Affinage

MYC

Myc proto-oncogene protein · UniProt P01106

Length
454 aa
Mass
50.6 kDa
Annotated
2026-06-10
100 papers in source corpus 35 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

c-MYC is a sequence-specific transcription factor that, in complex with Max, binds E-box (CACGTG) elements located within open, pre-acetylated CpG-island promoters and further enhances local histone acetylation, coordinating cell proliferation, ribosome biogenesis, DNA replication, and apoptosis (PMID:12695333, PMID:15723053). Rather than recruiting RNA Pol II de novo, c-Myc principally stimulates release of promoter-proximally paused Pol II, and when overexpressed in tumor cells it accumulates at already-active promoters to amplify the existing transcriptional program rather than activate new targets (PMID:20434984, PMID:23021215). Its biosynthetic output extends beyond Pol II: c-Myc and Max localize to nucleoli, associate with rDNA, recruit the TRRAP coactivator, and drive RNA Pol I transcription in a Pol II-independent manner (PMID:15723053), and c-Myc additionally has a transcription-independent role at the pre-replicative complex, localizing to early replication sites and promoting origin firing, with overexpression causing replication-associated DNA damage (PMID:17597761). Through defined targets, c-Myc activates the miR-17-92 cluster (creating a feed-forward loop with E2F1), ornithine decarboxylase, AP4 (which represses p21), and TAZ, the last being required to suppress c-Myc-induced apoptosis during hepatocarcinogenesis (PMID:15944709, PMID:8297793, PMID:19270520, PMID:34464659); c-Myc-induced apoptosis itself is mediated through p53 stabilization (PMID:8091232). c-Myc protein abundance is governed by a phosphorylation-dependent degron in which S62 phosphorylation stabilizes and T58 phosphorylation destabilizes the protein, controlling FBXW7-type ubiquitination; this is tuned by Pim and IKKα kinases that favor S62 over T58 phosphorylation, by PP2A holoenzymes that dephosphorylate either site, by SUMOylation (reversed by SENP1), and by multiple deubiquitinases and alternative E3 ligases (PMID:18438430, PMID:33461590, PMID:29535359, PMID:24927563, PMID:30305424, PMID:38218970, PMID:27009366, PMID:25944903). Upstream, c-MYC transcription is activated by Wnt/β-catenin/Tcf-4 and PDGF/Src/Vav2/Rac signaling and repressed by TGF-β/Smad3, C/EBPα, and its own negative autoregulation, integrating c-Myc levels into differentiation decisions (PMID:9727977, PMID:11389443, PMID:11689553, PMID:11340171, PMID:2182320).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1990 High

    Established that c-Myc controls its own abundance at the transcriptional level, defining negative autoregulation as a homeostatic constraint on Myc dosage.

    Evidence Transfection of activated c-myc with nuclear run-on transcription assays and dose-response analysis

    PMID:2182320

    Open questions at the time
    • Identity of the additional trans-acting factors required was not defined
    • Did not establish direct DNA binding by Myc at its own promoter
  2. 1994 High

    Resolved how c-Myc couples proliferation to apoptosis by showing the death output requires p53, separating Myc's cell-cycle and apoptotic functions.

    Evidence Conditional MycER activation in isogenic p53-null vs. wild-type fibroblasts with apoptosis and cell-cycle readouts

    PMID:8091232

    Open questions at the time
    • Molecular route from Myc to p53 stabilization not defined
    • Did not address which Myc target genes mediate the apoptotic signal
  3. 1998 High

    Connected c-MYC to a major oncogenic signaling axis by identifying it as a Wnt/β-catenin/Tcf-4 transcriptional target repressed by APC.

    Evidence Promoter reporter assays with Tcf-4 site mutations and reciprocal APC/β-catenin manipulation

    PMID:9727977

    Open questions at the time
    • Did not address cofactor requirements at the c-MYC promoter
    • Cell-type dependence of this regulation not mapped
  4. 2003 High

    Defined the genomic logic of Myc binding by showing it prefers E-boxes in CpG islands already in an open, acetylated chromatin state and further increases acetylation there.

