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FLASH GENE
Symbol MYC contributors: shn/ - updated : 08-07-2020
HGNC name v-myc myelocytomatosis viral oncogene homolog (avian)
HGNC id 7553
Corresponding disease
MYC Burkitt lymphoma/acute lymphoblastic leukemia
Location 8q24.21      Physical location : 128.748.314 - 128.753.678
Synonym name
  • oncogene myc
  • myc proto-oncogene protein
  • transcription factor p64
  • v-myc avian myelocytomatosis viral oncogene homolog
  • avian myelocytomatosis viral oncogene homolog
  • protooncogene homologous to myelocytomatosis virus
  • transcription factor p64
    • Synonym symbol(s) c-MYC, bHLHe39, MRTL
    DNA
    TYPE functioning gene
    STRUCTURE 5.36 kb     3 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   transcription factor
    motif
    text structure
  • two binding site for DLX5 transcription factor in the promoter (Xu 2009)
    • MAPPING cloned Y linked Y status confirmed
    Map cen - D8S1128 - D8S1813 - MYC MYC - D8S1720 - D8S263 - qter
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 splicing 2379 65 454 - 1984 6463648
    3 - 1023 - 170 - -
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivemouth   highly
    Urinarybladder   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N terminus transactivating domain
  • a nuclear localization signal (NLS)
  • a basic helix-loop-helix (HLH) domain
  • a leucine zipper domain interacting with SMARCB1
  • C-terminal region counteracts the inhibitory activity of TERF1 and participates in the regulation of telomere length
  • c-ter of Myc protein contains a basic region helix-loop-helix leucine zipper motif (bHLH-Zip), which has DNA-binding activity
    • conjugated RiboP
    HOMOLOGY
    interspecies ortholog to Myc, Mus musculus
    ortholog to Myc, Rattus norvegicus
    ortholog to myca, Danio rerio
    Homologene
    FAMILY
    CATEGORY transcription factor , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,microfilament
    intracellular,nucleus
    basic FUNCTION
  • plays a role in cell cycle progression, apoptosis, cellular transformation and functions as a transcription factor
  • regulates expression of numerous target genes controlling key cellular functions, including cell growth and cell cycle progression and has a critical role in DNA replication
  • stimulating genes required for proliferation and cell cycle regulation, through the induction of CDK4
  • also inducing apoptosis in sensitive cells
  • acts in the development, proliferation, and survival of lymphocytes
  • c-Myc promotes vascular and hematopoietic development, by functioning as a master regulator of angiogenic factors
  • critical mediator of the early stages of neoplasia following APC loss
  • may be involved in the regulation of telomere length through its direct binding with TERF1
  • employs TFAP4 to maintain cells in a proliferative, progenitor-like state
  • critical mediator of the early stages of neoplasia following APC loss
  • regulates the expression of several components of the protein synthetic machinery, including ribosomal proteins, initiation factors of translation, RNA polymerase III and ribosomal DNA
  • represses the transcription of the TGFb-activated genes
  • Myc and TGFb signaling may cooperate in promoting epithelial-to-mesenchymal transition (EMT) and metastasis in carcinomas
  • upregulates PTBP1, HNRNPA1 and HNRNPA2B1 and alters PKM2 splicing
  • required to allow the interaction of the E2F1 protein with the E2F gene promoters
  • switch from MNT to MYC during bile duct ligation is responsible for the induction in TP53 and cyclin D1 expression and contributes to apoptosis
  • promotes proliferation by stabilizing the mitotic spindle in fast-dividing cells via NSUN2 and NUSAP1
  • in association with RPL11, inhibits the binding of TRRAP to the 5S rRNA and tRNA genes
  • plays a major role in Pol II pause release during transcription
  • critical for cell homeostasis and growth but is a potent oncogenic factor if improperly regulated
  • ability to form a repressive complex with ZBTB17 transcription factor is important to induce and maintain lymphomagenesis
  • key role for the MYC-MAX-MXD1 network in the development and progression of neural crest tumors
  • oncoprotein playing critical roles in multiple biological processes by controlling cell proliferation, apoptosis, differentiation, and metabolism
  • MYC and CDX2 mediate E-selectin ligand expression in colon cancer cells undergoing EGF/FGF2-induced epithelial–mesenchymal transition
  • KLF1, KLF2, and MYC control a regulatory network essential for embryonic erythropoiesis
