Affinage

MYC

Myc proto-oncogene protein · UniProt P01106

Round 2 corrected
Length
454 aa
Mass
50.6 kDa
Annotated
2026-04-29
130 papers in source corpus 46 papers cited in narrative 47 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MYC encodes a nuclear bHLH-Zip transcription factor that heterodimerizes with Max to bind E-box sequences (CACGTG) and functions as a master regulator of cell proliferation, apoptosis, metabolism, and immune evasion (PMID:2006410, PMID:1587829). Rather than activating a discrete set of target genes, c-Myc amplifies the existing transcriptional program of active genes by promoting RNA Pol II pause release, directly inducing cell-cycle drivers (CDK4, E2F1 via miR-17-92), metabolic reprogramming enzymes (glutaminase via miR-23a/b repression, PKM2 via hnRNP upregulation), and immune checkpoint ligands CD47 and PD-L1 (PMID:20434984, PMID:23021215, PMID:10688915, PMID:19219026, PMID:20010808, PMID:26966191). c-Myc protein stability is governed by an integrated phospho-degron switch—GSK3-mediated Thr58 phosphorylation targets c-Myc to SCF(FBXW7)- and CRY2/FBXL3-dependent ubiquitination and degradation, while Ser62 phosphorylation by ERK/Pim kinases stabilizes the protein, with opposing PP2A holoenzymes (B56α dephosphorylating pS62 to destabilize; B55α/Eya3 dephosphorylating pT58 to stabilize) and multiple deubiquitinases (USP28, USP37, USP43) and SENP1-mediated deSUMOylation providing additional layers of control (PMID:15150404, PMID:27840026, PMID:24927563, PMID:29535359, PMID:25284584, PMID:38218970, PMID:30305424). Beyond transcription, c-Myc directly participates in DNA replication initiation by interacting with pre-replicative complex components, and its deregulation causes replication stress, reactive oxygen species, and genomic instability that are counteracted by p53-dependent apoptosis (PMID:17597761, PMID:12049739, PMID:1555236, PMID:8091232).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 1990 High

    Establishing that c-Myc negatively autoregulates its own promoter in a dose-dependent manner revealed an intrinsic feedback mechanism constraining its expression, setting the stage for understanding how deregulation (e.g., translocation) bypasses this control.

    Evidence Transfection of activated c-myc constructs into Rat-1 fibroblasts with run-on transcription measurements

    PMID:2182320

    Open questions at the time
    • trans-acting cofactors required for autorepression were not identified
    • mechanism of promoter sensing (cis elements) not defined
  2. 1991 High

    Identification of Max as the obligate heterodimerization partner for c-Myc DNA binding resolved how c-Myc, which binds DNA poorly alone, achieves sequence-specific E-box recognition, establishing the Myc-Max paradigm central to all subsequent target gene studies.

    Evidence cDNA expression library screen with bHLH-Zip bait; co-immunoprecipitation; EMSA with purified proteins

    PMID:1587829 PMID:2006410

    Open questions at the time
    • structural basis of heterodimerization not yet resolved
    • role of Max homodimers as antagonists not yet explored
  3. 1992 High

    Demonstrating that constitutive c-Myc expression induces apoptosis—using the same domains required for transformation—established the dual nature of c-Myc as both an oncogene and a pro-apoptotic factor, resolving the paradox of why tumors must disable apoptosis for Myc-driven oncogenesis.

    Evidence Conditional c-Myc expression in Rat-1 fibroblasts with domain-deletion mutants and serum deprivation

    PMID:1555236

    Open questions at the time
    • downstream apoptotic effectors not identified at this stage
    • cell-type dependence of apoptotic threshold not established
  4. 1994 High

    Placing p53 as an epistatic mediator of c-Myc-induced apoptosis explained how p53 loss cooperates with Myc in tumorigenesis by disconnecting the apoptotic failsafe from proliferative signaling.

    Evidence Conditional MycER activation in wild-type vs. p53-null fibroblasts; p53 protein stabilization

    PMID:8091232

    Open questions at the time
    • mechanism by which c-Myc stabilizes p53 protein not defined
    • alternative p53-independent apoptotic pathways not excluded
  5. 1993 High

    Identification of ODC as a direct c-Myc transcriptional target through intronic E-boxes provided the first concrete downstream effector linking c-Myc to a specific biosynthetic pathway (polyamine synthesis).

    Evidence Promoter-reporter cotransfection with E-box mutagenesis and c-Myc domain deletions

    PMID:8356088

    Open questions at the time
    • physiological relevance of the HLH/Zip-independent transactivation not clarified
    • contribution of ODC to Myc-driven transformation not tested genetically
  6. 1998 High

    Discovery that c-MYC is a direct transcriptional target of the APC/β-catenin/Tcf-4 pathway connected Wnt signaling to proliferative gene expression and explained c-MYC overexpression in APC-mutant colorectal cancers.

    Evidence Reporter assays with Tcf-4 binding site mutants; APC/β-catenin gain- and loss-of-function in colorectal cancer cells

    PMID:9727977

    Open questions at the time
    • quantitative contribution of Wnt-driven MYC vs. other MYC-activating signals in vivo unknown
    • chromatin-level mechanism of Tcf-4 activation not addressed
  7. 2000 High

    Identifying CDK4 as a direct c-Myc target, with genetic rescue of c-Myc-deficient cell-cycle defects by ectopic CDK4, established a concrete mechanism for c-Myc-driven G1/S progression.

    Evidence SAGE; ChIP at CDK4 promoter; c-MYC-null RAT1 cells; CDK4 rescue

    PMID:10688915

    Open questions at the time
    • relative contribution of CDK4 vs. other Myc targets to proliferation not quantified
  8. 2001 High

    Multiple studies converged to define how upstream signals regulate c-myc transcription—C/EBPα represses it via E2F sites during myeloid differentiation, Smad3/E2F-4 mediate TGF-β repression by displacing p300, and Src-Vav2-Rac activates it downstream of PDGF—revealing c-myc as an integrating node for diverse signaling pathways.

    Evidence Promoter deletion/mutation analyses; Co-IP for p300 dissociation; dominant-negative signaling epistasis in multiple cell types

    PMID:11340171 PMID:11389443 PMID:11689553

    Open questions at the time
    • chromatin remodeling events at the c-myc promoter during signal integration not resolved
    • combinatorial regulation by simultaneous signals not tested
  9. 2001 High

    Demonstration that c-Myc represses the PDGFβR gene by binding NF-Y subunits (YB/YC) through Myc homology boxes—without displacing NF-Y from DNA—revealed an E-box-independent repression mechanism expanding c-Myc's regulatory repertoire.