    Evidence Quantitative ChIP in live human cells with bioinformatic E-box selection and histone acetylation ChIP

    PMID:12695333

    Open questions at the time
    • Did not establish how chromatin state is read to select sites
    • Functional consequence of binding for transcription not directly measured here
  5. 2005 High

    Extended Myc function beyond Pol II by demonstrating direct activation of Pol I-dependent rDNA transcription in nucleoli, linking Myc to ribosome biogenesis.

    Evidence Co-IP, ChIP at rDNA, siRNA, MycER with Pol II inhibition, and in situ proximity ligation

    PMID:15723053

    Open questions at the time
    • Mechanism of Myc recruitment to rDNA not defined
    • Relative contribution of Pol I vs Pol II activity to growth not quantified
  6. 2005 High

    Revealed a non-coding-RNA arm of Myc regulation by showing direct activation of the miR-17-92 cluster, which dampens E2F1 translation in a feed-forward loop.

    Evidence ChIP, reporter assays, and miRNA functional assays

    PMID:15944709

    Open questions at the time
    • Did not map the full target set of the cluster in this context
    • Physiological balance of E2F1 activation vs repression not quantified
  7. 2007 High

    Uncovered a transcription-independent function: c-Myc engages the pre-replicative complex and drives replication initiation, explaining replication stress upon overexpression.

    Evidence Co-IP with pre-RC components, replication-site localization, and siRNA depletion in mammalian cells and Xenopus cell-free extracts lacking transcription

    PMID:17597761

    Open questions at the time
    • Direct binding partner within the pre-RC not pinned down
    • Whether this function is genetically separable from transcription in vivo not established
  8. 2007 High

    Identified a ribosome-to-Myc feedback circuit by showing ribosomal protein L11 binds MBII, displaces TRRAP, and restrains Myc activity.

    Evidence Reciprocal co-IP, ChIP with histone acetylation readout, siRNA and overexpression with proliferation assays

    PMID:17599065

    Open questions at the time
    • Stoichiometry of L11 vs TRRAP competition in vivo not defined
    • Scope of target genes affected not genome-wide mapped
  9. 2010 High

    Clarified the core transcriptional mechanism by showing Myc acts mainly through pause release of Pol II rather than Pol II recruitment.

    Evidence Pol II ChIP-seq, GRO-seq, and genetic manipulation of Myc levels

    PMID:20434984

    Open questions at the time
    • Direct pause-release effector recruited by Myc not identified here
    • Did not address gene-selectivity of the pause-release effect
  10. 2012 High

    Reframed oncogenic Myc action by showing that at high levels it amplifies the existing active program genome-wide rather than activating a distinct target set.

    Evidence ChIP-seq and global transcriptome profiling in high vs normal Myc tumor cells

    PMID:23021215

    Open questions at the time
    • Did not reconcile amplification model with selective target activation at physiologic levels
    • Determinants of which active genes are amplified not fully defined
  11. 2016 High

    Defined the canonical degron logic and a circadian E3 input by showing CRY2-FBXL3 recognizes T58-phosphorylated Myc, with CRY1 unable to substitute.

    Evidence Co-IP, ubiquitylation assays, phospho-T58 dependency, and CRY1/CRY2 paralog comparison

    PMID:27840026

    Open questions at the time
    • In vivo contribution relative to FBXW7 not quantified
    • Circadian dynamics of Myc turnover not directly measured
  12. 2018 High

    Showed that SUMOylation status feeds into Myc stability, with SENP1 deSUMOylating Myc to stabilize it and promote S62 phosphorylation.

    Evidence In vitro deSUMOylation, co-IP, SENP1 catalytic mutant (C603S), and ubiquitination assays

    PMID:30305424

    Open questions at the time
    • SUMO acceptor lysines on Myc not defined in this entry
    • Crosstalk ordering between SUMO and phospho-degron not resolved
  13. 2018 High

    Demonstrated phosphatase-level control of the degron by showing Eya3 redirects PP2A-B55α to dephosphorylate pT58 (stabilizing), opposite to PP2A-B56α at pS62.

