemia cell lines. Blood 35 1954386
2017 N-myc regulates growth and fiber cell differentiation in lens development. Developmental biology 34 28716713
1992 Transcriptional down-regulation of N-myc expression during B-cell development. Molecular and cellular biology 34 1549113
2004 N-myc downregulated gene 1 is a phosphorylated protein in mast cells. Biological & pharmaceutical bulletin 33 15133234
1993 L-myc and N-myc in hematopoietic malignancies. Leukemia & lymphoma 32 8260894
2008 N-myc augments death and attenuates protective effects of Bcl-2 in trophically stressed neuroblastoma cells. Oncogene 31 18193081
2003 The N-myc paradox: N-myc overexpression in neuroblastomas is associated with sensitivity as well as resistance to apoptosis. Cancer letters 30 12880977
1988 Sequence of a germ-line N-myc gene and amplification as a mechanism of activation. Oncogene 30 2834684
2011 N-myc downstream-regulated gene 1 (NDRG1) a differentiation marker of human breast cancer. Pathology oncology research : POR 29 21221878
1990 Expression of the N-myc proto-oncogene during the early development of Xenopus laevis. Development (Cambridge, England) 29 2088727
2010 N-myc downstream regulated 1 gene and its place in the cellular machinery. Acta biochimica Polonica 27 20300662
2011 Sequential and coordinated actions of c-Myc and N-Myc control appendicular skeletal development. PloS one 26 21494559
1992 L-myc and N-myc influence lineage determination in the central nervous system. Neuron 26 1281420
2015 Burkitt lymphoma beyond MYC translocation: N-MYC and DNA methyltransferases dysregulation. BMC cancer 24 26453442
2013 The expression and localization of N-myc downstream-regulated gene 1 in human trophoblasts. PloS one 24 24066183
2002 N-myc oncogene overexpression down-regulates leukemia inhibitory factor in neuroblastoma. European journal of biochemistry 24 12153570
1993 The effect of N-myc amplification and expression on invasiveness of neuroblastoma cells. Journal of pediatric surgery 24 8331499
2016 NCYM is upregulated by lncUSMycN and modulates N-Myc expression. International journal of oncology 23 27748806
2015 Otx2 is a target of N-myc and acts as a suppressor of sensory development in the mammalian cochlea. Development (Cambridge, England) 23 26160903
2015 Nifurtimox reduces N-Myc expression and aerobic glycolysis in neuroblastoma. Cancer biology & therapy 23 26177922
1993 N-myc gene amplification/expression in localized stroma-rich neuroblastoma (ganglioneuroblastoma). Human pathology 23 8454274
2016 Roles of N-Myc and STAT interactor in cancer: From initiation to dissemination. International journal of cancer 22 26874464
2021 N-Myc promotes angiogenesis and therapeutic resistance of prostate cancer by TEM8. Medical oncology (Northwood, London, England) 20 34523032
1991 Transcription of N-myc and proliferation-related genes is linked in human neuroblastoma. Cancer letters 20 2004353
2004 N-myc downstream-regulated gene 1 expression in injured sciatic nerves. Glia 19 15293230

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