    Evidence GST pulldown; cellular Co-IP; GAL4-NF-YC transactivation assay with CCAAT mutants

    PMID:11282029

    Open questions at the time
    • genome-wide extent of Myc-NF-Y repression not determined
    • structural basis of Myc-NF-Y interaction unknown
  10. 2002 High

    Showing that deregulated c-Myc induces reactive oxygen species and DNA damage prior to S-phase, rescuable by antioxidants, established a direct mechanistic link between c-Myc overexpression and genomic instability independent of replication.

    Evidence Conditional c-Myc activation; comet assay; ROS measurement; antioxidant rescue in human fibroblasts

    PMID:12049739

    Open questions at the time
    • source of ROS (mitochondrial vs. enzymatic) not identified
    • specific oxidized DNA lesions not characterized
  11. 2004 High

    Reconstitution of SCF(FBXW7)-mediated c-Myc ubiquitination dependent on GSK3-phosphorylated Thr58 defined the core phospho-degron controlling c-Myc turnover and explained why T58 is a lymphoma hotspot mutation.

    Evidence In vitro ubiquitination reconstitution with FBXW7; T58 phospho-mutant analysis; in vivo degradation assays

    PMID:15150404

    Open questions at the time
    • relative contribution of FBXW7 vs. other E3 ligases to steady-state Myc turnover not quantified
  12. 2005 High

    Discovery that c-Myc directly activates the miR-17-92 cluster, whose products repress E2F1 translation, uncovered a feedforward loop whereby c-Myc fine-tunes its own proliferative output through miRNA regulation.

    Evidence ChIP for c-Myc at miR-17-92 locus; miRNA overexpression/knockdown; E2F1 3'UTR reporters

    PMID:15944709

    Open questions at the time
    • individual contributions of the six cluster miRNAs not fully delineated
  13. 2007 High

    Three parallel advances redefined c-Myc's scope: (1) a direct, transcription-independent role in DNA replication initiation via pre-RC interaction, (2) a ribosomal protein L11 negative feedback loop competing with TRRAP, and (3) genome-wide miRNA repression as a mechanism of lymphomagenesis.

    Evidence Xenopus cell-free replication extracts (transcription-free); Co-IP with pre-RC components; L11-MBII binding and TRRAP competition by ChIP; genome-wide miRNA ChIP in lymphoma models

    PMID:17597761 PMID:17599065 PMID:18066065

    Open questions at the time
    • structural basis of Myc-pre-RC interaction unknown
    • whether L11 feedback operates at all Myc target promoters not tested
    • selectivity of Myc-mediated miRNA repression vs. activation not fully explained
  14. 2008 High

    Identification of Pim kinases as stabilizers of c-Myc—Pim-2 directly phosphorylating Ser329 and Pim-1 modulating the Thr58/Ser62 balance—added a cooperative oncogenic kinase axis to the phospho-degron switch.

    Evidence In vitro kinase assay; phospho-site mutants; transformation assays

    PMID:18438430

    Open questions at the time
    • in vivo Pim-Myc axis contribution vs. PI3K/ERK not dissected genetically
  15. 2009 High

    Multiple discoveries linked c-Myc to metabolic reprogramming and replication stress: miR-23a/b repression upregulated glutaminase for glutamine catabolism, WRN helicase was shown essential for resolving c-Myc-driven replication stress, and p53-induced miR-145 was identified as a post-transcriptional suppressor of c-Myc, closing a p53-Myc regulatory loop.

    Evidence ChIP at miR-23a/b promoters with metabolic flux assays; BrdU pulse-chase with WRN siRNA and DNA damage markers; miR-145 3'UTR reporters with p53 RE validation

    PMID:19202062 PMID:19219026 PMID:19554081

    Open questions at the time
    • relative importance of glutaminase vs. other metabolic targets in Myc-driven tumors not established
    • how WRN is specifically recruited to Myc-induced aberrant structures unknown
  16. 2010 High

    Genome-wide studies revealed that c-Myc acts primarily through Pol II pause release rather than recruitment, and at high levels amplifies the existing transcriptional program rather than activating novel targets—fundamentally reframing c-Myc as a universal transcriptional amplifier.

    Evidence ChIP-seq/GRO-seq for Pol II and c-Myc; RNA-seq comparing high vs. low Myc tumor cells

    PMID:20434984 PMID:23021215

    Open questions at the time
    • how pause-release mechanism relates to Myc-mediated repression not reconciled
    • whether amplifier model applies to all tissues and contexts untested
  17. 2010 High

    Identification of miR-9 as a direct MYC/MYCN target that represses E-cadherin to promote invasiveness and angiogenesis via β-catenin/VEGF signaling established a miRNA-mediated mechanism for Myc-driven metastasis.

    Evidence ChIP at mir-9-3; CDH1 3'UTR reporter; metastasis mouse model

    PMID:20173740

    Open questions at the time
    • contribution of miR-9 vs. other EMT-promoting Myc targets to metastasis not quantified
  18. 2014 High

    Multiple new layers of c-Myc regulation were defined: USP37 as a deubiquitinase stabilizing c-Myc, PP2A-B56α/SET/CIP2A axis controlling pS62 dephosphorylation, and SerRS competing with c-Myc at the VEGFA promoter while recruiting SIRT2 to erase Myc-driven histone acetylation.

    Evidence In vitro DUB assay with catalytic mutant; phospho-specific Western blots with PP2A inhibitor manipulation; in vitro promoter competition and ChIP with SIRT2 Co-IP

    PMID:24927563 PMID:24940000 PMID:25284584

    Open questions at the time
    • USP37 substrate specificity beyond Myc not determined
    • physiological contexts where SerRS-Myc competition is rate-limiting unknown
  19. 2016 High

    Discovery that CRY2 recruits T58-phosphorylated c-Myc to an FBXL3-containing E3 ligase provided a circadian dimension to Myc turnover, while ELL was identified as a novel E3 ligase with a catalytic cysteine (C595) for direct Myc ubiquitination.

    Evidence Co-IP with T58 phospho-mutant and CRY1/CRY2 knockout comparison; ELL C595A catalytic mutant ubiquitination assay; xenograft validation

    PMID:27009366 PMID:27840026

    Open questions at the time
    • circadian oscillation of Myc protein in normal tissues not directly measured
    • ELL's relative contribution to total Myc ubiquitination unclear
  20. 2016 High

    MYC was shown to directly activate transcription of immune checkpoint genes CD47 and PD-L1, with genetic rescue demonstrating these are necessary for tumor immune evasion—establishing MYC as a direct link between oncogene activation and immunosuppression.