    Evidence Co-IP, phosphatase activity assays, phospho-specific immunoblotting, and xenograft metastasis model

    PMID:29535359

    Open questions at the time
    • Determinants of holoenzyme site-selectivity not fully defined
    • Generality across tissues beyond the metastasis model not established
  14. 2021 High

    Added a kinase that biases the degron toward stability by showing IKKα phosphorylates S67/S71 to reduce T58 phosphorylation and slow turnover.

    Evidence In vitro kinase assay, FRET, CRISPR IKKα knockout, cycloheximide chase, and phosphomimetic/non-phosphorylatable mutants

    PMID:33461590

    Open questions at the time
    • Upstream signals activating IKKα toward Myc not defined here
    • Interplay with GSK3β at T58 not kinetically resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the many opposing stability inputs (phosphorylation, SUMOylation, multiple E3 ligases and DUBs) are integrated in a single cell to set Myc level and target output in a context-specific way remains unresolved.
  • No unified quantitative model integrating degron PTMs with the amplification vs selective-activation transcriptional modes
  • Tissue-specific dominance of individual regulators not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0003677 DNA binding 2 GO:0042393 histone binding 2
Localization
GO:0005634 nucleus 3 GO:0005730 nucleolus 1
Pathway
R-HSA-392499 Metabolism of proteins 8 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-69306 DNA Replication 2
Partners
CRY2FBXW7MAXRPL11RPS14SENP1TRRAPYY1
Complex memberships
Myc-Maxpre-replicative complex (association)