  • is not an on-off specifier of a particular transcriptional program, but is a universal amplifier of gene expression increasing output at all active promoters
  • MYC may influence RNA levels by modulating rates of synthesis or degradation directly or indirectly aside from controlling pause release
  • vitamin D and VDR regulate the MYC/MXD1 network to suppress MYC function, providing a molecular basis for cancer preventive actions of vitamin D
  • PTEN and MYC exist in homeostatic balance to control normal growth, which is disrupted in cancer cells c
  • functional link between EYA1, SIX2, and MYC in driving the expansion and maintenance of the multipotent progenitors during nephrogenesis
  • antagonistic roles of the SMARCB1 and MYC transcriptional regulators in mediating cellular and oncogenic functions
    • CELLULAR PROCESS cell life, proliferation/growth
    cell life, cell death/apoptosis
    nucleotide, replication
    nucleotide, transcription
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling
    a component
  • forms a specific DNA-binding complex with a partner protein termed MAX
  • part of the MYC-MAX-MXD1 network
  • FUBP1-FUSE complex is an essential component of a transcription molecular machinery that is necessary for tight regulation of expression of many key genes including MYC and CDKN1A
    • INTERACTION
    DNA regulates the expression of TFAP4 via CACGTG motifs in the first intron of the TFAP4 gene (induction of TFAP4 was required for c-MYC-mediated cell cycle reentry of anti-estrogen arrested breast cancer cells and mitogen-mediated repression of the CDKN1A)
  • p21(WAF1/CIP1) promoter
  • EMT-associated gene Snail promoter
    • RNA mina53 (Myc-induced nuclear antigen with a molecular mass of 53 kDa)
  • transcription factor E2F1
    • small molecule
    protein
  • actin-related protein BAF53
  • cyclin T1, BRCA1, CDC6
  • corepressor Dnmt3a
  • TATA binding protein (TBP)
  • TRRAP, GCN5, TIP60 histone acetyltransferase complex
  • MAP kinase MAP2K1
  • c-Jun N-terminal kinase
  • Helix-loop-helix zipper protein MAX
  • DNA mismatch repair proteins MLH1 and MSH2
  • Promyelocytic Leukaemia gene product PML
  • mina53 (Myc-induced nuclear antigen with a molecular mass of 53 kDa)
  • YY1, p107, Bin1
  • AMY-1 (Associate of C-MYC)
  • Pam (protein associated with Myc)
  • PARP-10 (poly(ADP-ribose) polymerase 10)
  • PDGF beta-receptor mRNA
  • A CCAAT box-binding protein subunit, CBF-C/NF-YC
  • Nmi, c-Raf kinase
  • pRb-related protein p107
  • RelA(p37)
  • Smad2 and Smad3
  • INI1/hSNF5
  • Sp1/Sp3
  • Transcription factor AP-2 beta
  • Guanine nucleotide exchange factor, Tiam1
  • tumor protein p73 (TP73)
  • TUBA1A, TUBA1B, TUBA3C, TUBA4A, TUBA8
  • Yin-Yang-1 (YY1)
  • POZ domain Zn finger protein (Miz-1; Myc-interacting Zn finger protein-1)
  • eIF-4E cooperates with c-Myc
  • MYC and MNT use MAX as a cofactor for DNA binding
  • MYC, directly induces TAF4B expression, through one of the non-canonical E-box sites, which is in a highly conserved region of TAF4B promoters
  • MYC, ZBTB17 and MAX are associated with the CEBPD promoter in proliferating cells, when CEBPD expression is repressed
  • binding of MYC to ZBTB17 is required to antagonize growth suppression and induction of senescence by TGFbeta
  • interacting with FBXW7 and IKBKG (interaction caused reduced ubiquitination of MYC by inhibiting ubiquitinating activity of FBXW7 without blocking the interaction between MYC and FBXW7)
  • NFE2L2 interacting with KRAS and MYC (KRAS and MYC oncogenes can constitutively increase the transcription of NFE2L2 to elevate the basal activity of the antioxidant and cellular detoxification program)
  • SIRT1 interacts physically with the C-terminus of MYC and deacetylates MYC
  • MYC protein, which is antagonized by MXI1, causes renal cystogenesis
  • GPC3 is a transcriptional target of MYC and the expression of MYC is also regulated by GPC3, thus forming a positive feedback signaling loop
  • CDCA7 associates with MYC and this association is modulated in a phosphorylation-dependent manner
  • STK38 regulates MYC protein stability and turnover in a kinase activity-dependent manner
  • SIRT2 enhanced MYCN and MYC protein stability and promoted cancer cell proliferation
  • effects of ASH2L in controlling open chromatin structure are manifested further by regulation of MYC and CHD7 expression
  • physical interaction with both NDN and CYS1 and the MYC P1 promoter, as well as between these proteins
  • EIF2AK2 influence the isoform and the level of expression of the proto-oncogene MYC
  • MYC regulated the expression of PDF, likely indirectly