    Evidence ChIP at Cd47/Pd-l1 promoters; conditional MYC inactivation in mouse tumors; enforced CD47/PD-L1 rescue

    PMID:26966191

    Open questions at the time
    • whether MYC-driven immune evasion operates in all tumor types not tested
    • mechanism of MYC-dependent regulation of other immune modulators not explored
  21. 2018 High

    Two studies dissected opposing phosphatase arms controlling Myc stability: PP2A-B55α/Eya3 dephosphorylates pT58 to stabilize Myc, while PP2A-B56α dephosphorylates pS62 to destabilize it; separately, SENP1 was shown to deSUMOylate c-Myc, reducing polyubiquitination and stabilizing the protein, revealing SUMO-ubiquitin crosstalk in Myc turnover.

    Evidence In vitro phosphatase assays with B-subunit specificity; SENP1 catalytic mutant (C603S); phospho-specific and ubiquitin/SUMO blots

    PMID:29535359 PMID:30305424

    Open questions at the time
    • spatial regulation of PP2A holoenzyme assembly on Myc not addressed
    • SUMO acceptor lysines on Myc not mapped
  22. 2024 High

    USP43 was identified as a deubiquitinase targeting specific lysines (K148 and K289) on c-Myc and competing with FBXW7 for binding, forming a positive feedback loop that drives glycolysis and metastasis in bladder cancer.

    Evidence siRNA DUB library screen; lysine-specific mutant deubiquitination assays; FBXW7 competition Co-IP; metabolic and metastasis assays

    PMID:38218970

    Open questions at the time
    • whether USP43-Myc axis is relevant beyond bladder cancer not tested
    • structural basis of FBXW7/USP43 competition unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Despite detailed mapping of individual regulatory inputs, a quantitative integrated model of how phosphorylation, ubiquitination, SUMOylation, and O-GlcNAcylation combinatorially determine c-Myc half-life in specific tissues remains unbuilt; the structural basis of c-Myc's intrinsically disordered transactivation domain interactions with diverse partners (TRRAP, L11, NF-Y, pre-RC) also awaits high-resolution characterization.
  • no integrated quantitative model of multi-PTM crosstalk on Myc stability
  • no high-resolution structure of full-length Myc-Max in complex with chromatin or coactivators
  • tissue-specific variation in Myc regulatory network topology not systematically mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 12 GO:0003677 DNA binding 6
Localization
GO:0005634 nucleus 6
Pathway
R-HSA-392499 Metabolism of proteins 6 R-HSA-1640170 Cell Cycle 5 R-HSA-162582 Signal Transduction 3 R-HSA-1430728 Metabolism 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-168256 Immune System 1 R-HSA-69306 DNA Replication 1 R-HSA-9909396 Circadian clock 1
Partners
FBXW7MAXRPL11RPS14SENP1TRRAPUSP37USP43
Complex memberships
Myc-Max heterodimer