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 c-MYC is a transcriptional target of the APC/beta-catenin/Tcf-4 signaling pathway; wild-type APC represses c-MYC expression while beta-catenin activates it through Tcf-4 binding sites in the c-MYC promoter. Reporter assay with Tcf-4 binding site mutations, expression manipulation of APC and beta-catenin Science High 9727977
2005 c-Myc directly binds and activates transcription of the miR-17-92 miRNA cluster on human chromosome 13 (confirmed by ChIP); two members of this cluster, miR-17-5p and miR-20a, negatively regulate translation of E2F1, revealing a feed-forward loop in which c-Myc simultaneously activates E2F1 transcription and limits its translation. Chromatin immunoprecipitation (ChIP), reporter assay, miRNA functional assays Nature High 15944709
2012 In tumor cells with elevated c-Myc, the protein accumulates at promoters of already-active genes and causes transcriptional amplification (increased output of the existing gene expression program) rather than activating a new set of target genes. ChIP-seq, global transcriptome profiling, comparison of high vs. normal c-Myc expressing tumor cells Cell High 23021215
2010 c-Myc promotes gene expression primarily by stimulating release of promoter-proximally paused RNA polymerase II (Pol II) rather than by recruiting Pol II to promoters. ChIP-seq for Pol II pausing, GRO-seq, genetic manipulation of c-Myc levels Cell High 20434984
2007 c-Myc has a direct, non-transcriptional role in DNA replication: it interacts with the pre-replicative complex, localizes to early replication sites, and is required for replication initiation in mammalian cells and Xenopus cell-free extracts. Overexpression increases origin firing, causing DNA damage and checkpoint activation. Co-immunoprecipitation with pre-RC components, localization to replication sites, siRNA depletion in mammalian cells and Xenopus cell-free extract (devoid of RNA transcription) Nature High 17597761
2005 c-Myc and Max interact in nucleoli, associate with ribosomal DNA, and c-Myc recruits TRRAP cofactor, enhances histone acetylation at rDNA, and activates RNA polymerase I transcription in response to mitogenic signals; this activity is separable from Pol II-dependent transcription. Co-immunoprecipitation, ChIP, siRNA knockdown, MycER system with Pol II inhibition, in situ proximity ligation Nature Cell Biology High 15723053
1994 c-Myc-induced apoptosis is mediated by p53: activation of c-Myc in quiescent wild-type p53 fibroblasts induces apoptosis and stabilizes p53, whereas p53-null fibroblasts undergo cell cycle re-entry but not apoptosis upon c-Myc activation. Conditional c-Myc activation (estrogen receptor fusion), p53-null vs. wild-type fibroblast comparison, apoptosis and cell cycle assays Science High 8091232
2003 c-Myc binds preferentially to E-box elements (CACGTG) located within CpG islands at promoters in live human cells; these high-affinity sites correlate with an open, pre-acetylated chromatin state and Myc further enhances histone acetylation at these loci. Quantitative ChIP with bioinformatics selection of E-box-containing promoters; histone acetylation ChIP Genes & Development High 12695333
2007 Ribosomal protein L11 (a c-Myc transcriptional target) binds to Myc box II (MBII) of c-Myc, competes with the coactivator TRRAP for this site, reduces histone H4 acetylation at c-Myc target gene promoters, and thereby inhibits c-Myc transcriptional activity and cell proliferation in a negative feedback loop. Co-immunoprecipitation, ChIP, siRNA knockdown, overexpression, cell proliferation assays The EMBO Journal High 17599065
1990 c-Myc protein negatively autoregulates its own transcription: introduction of activated c-myc suppresses endogenous c-myc expression at the level of transcriptional initiation in a concentration-dependent manner requiring additional trans-acting factors. Transfection of activated c-myc constructs, nuclear run-on transcription assays, dose-response analysis The EMBO Journal High 2182320
2016 CRY2, acting as a component of an FBXL3-containing E3 ubiquitin ligase complex, recruits T58-phosphorylated c-MYC for ubiquitylation and degradation; CRY1 cannot substitute for CRY2 in this function. Co-immunoprecipitation, ubiquitylation assays, CRY1/CRY2 genetic and biochemical comparison, phospho-T58 dependency experiments Molecular Cell High 27840026
2008 Pim-1 and Pim-2 kinases stabilize c-Myc by phosphorylating it at Ser329 (Pim-2 more directly) and by promoting decreased T58 phosphorylation with increased S62 phosphorylation (Pim-1), thereby inhibiting proteasomal degradation and enhancing c-Myc transcriptional activity. In vivo phosphorylation assays, site-directed mutagenesis (Ser329, Thr58, Ser62), pulse-chase protein stability, siRNA knockdown, transcriptional reporter assays Oncogene High 18438430
2001 C/EBPα negatively regulates c-Myc expression through an E2F binding site in the c-myc promoter; stable expression of c-Myc from an exogenous promoter not responsive to C/EBPα blocks myeloid differentiation, establishing that C/EBPα-mediated repression of c-Myc is required for granulocytic differentiation. Promoter mapping, representational difference analysis, oligonucleotide microarray, inducible C/EBPα cell system, stable c-Myc overexpression from exogenous promoter Molecular and Cellular Biology High 11340171
2001 TGF-β signaling represses c-myc transcription via Smad3 and E2F-4 binding to a composite TIE/E2F element in the c-myc promoter; TGF-β reduces p300 co-immunoprecipitating with E2F-4 without displacing E2F-4 from DNA. Promoter reporter assays with TIE/E2F site mutations, EMSA, co-immunoprecipitation of Smad3, E2F-4, and p300 Journal of Biological Chemistry High 11689553
1991 c-Myc suppresses MyoD-initiated and myogenin-initiated skeletal muscle differentiation independently of the negative regulator Id, establishing c-Myc and Id as two independent negative regulators of myogenesis. Transient and stable cotransfection in NIH 3T3 cells; conditional c-Myc induction system; epistasis with MyoD, myogenin, and Id Molecular and Cellular Biology High 1850105
2018 SENP1 is a c-Myc deSUMOylating enzyme: it interacts with and deSUMOylates c-Myc in cells and in vitro; catalytically inactive SENP1 (C603S) fails to stabilize c-Myc. SUMOylation of c-Myc promotes its polyubiquitination and proteasomal degradation, while SENP1-mediated deSUMOylation stabilizes c-Myc and promotes its S62 phosphorylation. In vitro deSUMOylation assay, co-immunoprecipitation, SENP1 catalytic mutant (C603S), ubiquitination assay, siRNA knockdown PNAS High 30305424
2014 USP37 directly binds and deubiquitinates c-Myc in a DUB activity-dependent manner to stabilize it; USP37 overexpression increases c-Myc levels while USP37 depletion promotes c-Myc degradation. Co-immunoprecipitation, in vivo ubiquitination assay, DUB activity-dependent rescue experiments, siRNA knockdown, overexpression Oncogene Medium 25284584
2018 Eya3 directly interacts with the PP2A-B55α holoenzyme and redirects its phosphatase activity toward pT58 on c-Myc (dephosphorylating T58 to stabilize c-Myc), in contrast to PP2A-B56α which dephosphorylates pS62 to destabilize c-Myc; this Eya3-PP2A-B55α complex promotes metastasis. Co-immunoprecipitation, phosphatase assays, xenograft metastasis model, phospho-specific immunoblotting Nature Communications High 29535359
2015 FBXO32 (Atrogin-1) acts as an E3 ubiquitin ligase that targets c-Myc for proteasomal degradation via ubiquitination at lysine 326; this regulation is independent of T58/S62 phosphorylation status. FBXO32 is itself a direct transcriptional target of c-Myc, forming a negative feedback loop. Ubiquitination assay, K326 mutagenesis, co-immunoprecipitation, reporter assay, siRNA knockdown/overexpression Journal of Biological Chemistry High 25944903
2016 ELL functions as a novel E3 ubiquitin ligase targeting c-Myc for proteasomal degradation, using UbcH8 as the ubiquitin-conjugating enzyme; cysteine 595 is the active site (C595A mutation abolishes ubiquitination and degradation of c-Myc). In vivo ubiquitination assay, active-site mutagenesis (C595A), co-immunoprecipitation, xenograft tumor assays Nature Communications High 27009366
2013 Ribosomal protein S14 (RPS14) interacts with the MBII and bHLH-LZ domains of c-Myc, inhibits c-Myc transcriptional activity by preventing recruitment of c-Myc and TRRAP to target gene promoters, and promotes c-Myc mRNA degradation through an Ago2/miRNA-dependent pathway. Co-immunoprecipitation (domain mapping), ChIP, siRNA knockdown, luciferase reporter assay Journal of Biological Chemistry Medium 23775087
1993 c-Myc directly induces expression and enzymatic activity of ornithine decarboxylase (ODC) in a manner not requiring de novo protein synthesis, establishing ODC as a direct transcriptional target mediating c-Myc's cell cycle effects. Conditional MycER activation, ODC mRNA and enzymatic activity assays, cycloheximide treatment to exclude indirect effects Cell Growth & Differentiation Medium 8297793
2002 CK2 (casein kinase II) regulates c-Myc protein stability: pharmacological inhibition or antisense knockdown of CK2 accelerates proteasome-dependent c-Myc protein turnover, while CK2 overexpression increases c-Myc levels. CK2 inhibitor treatment, sense/antisense CK2 transfection, proteasome inhibitor epistasis, protein stability assays Oncogene Medium 12149649
2001 PDGF stimulates c-myc promoter activity and expression through a Src-dependent, Ras/MAPK-independent pathway involving Vav2 activation of Rac GTPase. c-myc promoter reporter assay, dominant-negative constructs for Ras, MEK, Src, Vav2, and Rac; epistasis analysis Nature Cell Biology Medium 11389443