Evidence

Reading pass · 47 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 Max is a bHLH-Zip protein that specifically associates with c-Myc, N-Myc, and L-Myc via their HLH-Zip domains, and the Myc-Max heterodimer binds DNA in a sequence-specific manner (core CACGTG) under conditions where neither protein alone exhibits appreciable binding; DNA binding requires both the dimerization domain and basic region of c-Myc. cDNA expression library screen with c-Myc bHLH-Zip domain as bait; co-immunoprecipitation; EMSA; domain mutagenesis Science High 2006410
1992 c-Myc protein is a nuclear phosphoprotein that binds DNA with a consensus sequence PuACCACGTGCTC; purified full-length c-Myc from eukaryotic cells (baculovirus and CHO) exists in two forms: c-Myc alone and a complex with a copurifying 26–29 kDa protein, the latter binding DNA with higher affinity. Protein purification to near homogeneity; SELEX (systematic evolution of ligands by exponential enrichment); EMSA The Journal of biological chemistry High 1587829
1992 Constitutive c-Myc expression in Rat-1 fibroblasts induces apoptosis; domains of c-Myc required for apoptosis induction overlap with those required for cotransformation, autoregulation, and inhibition of differentiation; higher c-Myc levels increase susceptibility to apoptosis upon serum deprivation, and deregulated c-Myc induces apoptosis at multiple cell cycle points. Conditional c-Myc expression in Rat-1 fibroblasts; cell death assays; domain-deletion mutant analysis Cell High 1555236
1990 c-Myc protein negatively autoregulates its own gene transcription at the level of transcriptional initiation; the extent of suppression is proportional to cellular c-Myc concentration; autoregulation requires c-Myc protein plus additional trans-acting factors. Transient transfection of activated c-myc/v-myc into Rat-1 fibroblasts; run-on transcription assays; dose-response analysis The EMBO journal High 2182320
1993 The ornithine decarboxylase (ODC) gene is a direct transcriptional target of c-Myc; c-Myc transactivates ODC through conserved CACGTG repeats in intron 1; transactivation requires neither the leucine zipper of c-Myc nor its HLH domain, suggesting Myc may interact with transcription factors other than Max for ODC regulation. Promoter-reporter cotransfection assays; deletion and point mutagenesis of c-myc; heterologous promoter constructs Proceedings of the National Academy of Sciences of the United States of America High 8356088
1993 Yin-yang 1 (YY1) binds two sites in the murine c-myc promoter (at −260 and −390 bp from P1) and strongly activates c-myc transcription from both major initiation sites; YY1 is identical to the previously described common factor 1 (CF1) as shown by biochemical, immunological, and recombinant protein analyses. Protein purification; immunological cross-reactivity; recombinant YY1 binding assays; cotransfection reporter assays; overexpression in MEL cells measuring endogenous c-myc mRNA Molecular and cellular biology High 8246966
1994 c-Myc-induced apoptosis in quiescent mouse fibroblasts is mediated by p53; activation of c-Myc stabilizes p53, and p53-null fibroblasts undergo cell cycle re-entry but not apoptosis upon c-Myc activation, establishing p53 as an epistatic mediator of c-Myc-induced apoptosis. Conditional c-Myc activation (MycER fusion) in wild-type vs. p53-null fibroblasts; p53 stabilization Western blot; apoptosis assays Science High 8091232
1995 c-Myc is O-GlcNAc glycosylated on serine/threonine residues within or near its N-terminal transcription activation/transformation domain; the modification was demonstrated by lectin binding, glycosidase/glycosyltransferase treatment, and direct sugar characterization on purified recombinant protein. Lectin affinity assay; glycosidase/glycosyltransferase treatment; purification from insect and CHO cells; deletion mutant analysis Proceedings of the National Academy of Sciences of the United States of America High 7753821
1998 c-MYC is a transcriptional target of the APC/beta-catenin/Tcf-4 signaling pathway; wild-type APC represses c-MYC expression, and beta-catenin activates it through Tcf-4 binding sites in the c-MYC promoter, explaining c-MYC overexpression in colorectal cancers with APC mutations. Reporter assays with Tcf-4 binding site mutants; APC and beta-catenin gain/loss-of-function; endogenous c-MYC mRNA measurement Science High 9727977
1999 c-Myc overexpression causes colcemid-treated cells to become polyploid by replicating DNA without chromosomal segregation (uncoupling DNA replication from mitosis), and induces CDK2 activity in a G1-like state; in primary fibroblasts with wild-type p53, this triggers massive apoptosis instead. c-Myc overexpression in human and rodent cell lines; colcemid spindle checkpoint assay; flow cytometry; CDK2 kinase assay; primary vs. immortalized fibroblast comparison Molecular and cellular biology High 10409725
2000 CDK4 is a direct transcriptional target of c-MYC; c-MYC induces CDK4 mRNA through four conserved c-MYC binding sites in the CDK4 promoter; c-MYC-deficient RAT1 cells show delayed cell-cycle progression and impaired CDK4 induction, which is partially rescued by ectopic CDK4 expression. SAGE; promoter analysis with ChIP; c-MYC-deficient cell lines; CDK4 rescue experiments Proceedings of the National Academy of Sciences of the United States of America High 10688915
2001 C/EBPalpha directly represses c-Myc transcription through an E2F binding site in the c-Myc promoter; this repression is required for granulocytic differentiation, as stable ectopic c-Myc expression (from a C/EBPalpha-unresponsive promoter) blocks myeloid differentiation. Representational difference analysis; oligonucleotide array; promoter deletion/mutation analysis; stable c-Myc overexpression in C/EBPalpha-inducible myeloid cells; differentiation assays Molecular and cellular biology High 11340171
2001 c-Myc represses the PDGF beta-receptor by binding NF-Y subunits YB and YC (but not YA) through its Myc homology boxes (not the bHLHZip domain), without displacing NF-Y from DNA; instead, Myc represses NF-YC transactivation activity. Co-immunoprecipitation from cotransfected COS-1 cells; GST pulldown with in vitro translated c-Myc; luciferase reporter with CCAAT mutants; GAL4-NF-YC transactivation assay Journal of cell science High 11282029
2001 PDGF-induced c-myc expression is Src-dependent and proceeds through Vav2 activation of a Rac-dependent pathway, independently of Ras and the MAP kinase pathway. Dominant-negative and constitutively active signaling constructs; Src inhibition; c-myc promoter-reporter assays; epistasis analysis in NIH3T3 cells Nature cell biology High 11389443
2001 c-myc is a downstream target of TGF-beta/Smad signaling; Smad3 and E2F-4 directly bind a composite TIE/E2F element in the c-myc promoter; TGF-beta signaling suppresses c-myc transcription by dissociating p300 from E2F-4 without competing for DNA binding. EMSA; co-immunoprecipitation; promoter mutation analysis; chromatin-level timing experiments; p300 co-IP The Journal of biological chemistry High 11689553
2002 c-Myc can induce DNA damage and reactive oxygen species (ROS) prior to S phase in normal human fibroblasts; deregulated c-Myc partially disables the p53-mediated DNA damage response; antioxidant treatment reduces ROS, DNA damage, and p53 activation, linking c-Myc to genomic instability via oxidative stress. Conditional c-Myc activation; comet assay; ROS measurement; gene expression arrays; antioxidant rescue; clonogenic survival Molecular cell High 12049739