1996 Endogenous c-Myc and YY1 associate in vivo; c-Myc inhibits YY1 transcriptional activity not by blocking YY1 DNA binding but by interfering with YY1's ability to contact basal transcription factors TBP and TFIIB. Co-immunoprecipitation of endogenous proteins, gel shift assays for DNA binding, protein-protein interaction assays with TBP and TFIIB PNAS Medium 8855231
2009 c-Myc overexpression accelerates S-phase progression; WRN helicase is required to prevent replication-associated DNA damage in c-Myc-overexpressing cells, as WRN depletion in this context activates ATR-CHK1-CHK2-p53 replication stress signaling and induces senescence rescued by p53 loss. BrdU incorporation (S-phase timing), WRN siRNA depletion, DNA damage markers (γH2AX at replication sites), pathway inhibition, p53 knockdown rescue PLoS One Medium 19554081
2006 c-Myc overexpression causes anaplastic histopathology in medulloblastoma xenografts, with increased nuclear size, macronucleoli, and elevated indices of proliferation and apoptosis, establishing a causal link between c-Myc and anaplasia. Stable c-Myc overexpression in medulloblastoma cell lines, subcutaneous xenograft in nude mice, histopathological analysis, proliferation/apoptosis indices Cancer Research Medium 16423996
2009 c-MYC directly induces transcription of the AP4 transcription factor, which then represses p21 (CDKN1A) by binding elements near its promoter, thereby interfering with p21 induction by the DNA damage/p53 and TGFβ/Smad pathways. ChIP, reporter assay, AP4 overexpression/knockdown, epistasis with p53 and TGFβ pathways Cell Cycle Medium 19270520
2021 IKKα binds c-Myc and phosphorylates it at serines 67 and 71; this phosphorylation stabilizes c-Myc by reducing T58 phosphorylation (the GSK3β target) and consequent polyubiquitination. Phosphomimetic S67D/S71D c-Myc mutants show slower turnover and increased proliferative activity. Co-immunoprecipitation, FRET microscopy, in vitro kinase assay, cycloheximide chase, CRISPR/Cas9 IKKα knockout, phosphomimetic and non-phosphorylatable mutants Molecular Cancer High 33461590
2006 c-Myc aberrant stabilization in leukemia cell lines correlates with abnormal phosphorylation at T58 and S62 and decreased affinity for GSK3β (the kinase that phosphorylates T58 to trigger degradation), establishing deregulation of the T58/S62 phosphorylation-dependent degradation pathway as a mechanism of c-Myc overexpression in leukemia. Protein stability (pulse-chase), phospho-specific immunoblotting, GSK3β binding assay, sequencing for c-myc mutations Leukemia Medium 16855632
2009 Nickel compounds and hypoxia degrade c-Myc protein via the 26S proteasome through two mechanisms: (1) increased T58 phosphorylation leading to Fbw7-mediated ubiquitination, and (2) decreased levels of the deubiquitinase USP28 (via transcriptional repression through H3K9 dimethylation and protein degradation), both increasing net c-Myc ubiquitination. Proteasome inhibitor epistasis, phospho-T58 immunoblotting, USP28 siRNA knockdown, chromatin modification ChIP at USP28 promoter, HIF knockdown epistasis PLoS One Medium 20046830
2014 PP2A dephosphorylates c-MYC at serine 62 (S62) to destabilize it; endogenous PP2A inhibitors SET and CIP2A maintain S62 phosphorylation and c-MYC activity in breast cancer; SET antagonist OP449 decreases S62-pMYC and reduces tumorigenic potential. siRNA knockdown of SET/CIP2A, pharmacological PP2A activation (OP449), phospho-S62 immunoblotting, in vitro and in vivo tumor assays PNAS Medium 24927563
2014 TAZ is a direct transcriptional target of c-MYC; TAZ is required to prevent c-Myc-induced hepatocyte apoptosis during tumor initiation; conditional Taz knockout (but not Yap knockout) completely prevents c-Myc-driven hepatocarcinogenesis and causes tumor regression. Conditional knockout mice (Taz, Yap, Yap;Taz), ChIP for c-MYC at TAZ promoter, inducible TTR-CreERT2 system, tumor histology Journal of Hepatology High 34464659
1995 c-Myc protein (complexed with myn/Max) binds to the transcription initiator elements of lambda 5 and TdT promoters and represses their transcriptional activity when c-Myc is overexpressed. Gel retardation (EMSA), supershift with c-Myc and Max antibodies, cotransfection reporter assay with initiator mutations Nucleic Acids Research Medium 7870572
2024 USP43 deubiquitinates c-Myc at K148 and K289 in a DUB activity-dependent manner to stabilize it, and also competes with FBXW7 for access to c-Myc; this creates a USP43/c-Myc positive feedback loop promoting glycolysis and bladder cancer progression. siRNA library screen, co-immunoprecipitation, in vivo ubiquitination assay, site-directed mutagenesis (K148, K289), FBXW7 competition assay Cell Death & Disease Medium 38218970

Source papers

Stage 0 corpus · 100 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.) 4050 9727977
2005 c-Myc-regulated microRNAs modulate E2F1 expression. Nature 2311 15944709
2012 Transcriptional amplification in tumor cells with elevated c-Myc. Cell 1237 23021215
2010 c-Myc regulates transcriptional pause release. Cell 1060 20434984
2006 The c-Myc target gene network. Seminars in cancer biology 966 16904903
2002 c-MYC: more than just a matter of life and death. Nature reviews. Cancer 938 12360279
2003 Genomic targets of the human c-Myc protein. Genes & development 804 12695333
1994 Mediation of c-Myc-induced apoptosis by p53. Science (New York, N.Y.) 739 8091232
2012 c-Myc and cancer metabolism. Clinical cancer research : an official journal of the American Association for Cancer Research 646 23071356
2007 Non-transcriptional control of DNA replication by c-Myc. Nature 540 17597761
1984 Expression of c-myc changes during differentiation of mouse erythroleukaemia cells. Nature 424 6462247
2008 Apoptotic signaling by c-MYC. Oncogene 412 18955973
2005 c-Myc associates with ribosomal DNA and activates RNA polymerase I transcription. Nature cell biology 391 15723053
2001 Translocations involving c-myc and c-myc function. Oncogene 372 11607812
1999 Mechanisms of apoptosis by c-Myc. Oncogene 372 10378693
2021 Taking the Myc out of cancer: toward therapeutic strategies to directly inhibit c-Myc. Molecular cancer 314 33397405
2004 The life cycle of C-myc: from synthesis to degradation. Cell cycle (Georgetown, Tex.) 309 15467447
1999 The role of c-myc in cellular growth control. Oncogene 305 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 284 9558477
2000 c-Myc in breast cancer. Endocrine-related cancer 282 11021963
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
2000 N-myc can functionally replace c-myc in murine development, cellular growth, and differentiation. Genes & development 254 10837031
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 224 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
1999 Mysterious liaisons: the relationship between c-Myc and the cell cycle. Oncogene 195 10378690
2002 The proto-oncogene c-myc in hematopoietic development and leukemogenesis. Oncogene 192 12032779
1991 c-myc inhibition of MyoD and myogenin-initiated myogenic differentiation. Molecular and cellular biology 179 1850105
2016 CRY2 and FBXL3 Cooperatively Degrade c-MYC. Molecular cell 172 27840026
2008 The c-myc promoter: still MysterY and challenge. Advances in cancer research 163 18037408
2007 Inhibition of c-Myc activity by ribosomal protein L11. The EMBO journal 163 17599065
1993 c-Myc induces the expression and activity of ornithine decarboxylase. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 163 8297793
1992 Function of the c-Myc oncoprotein. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 163 1521738
2014 Targeting c-MYC by antagonizing PP2A inhibitors in breast cancer. Proceedings of the National Academy of Sciences of the United States of America 159 24927563
2012 Addiction to c-MYC in multiple myeloma. Blood 141 22806891
2014 USP37 directly deubiquitinates and stabilizes c-Myc in lung cancer. Oncogene 134 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 124 20140016
2001 Regulation of c-myc expression by PDGF through Rho GTPases. Nature cell biology 123 11389443
2002 Functional interaction of protein kinase CK2 and c-Myc in lymphomagenesis. Oncogene 120 12149649
2008 Carrot and stick: HIF-alpha engages c-Myc in hypoxic adaptation. Cell death and differentiation 117 18188166
2008 Crosstalk between c-Myc and ribosome in ribosomal biogenesis and cancer. Journal of cellular biochemistry 114 18773413
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 106 24692190
2022 Target c-Myc to treat pancreatic cancer. Cancer biology & therapy 102 34978469
1993 Electroporation enhances c-myc antisense oligodeoxynucleotide efficacy. Nucleic acids research 102 8346033
2014 MicroRNAs as regulators and mediators of c-MYC function. Biochimica et biophysica acta 99 24727092
1991 c-myc oncoprotein function. Biochimica et biophysica acta 99 1751543
2015 Linc-RoR promotes c-Myc expression through hnRNP I and AUF1. Nucleic acids research 98 26656491
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