2004 Fbw7, the substrate recognition subunit of the SCF(Fbw7) ubiquitin ligase, promotes proteasome-dependent c-Myc degradation in vivo and c-Myc ubiquitination in vitro; this interaction and degradation require GSK3-mediated phosphorylation of c-Myc on threonine-58 (T58); T58 is the most frequent site of c-myc mutation in lymphoma. In vivo degradation assay; in vitro ubiquitination reconstitution; T58 phospho-mutant analysis; tumor cell line comparison Proceedings of the National Academy of Sciences of the United States of America High 15150404
2005 c-Myc directly activates expression of the miR-17-92 cluster (six miRNAs on chromosome 13) by binding to the locus, as shown by chromatin immunoprecipitation; two members of the cluster, miR-17-5p and miR-20a, negatively regulate E2F1 translation, revealing a mechanism by which c-Myc simultaneously activates E2F1 transcription and limits its translation. Chromatin immunoprecipitation (ChIP); miRNA overexpression and knockdown; E2F1 protein/mRNA measurement; luciferase reporter assays Nature High 15944709
2004 AID (activation-induced cytidine deaminase), the enzyme that initiates immunoglobulin class switch recombination, is essential for c-myc/IgH chromosome translocations in IL6-transgenic mice, directly linking aberrant CSR to oncogenic chromosome translocations. AID-knockout mouse model crossed with IL6-transgenic mice; cytogenetic analysis of c-myc/IgH translocations Cell High 15315756
2007 c-Myc has a direct, non-transcriptional role in DNA replication initiation: it interacts with pre-replicative complex components, localizes to early DNA synthesis sites, and its depletion from mammalian cells and Xenopus cell-free extracts (devoid of RNA transcription) impairs DNA replication; c-Myc overexpression increases replication origin activity, causing DNA damage and checkpoint activation. Co-immunoprecipitation with pre-RC components; DNA fiber assay; Xenopus cell-free replication extracts (transcription-independent); c-Myc depletion (siRNA); origin firing analysis; DNA damage markers Nature High 17597761
2007 Ribosomal protein L11 (a c-Myc transcriptional target) forms a negative feedback loop by binding to Myc box II (MBII) of c-Myc, competing with the coactivator TRRAP, and reducing histone H4 acetylation at c-Myc target gene promoters; L11 overexpression inhibits c-Myc transcriptional activity and cell proliferation, while L11 knockdown increases both. Co-immunoprecipitation; ChIP; siRNA knockdown; overexpression; histone acetylation assays; cell proliferation assays The EMBO journal High 17599065
2008 Pim-1 and Pim-2 kinases stabilize c-Myc protein in vivo; Pim-2 directly phosphorylates c-Myc on Ser329 to stabilize it; Pim-1 preferentially mediates decreased Thr58 phosphorylation and increased Ser62 phosphorylation; both kinases enhance c-Myc transcriptional activity and transforming ability through c-Myc stabilization. In vivo co-expression stabilization assays; in vitro kinase assay; phospho-site mutant analysis; transcriptional reporter assays; transformation assays Oncogene High 18438430
2009 c-Myc transcriptionally represses miR-23a and miR-23b, resulting in elevated mitochondrial glutaminase expression, thereby upregulating glutamine catabolism in cancer cells; this establishes c-Myc as a regulator of glutamine metabolism through miRNA-mediated control. ChIP showing c-Myc binding to miR-23a/b promoters; miRNA overexpression/knockdown; glutaminase protein measurement; metabolic flux assays Nature High 19219026
2009 c-Myc upregulates hnRNP proteins (PTB/hnRNPI, hnRNPA1, hnRNPA2) at the transcriptional level, which then bind repressively to sequences flanking PKM exon 9 to promote PKM2 isoform splicing, thereby promoting aerobic glycolysis (Warburg effect) in cancer cells. c-Myc ChIP on hnRNP promoters; overexpression/knockdown of hnRNPs; RT-PCR for PKM splicing; RNA-protein binding assays; glioma tissue correlation Nature High 20010808
2010 c-Myc regulates RNA Pol II promoter-proximal pause release rather than Pol II recruitment at its target genes; c-Myc is a key regulator of transcriptional pause release in mammalian cells, and this mechanism explains amplification of gene expression by c-Myc. ChIP-seq for Pol II and c-Myc; GRO-seq (global run-on sequencing); comparison of Pol II occupancy at promoters vs. gene bodies Cell High 20434984
2010 MYC directly binds the promoters of CD47 and PD-L1 genes and activates their transcription; MYC inactivation reduces CD47 and PD-L1 mRNA and protein levels and enhances the antitumor immune response; enforced CD47 or PD-L1 expression rescues tumor growth after MYC inactivation. ChIP showing MYC binding to Cd47 and Pd-l1 promoters; conditional MYC inactivation in mouse tumors; rescue experiments with enforced CD47/PD-L1 expression; immune cell analysis Science High 26966191
2012 In tumor cells with elevated c-Myc, the transcription factor accumulates at promoters of already-active genes and causes transcriptional amplification—increasing transcript levels from the existing gene expression program rather than activating new target genes. ChIP-seq; RNA-seq; GRO-seq; comparison of high vs. low Myc-expressing tumor cells; genome-wide occupancy analysis Cell High 23021215
2013 Ribosomal protein S14 (RPS14) binds to the Myc homology box II (MBII) and C-terminal bHLH-LZ domains of c-Myc, inhibits c-Myc transcriptional activity by preventing recruitment of c-Myc and TRRAP to target promoters, and promotes c-Myc mRNA degradation through an Argonaute2/miRNA pathway. Co-immunoprecipitation; domain-mapping pulldown; ChIP; siRNA knockdown; RT-qPCR; Argonaute2 epistasis The Journal of biological chemistry High 23775087
2014 USP37 is a deubiquitinating enzyme that directly interacts with and deubiquitinates c-Myc in a DUB-activity-dependent manner, stabilizing c-Myc and enhancing cell proliferation and the Warburg effect; USP37 depletion promotes c-Myc proteasomal degradation. USP screening; co-immunoprecipitation; in vivo and in vitro deubiquitination assays; catalytic mutant (DUB-inactive) analysis; cell proliferation assays Oncogene High 25284584
2014 The lncRNA PCGEM1 physically interacts with c-Myc, promotes its chromatin recruitment, and enhances c-Myc transactivation activity; PCGEM1 regulates multiple metabolic pathways in prostate cancer cells predominantly through c-Myc coactivation. RNA immunoprecipitation; co-immunoprecipitation; ChIP; promoter-reporter assays; PCGEM1 domain mapping for c-Myc binding Proceedings of the National Academy of Sciences of the United States of America Medium 25512540
2014 SerRS (seryl-tRNA synthetase) antagonizes c-Myc at the VEGFA promoter by two mechanisms: (1) direct competition blocking c-Myc from binding the promoter, and (2) recruiting SIRT2 histone deacetylase to erase c-Myc-promoted histone acetylation; nuclear localization of SerRS (conferred by a vertebrate-specific domain) is required for this anti-angiogenic activity. In vitro competition assays; ChIP; SIRT2 co-immunoprecipitation; histone acetylation assays; nuclear localization mutants; zebrafish vascular phenotype rescue eLife High 24940000
2014 PP2A (protein phosphatase 2A) dephosphorylates c-MYC at Ser62, destabilizing it; PP2A inhibitors SET (I2PP2A) and CIP2A are overexpressed in breast cancer and stabilize c-MYC by preventing PP2A-mediated dephosphorylation of S62; antagonizing SET with OP449 reduces S62 phosphorylation and c-MYC activity. PP2A inhibitor knockdown; phospho-specific Western blot for pS62-c-MYC; in vitro and in vivo tumor models; OP449 treatment Proceedings of the National Academy of Sciences of the United States of America High 24927563