2006 c-myc overexpression causes anaplasia in medulloblastoma. Cancer research 93 16423996
2005 c-myc expression: keep the noise down! Molecules and cells 89 16267388
2008 c-Myc: linking transformation and genomic instability. Current molecular medicine 88 18781952
1995 c-myc in vasculoproliferative disease. Circulation research 85 7834827
2014 Frequent coamplification and cooperation between C-MYC and PVT1 oncogenes promote malignant pleural mesothelioma. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 84 24926545
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 78 30305424
2016 C-myc overexpression drives melanoma metastasis by promoting vasculogenic mimicry via c-myc/snail/Bax signaling. Journal of molecular medicine (Berlin, Germany) 76 27543492
2006 Aberrant stabilization of c-Myc protein in some lymphoblastic leukemias. Leukemia 76 16855632
2018 Eya3 partners with PP2A to induce c-Myc stabilization and tumor progression. Nature communications 74 29535359
1996 YY1 and c-Myc associate in vivo in a manner that depends on c-Myc levels. Proceedings of the National Academy of Sciences of the United States of America 73 8855231
2020 FBXL6 governs c-MYC to promote hepatocellular carcinoma through ubiquitination and stabilization of HSP90AA1. Cell communication and signaling : CCS 72 32576198
2013 Ribosomal protein S14 negatively regulates c-Myc activity. The Journal of biological chemistry 72 23775087
2009 c-Myc accelerates S-phase and requires WRN to avoid replication stress. PloS one 70 19554081
2016 Therapeutic aspects of c-MYC signaling in inflammatory and cancerous colonic diseases. World journal of gastroenterology 68 27672289
2006 c-Myc overexpression and endocrine resistance in breast cancer. The Journal of steroid biochemistry and molecular biology 68 17052904
2024 USP43 stabilizes c-Myc to promote glycolysis and metastasis in bladder cancer. Cell death & disease 65 38218970
2014 Attacking c-Myc: targeted and combined therapies for cancer. Current pharmaceutical design 65 25341931
2015 FBXO32 Targets c-Myc for Proteasomal Degradation and Inhibits c-Myc Activity. The Journal of biological chemistry 64 25944903
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
1990 C-MYC: evidence for multiple regulatory functions. Seminars in cancer biology 58 2133113
2004 Of mice and Myc: c-Myc and mammary tumorigenesis. Journal of mammary gland biology and neoplasia 52 15082916
2015 Integrin α1β1 expression is controlled by c-MYC in colorectal cancer cells. Oncogene 51 26096932
2021 TAZ is indispensable for c-MYC-induced hepatocarcinogenesis. Journal of hepatology 50 34464659
1998 Expression of the c-Myc protein in childhood medulloblastoma. Journal of pediatric hematology/oncology 50 9482408
1992 Antisense c-myc oligodeoxyribonucleotide cellular uptake. Pharmaceutical research 49 1384028
2009 Mechanisms of c-myc degradation by nickel compounds and hypoxia. PloS one 48 20046830
2008 How the c-myc promoter works and why it sometimes does not. Journal of the National Cancer Institute. Monographs 45 18648001
1987 Effect of 4-hydroxynonenal on c-myc expression. Toxicologic pathology 45 3475758
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
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 41 32817420
1995 The c-myc protein represses the lambda 5 and TdT initiators. Nucleic acids research 41 7870572
2006 c-Myc inhibition negatively impacts lymphoma growth. Journal of pediatric surgery 40 16410134
2016 ELL targets c-Myc for proteasomal degradation and suppresses tumour growth. Nature communications 38 27009366
2023 The DUBA-SLC7A11-c-Myc axis is critical for stemness and ferroptosis. Oncogene 36 37537342
2021 The inflammatory kinase IKKα phosphorylates and stabilizes c-Myc and enhances its activity. Molecular cancer 36 33461590
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
2022 SLCO4A1-AS1 promotes colorectal tumourigenesis by regulating Cdk2/c-Myc signalling. Journal of biomedical science 34 35039060
2018 Artemisitene suppresses tumorigenesis by inducing DNA damage through deregulating c-Myc-topoisomerase pathway. Oncogene 34 29795406
2014 Repression of PLA2R1 by c-MYC and HIF-2alpha promotes cancer growth. Oncotarget 34 24657971

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