2015 HBXIP interacts directly with c-Myc through leucine zippers, recruits the lncRNA Hotair as a scaffold, and the Hotair-bound histone demethylase LSD1 mediates c-Myc-dependent transcriptional activation of target genes; silencing HBXIP, Hotair, or LSD1 blocks c-Myc-enhanced cancer cell growth. Co-immunoprecipitation; RNA immunoprecipitation; ChIP; siRNA knockdown; in vitro and xenograft tumor growth assays Cancer research Medium 26719542
2016 CRY2 functions as a component of an FBXL3-containing E3 ubiquitin ligase that recruits T58-phosphorylated c-MYC for ubiquitylation and degradation; CRY1 cannot substitute for CRY2 in this process; this mechanism provides circadian control of c-MYC protein turnover. Co-immunoprecipitation; in vivo ubiquitylation assay; T58 phospho-mutant analysis; CRY1/CRY2 knockout comparison; proteasome inhibitor experiments Molecular cell High 27840026
2016 ELL (eleven-nineteen lysine-rich leukaemia) functions as a direct E3 ubiquitin ligase for c-Myc, with UbcH8 as the conjugating enzyme; Cys595 of ELL is the catalytic active site; ELL-mediated c-Myc ubiquitination and degradation inhibits c-Myc transcriptional activity and suppresses tumor growth in xenograft models. In vivo ubiquitination assay; active-site mutagenesis (C595A); Co-immunoprecipitation; c-Myc reporter assays; xenograft tumor growth Nature communications High 27009366
2018 SENP1 is a c-Myc deSUMOylating enzyme: it interacts with c-Myc, deSUMOylates it in cells and in vitro, and stabilizes it; catalytically inactive SENP1(C603S) cannot stabilize c-Myc; SENP1-mediated deSUMOylation reduces c-Myc polyubiquitination (SUMOylation promotes degradation) while promoting monoubiquitination and pS62/pT58 phosphorylation. Co-immunoprecipitation; in vitro deSUMOylation assay; catalytic mutant (C603S); ubiquitination assay; phospho-specific Western blot; cell cycle analysis Proceedings of the National Academy of Sciences of the United States of America High 30305424
2018 Eya3 co-opts the PP2A-B55α holoenzyme (its Ser/Thr phosphatase activity is not intrinsic to Eya3 but arises from interaction with PP2A-B55α) to dephosphorylate pT58 on c-Myc, stabilizing c-Myc; this opposes the canonical PP2A-B56α-mediated dephosphorylation of pS62 that destabilizes c-Myc. Co-immunoprecipitation of PP2A-B55α with Eya3; phosphatase assay; phospho-specific Western blot (pT58 vs pS62); c-Myc stability assay; xenograft metastasis model Nature communications High 29535359
2009 c-Myc overexpression in primary human fibroblasts markedly accelerates S-phase; WRN (Werner helicase) is required to support c-Myc-driven S-phase, as WRN depletion in c-Myc-overexpressing cells increases DNA damage at replication sites and activates an ATR-CHK1-CHK2-p53 'replication stress' pathway, leading to rapid senescence; p53 depletion rescues senescence. BrdU pulse-chase S-phase kinetics; c-Myc overexpression; WRN siRNA; DNA damage markers (γH2AX); ATR/CHK1/CHK2/p53 pathway analysis; senescence assay PloS one High 19554081
2009 p53 represses c-Myc post-transcriptionally by transcriptionally inducing miR-145 (via a p53 response element in the miR-145 promoter); miR-145 directly targets c-Myc mRNA; blockade of miR-145 reverses p53-mediated c-Myc repression. Promoter-reporter assay with p53 RE; miR-145 overexpression/anti-miR; 3'UTR luciferase reporter for c-Myc targeting; in vitro and in vivo tumor growth assays Proceedings of the National Academy of Sciences of the United States of America High 19202062
2001 Deregulated c-Myc expression in keratinocytes (K14.MYC2 transgenic mice) reduces beta1 integrin expression and depletes epidermal stem cells by 75%, impairing wound healing and keratinocyte migration; beta1 integrin is essential for both keratinocyte migration and stem cell maintenance. K14.MYC2 transgenic mouse model; label-retaining cell analysis for stem cells; beta1 integrin immunostaining; wound healing assays Nature genetics High 11381265
2024 USP43 stabilizes c-Myc by deubiquitinating it specifically at K148 and K289 through its deubiquitinase activity; USP43 competes with FBXW7 for c-Myc binding; USP43/c-Myc form a positive feedback loop in bladder cancer promoting glycolysis and metastasis. siRNA DUB library screen; co-immunoprecipitation; in vivo deubiquitination assay with lysine-specific mutants; FBXW7 competition assay; metabolic assays Cell death & disease High 38218970
2007 Myc broadly represses miRNA expression by directly binding miRNA promoters (ChIP), providing a widespread reprogramming of the miRNA transcriptome that contributes to B-cell lymphomagenesis; enforced expression of Myc-repressed miRNAs diminishes tumorigenic potential of lymphoma cells. Genome-wide ChIP for Myc at miRNA loci; miRNA profiling in human and mouse B-cell lymphoma models; miRNA overexpression functional assays Nature genetics High 18066065
2010 MYC and MYCN directly bind the mir-9-3 locus and activate miR-9 expression; miR-9 targets CDH1 (E-cadherin) mRNA, promoting cell motility and invasiveness; miR-9-mediated E-cadherin loss activates beta-catenin signaling, increasing VEGF expression and angiogenesis. ChIP for MYC/MYCN at mir-9-3 locus; miR-9 overexpression; 3'UTR luciferase reporter for CDH1; metastasis mouse model; sponge inhibition Nature cell biology High 20173740
2006 Endogenous c-Myc and Max protein-protein interactions can be directly visualized and quantified at single-molecule resolution in individual cells using proximity ligation; IFN-gamma signaling and small-molecule inhibitors (10058-F4) specifically regulate these interactions in situ. Proximity ligation assay (PLA) with antibodies against endogenous Myc and Max; rolling-circle amplification for single-molecule detection; quantification in response to IFN-gamma and small molecule inhibitors Nature methods High 17072308
2008 The small molecule 10058-F4 binds disordered c-Myc monomers and disrupts c-Myc-Max heterodimerization; the inhibitory effect depends on the Max isoform: p22 Max (which homodimerizes well) competes with c-Myc-Max heterodimerization, lowering the effective inhibitor concentration needed compared to p21 Max. Biophysical binding assays; EMSA for DNA binding; thermodynamic analysis of heterodimerization vs. homodimerization Bioorganic & medicinal chemistry letters Medium 19114306
2009 The ASK1-JNK pathway promotes c-Myc protein stability through phosphorylation at Ser62 and Ser71, which is required for c-Myc-dependent apoptosis; ASK1 signaling attenuates degradation of already-ubiquitinated c-Myc without affecting the ubiquitination process itself. ASK1 overexpression; phospho-site mutant c-Myc constructs (Ser62, Ser71); ubiquitination assay; proteasome inhibitor analysis; apoptosis assays Biochemical and biophysical research communications Medium 11243879
2009 c-Myc overexpression accelerates S-phase, and c-Myc-deficient fibroblasts exhibit prolonged S-phase; WRN helicase depletion in c-Myc-overexpressing cells causes DNA damage at active replication forks and activates ATR-CHK1-CHK2-p53 senescence pathway, suggesting WRN repairs aberrant replication structures caused by c-Myc-driven accelerated replication. BrdU pulse-chase S-phase kinetics; c-Myc overexpression and knockout fibroblasts; WRN siRNA; DNA damage markers at replication sites; senescence assay; p53 knockdown rescue PloS one High 19554081

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Identification of c-MYC as a target of the APC pathway. Science (New York, N.Y.) 4046 9727977
1992 Induction of apoptosis in fibroblasts by c-myc protein. Cell 3030 1555236
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
2005 c-Myc-regulated microRNAs modulate E2F1 expression. Nature 2308 15944709
2007 Reprogramming of human somatic cells to pluripotency with defined factors. Nature 2190 18157115
2011 Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 2101 21833088
2006 Direct observation of individual endogenous protein complexes in situ by proximity ligation. Nature methods 2000 17072308
1991 Max: a helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with Myc. Science (New York, N.Y.) 1807 2006410
2009 c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism. Nature 1763 19219026
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2012 Transcriptional amplification in tumor cells with elevated c-Myc. Cell 1227 23021215
2009 A census of human transcription factors: function, expression and evolution. Nature reviews. Genetics 1191 19274049
2016 MYC regulates the antitumor immune response through CD47 and PD-L1. Science (New York, N.Y.) 1145 26966191
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2010 miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Nature cell biology 1112 20173740
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2007 Widespread microRNA repression by Myc contributes to tumorigenesis. Nature genetics 1081 18066065
2010 c-Myc regulates transcriptional pause release. Cell 1059 20434984
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2006 The c-Myc target gene network. Seminars in cancer biology 960 16904903
2009 HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer. Nature 948 20010808
2011 Targeting MYC dependence in cancer by inhibiting BET bromodomains. Proceedings of the National Academy of Sciences of the United States of America 945 21949397
2002 c-MYC: more than just a matter of life and death. Nature reviews. Cancer 934 12360279
2013 Large-scale genotyping identifies 41 new loci associated with breast cancer risk. Nature genetics 895 23535729
2007 Genome-wide association study of prostate cancer identifies a second risk locus at 8q24. Nature genetics 890 17401363
2001 Ubiquitination of a new form of alpha-synuclein by parkin from human brain: implications for Parkinson's disease. Science (New York, N.Y.) 862 11431533
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2004 Integration of Smad and forkhead pathways in the control of neuroepithelial and glioblastoma cell proliferation. Cell 837 15084259
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2003 Genomic targets of the human c-Myc protein. Genes & development 803 12695333
2004 The Fbw7 tumor suppressor regulates glycogen synthase kinase 3 phosphorylation-dependent c-Myc protein degradation. Proceedings of the National Academy of Sciences of the United States of America 801 15150404
2012 Concurrent expression of MYC and BCL2 in diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 787 22851565
1993 The ornithine decarboxylase gene is a transcriptional target of c-Myc. Proceedings of the National Academy of Sciences of the United States of America 760 8356088
2007 HIF-1 inhibits mitochondrial biogenesis and cellular respiration in VHL-deficient renal cell carcinoma by repression of C-MYC activity. Cancer cell 747 17482131
2002 c-Myc can induce DNA damage, increase reactive oxygen species, and mitigate p53 function: a mechanism for oncogene-induced genetic instability. Molecular cell 747 12049739
1983 The human c-myc oncogene: structural consequences of translocation into the IgH locus in Burkitt lymphoma. Cell 746 6414718
1994 Mediation of c-Myc-induced apoptosis by p53. Science (New York, N.Y.) 738 8091232
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2009 p53 represses c-Myc through induction of the tumor suppressor miR-145. Proceedings of the National Academy of Sciences of the United States of America 714 19202062
2007 Non-transcriptional control of DNA replication by c-Myc. Nature 538 17597761
1984 Expression of c-myc changes during differentiation of mouse erythroleukaemia cells. Nature 424 6462247
2000 Identification of CDK4 as a target of c-MYC. Proceedings of the National Academy of Sciences of the United States of America 408 10688915
2008 Apoptotic signaling by c-MYC. Oncogene 407 18955973
1999 Mechanisms of apoptosis by c-Myc. Oncogene 371 10378693
2004 AID is required for c-myc/IgH chromosome translocations in vivo. Cell 369 15315756
2004 The life cycle of C-myc: from synthesis to degradation. Cell cycle (Georgetown, Tex.) 308 15467447
2021 Taking the Myc out of cancer: toward therapeutic strategies to directly inhibit c-Myc. Molecular cancer 307 33397405
1999 The role of c-myc in cellular growth control. Oncogene 304 10378694
1993 The role of c-myc in cell growth. Current opinion in genetics & development 291 8453273
1998 The many roles of c-Myc in apoptosis. Annual review of physiology 283 9558477
2001 Deregulated expression of c-Myc depletes epidermal stem cells. Nature genetics 270 11381265
2014 A long noncoding RNA connects c-Myc to tumor metabolism. Proceedings of the National Academy of Sciences of the United States of America 263 25512540
1990 Negative autoregulation of c-myc transcription. The EMBO journal 253 2182320
2001 c-Myc is a critical target for c/EBPalpha in granulopoiesis. Molecular and cellular biology 221 11340171
2001 c-myc is a downstream target of the Smad pathway. The Journal of biological chemistry 206 11689553
2008 Pim kinase-dependent inhibition of c-Myc degradation. Oncogene 205 18438430
2003 The many faces of c-MYC. Archives of biochemistry and biophysics 196 12893289
2002 The proto-oncogene c-myc in hematopoietic development and leukemogenesis. Oncogene 191 12032779
1995 Glycosylation of the c-Myc transactivation domain. Proceedings of the National Academy of Sciences of the United States of America 184 7753821
1991 c-myc inhibition of MyoD and myogenin-initiated myogenic differentiation. Molecular and cellular biology 179 1850105
1993 Yin-yang 1 activates the c-myc promoter. Molecular and cellular biology 172 8246966
2016 CRY2 and FBXL3 Cooperatively Degrade c-MYC. Molecular cell 168 27840026
2008 The c-myc promoter: still MysterY and challenge. Advances in cancer research 163 18037408
1992 Function of the c-Myc oncoprotein. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 163 1521738
2007 Inhibition of c-Myc activity by ribosomal protein L11. The EMBO journal 162 17599065
2014 Targeting c-MYC by antagonizing PP2A inhibitors in breast cancer. Proceedings of the National Academy of Sciences of the United States of America 158 24927563
1987 Regulatory elements that modulate expression of human c-myc. Genes & development 158 3428595
2012 Addiction to c-MYC in multiple myeloma. Blood 141 22806891
2020 CircECE1 activates energy metabolism in osteosarcoma by stabilizing c-Myc. Molecular cancer 137 33106166
1998 Regulation of c-myc expression by Ras/Raf signalling. Oncogene 134 9464539
2014 USP37 directly deubiquitinates and stabilizes c-Myc in lung cancer. Oncogene 133 25284584
1998 The proto-oncogene c-myc and apoptosis. Oncogene 131 9916997
2004 The role of c-myc in regulation of translation initiation. Oncogene 126 15094771
2010 Pim1 kinase synergizes with c-MYC to induce advanced prostate carcinoma. Oncogene 122 20140016
2001 Regulation of c-myc expression by PDGF through Rho GTPases. Nature cell biology 121 11389443
2008 Carrot and stick: HIF-alpha engages c-Myc in hypoxic adaptation. Cell death and differentiation 117 18188166
1999 c-Myc overexpression uncouples DNA replication from mitosis. Molecular and cellular biology 115 10409725
2015 HBXIP and LSD1 Scaffolded by lncRNA Hotair Mediate Transcriptional Activation by c-Myc. Cancer research 114 26719542
1993 The c-myc oncogene in tumor progression. Critical reviews in oncogenesis 108 8353142
2014 c-MYC-induced genomic instability. Cold Spring Harbor perspectives in medicine 104 24692190
1993 Electroporation enhances c-myc antisense oligodeoxynucleotide efficacy. Nucleic acids research 102 8346033
2022 Target c-Myc to treat pancreatic cancer. Cancer biology & therapy 101 34978469
1991 c-myc oncoprotein function. Biochimica et biophysica acta 99 1751543
2014 MicroRNAs as regulators and mediators of c-MYC function. Biochimica et biophysica acta 98 24727092
2001 Mechanism for the transcriptional repression by c-Myc on PDGF beta-receptor. Journal of cell science 97 11282029
1997 Defining a role for c-Myc in breast tumorigenesis. Breast cancer research and treatment 95 9164674
1987 Characterization of rat c-myc and adjacent regions. Nucleic acids research 94 3306601
2008 c-Myc: linking transformation and genomic instability. Current molecular medicine 88 18781952
2014 tRNA synthetase counteracts c-Myc to develop functional vasculature. eLife 84 24940000
2009 The c-MYC-AP4-p21 cascade. Cell cycle (Georgetown, Tex.) 81 19270520
2018 SUMO protease SENP1 deSUMOylates and stabilizes c-Myc. Proceedings of the National Academy of Sciences of the United States of America 77 30305424
2006 Aberrant stabilization of c-Myc protein in some lymphoblastic leukemias. Leukemia 76 16855632
2013 A c-Myc-MicroRNA functional feedback loop affects hepatocarcinogenesis. Hepatology (Baltimore, Md.) 75 23389829
2018 Eya3 partners with PP2A to induce c-Myc stabilization and tumor progression. Nature communications 73 29535359
2002 TIP49, but not TRRAP, modulates c-Myc and E2F1 dependent apoptosis. Oncogene 72 12185582
2013 Ribosomal protein S14 negatively regulates c-Myc activity. The Journal of biological chemistry 71 23775087
2009 c-Myc accelerates S-phase and requires WRN to avoid replication stress. PloS one 70 19554081
2020 FBXL6 governs c-MYC to promote hepatocellular carcinoma through ubiquitination and stabilization of HSP90AA1. Cell communication and signaling : CCS 69 32576198
2006 c-Myc overexpression and endocrine resistance in breast cancer. The Journal of steroid biochemistry and molecular biology 68 17052904
2016 Therapeutic aspects of c-MYC signaling in inflammatory and cancerous colonic diseases. World journal of gastroenterology 67 27672289
2014 Attacking c-Myc: targeted and combined therapies for cancer. Current pharmaceutical design 65 25341931
2006 c-Myc, genome instability, and tumorigenesis: the devil is in the details. Current topics in microbiology and immunology 62 16620029
2007 Feedback regulation of c-Myc by ribosomal protein L11. Cell cycle (Georgetown, Tex.) 58 18032916
2000 Frequent c-myc and Int-2 overrepresentations in nasopharyngeal carcinoma. Human pathology 58 10685630
2024 USP43 stabilizes c-Myc to promote glycolysis and metastasis in bladder cancer. Cell death & disease 57 38218970
2007 The ever expanding role for c-Myc in promoting genomic instability. Cell cycle (Georgetown, Tex.) 55 17426456
2008 Small-molecule perturbation of competing interactions between c-Myc and Max. Bioorganic & medicinal chemistry letters 53 19114306
2015 Integrin α1β1 expression is controlled by c-MYC in colorectal cancer cells. Oncogene 50 26096932
2021 TAZ is indispensable for c-MYC-induced hepatocarcinogenesis. Journal of hepatology 49 34464659
1992 Antisense c-myc oligodeoxyribonucleotide cellular uptake. Pharmaceutical research 49 1384028
1992 DNA binding activities of c-Myc purified from eukaryotic cells. The Journal of biological chemistry 49 1587829
2009 Mechanisms of c-myc degradation by nickel compounds and hypoxia. PloS one 48 20046830
1987 Effect of 4-hydroxynonenal on c-myc expression. Toxicologic pathology 45 3475758
2008 How the c-myc promoter works and why it sometimes does not. Journal of the National Cancer Institute. Monographs 44 18648001
2003 c-Myc-induced genomic instability. Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer 44 14529093
2014 Aurora kinase A mediates c-Myc's oncogenic effects in hepatocellular carcinoma. Molecular carcinogenesis 43 25284017
2007 Degrasyn activates proteasomal-dependent degradation of c-Myc. Cancer research 43 17440106
2015 SIRT1 Limits Adipocyte Hyperplasia through c-Myc Inhibition. The Journal of biological chemistry 42 26655722
2013 Sp1 and c-Myc regulate transcription of BMI1 in nasopharyngeal carcinoma. The FEBS journal 42 23601184
2020 Circadian regulation of c-MYC in mice. Proceedings of the National Academy of Sciences of the United States of America 40 32817420
2016 ELL targets c-Myc for proteasomal degradation and suppresses tumour growth. Nature communications 37 27009366
2015 Deubiquitinating c-Myc: USP36 steps up in the nucleolus. Cell cycle (Georgetown, Tex.) 35 26697836
1991 c-myc protooncogene polypeptide expression in endometriosis. American journal of obstetrics and gynecology 35 1707594
2014 Repression of PLA2R1 by c-MYC and HIF-2alpha promotes cancer growth. Oncotarget 34 24657971
2006 Glioma: what is the role of c-Myc, hsp90 and telomerase? Molecular and cellular biochemistry 33 16444580
2023 The DUBA-SLC7A11-c-Myc axis is critical for stemness and ferroptosis. Oncogene 32 37537342
2022 SLCO4A1-AS1 promotes colorectal tumourigenesis by regulating Cdk2/c-Myc signalling. Journal of biomedical science 32 35039060
2010 Critical role of Shp2 in tumor growth involving regulation of c-Myc. Genes & cancer 30 21442024
2001 ASK1-signaling promotes c-Myc protein stability during apoptosis. Biochemical and biophysical research communications 30 11243879
1997 c-myc in bladder cancer. Clinical findings and analysis of mechanism. Urological research 30 9079756