  • MYC interacts with the human STAGA coactivator complex via multivalent contacts with the KAT2A and TRRAP subunits
  • KIF5B transports MYC for proteasomal degradation in the cytoplasm and the proper degradation of MYC mediated by KIF5B transport is important for transformation activities of MYC
  • SIN3B decreases MYC protein levels upon MYC deacetylation
  • TFAP4 is the transcription factor that was induced by MYC and sustained activation of antigen-specific CD8+ T cells
  • ERBB2, MYC, WIF1, RBM38, PTEN, are involved in the HOTAIR regulation network
  • EYA1 interacts with SIX2 and MYC to control self-renewing cell activity
  • PLD6 alters mitochondrial fusion and fission dynamics downstream of MYC
  • nucleolar USP36 is a novel MYC deubiquitinase that controls the end-point of MYC degradation pathway in the nucleolus
  • PIAS1 is a positive regulator of MYC
  • acute myeloid leukemia (AML) cells require the BRD9 subunit of the SWI-SNF chromatin-remodeling complex to sustain MYC transcription, rapid cell proliferation and a block in differentiation
  • balanced ubiquitination and deubiquitination of MYC by TRIM32 and USP7 is a novel mechanism for stem cell fate determination
  • dual role for MYC, as a major contributor in PKD1-induced cystogenesis and in a feed-forward regulatory PKD1-MYC loop mechanism that may also prevail in human ADPKD
  • SENP1 is a crucial MYC deSUMOylating enzyme that positively regulates MYC stability and activity
  • SLC1A5 is critical for activation of MTOR activity by amino acids, and is a transcriptional target of MYC
  • SMARCB1 also interacts with the oncoprotein transcription factor MYC and is proposed to stimulate MYC activity
  • interaction of MTA1 with MYC and recruitment of MTA1-MYC complex on to the LDHA promoter to regulate its transcription
    • non-small cell lung cancer
  • TRIM55 inhibits Colorectal tumor development via, at least in part, enhancing protein degradation of MYC
  • UPK1B enhanced the invasiveness and stem cell characteristics of non-small cell lung cancer by activating MYC/UPK1B axis
    • cell & other
  • interacting with various cellular factors including MAX, YY1, AMPHL for binding E box recognition sites
  • nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) stimulates c-MYC
    • REGULATION
    activated by AMY-1 (Associate of C-MYC)
    retinoblastoma 1 (RB1)
    inhibited by BRCA1
    repressed by MM-1
    increased expression of ELAVL1 by RBM38 leading to decreased expression of MYC and, subsequently, promotes RBM38-mediated growth suppression
    Other translation modulated by HNRPC in a cell-cycle dependent manner
    downregulated byHIV-1 gp120
    NCL may induce the formation of MYC G-quadruplex that functions as a transcriptional repressor
    phosphorylated by IKBKG
    deacetylation of MYC by SIRT1 promotes its association with MAX, a partner essential for its activation, thereby facilitating MYC transactivation activity on TERT promoter
    ASSOCIATED DISORDERS
    corresponding disease(s) MYC
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in small cell and non small cell lung carcinoma with poor prognosis and in prostate tumor (benign or carcinoma)
    tumoral       gain of function
    in hepatopcellular carcinoma
    tumoral     --other  
    abnormal expression of REST and MYC in neural stem/progenitor cells causes cerebellum-specific tumors by blocking neuronal differentiation and thus maintaining the "stemness" of these cells
    tumoral fusion translocation    
    t(8;9)(q24;p13), fusion to PAX5 on chromosome 9, joining MYC to ZCCHC7 and to ZBTB5 exon 2, two genes encoding zinc-finger proteins, in B-cells lymphomas
    constitutional     --over  
    Myc-overexpressing cells have cytokinesis defects, supernumery centrosomes and genomic instability as a consequence of augmented cap-dependent translation
    tumoral     --other  
    dysregulation by complex mechanisms is one of the major molecular events in the oncogenesis of plasma cell leukemia
    Susceptibility
  • to urinary bladder cancer
  • to prostate carcinoma
    • Variant & Polymorphism other polymorphisms increasing the risk of urinary bladder cancer
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductivebreast
    PIM2-USP27X-MYC signaling axis is a new potential target for breast cancer treatment
    cancer  
    transient inactivation of MYC may be an effective therapy for certain cancers
    ANIMAL & CELL MODELS
  • c-Myc-null mice die by embryonic day 10.5 with defects in growth and in cardiac and neural development
  • Myc-induced T cell leukemia in transgenic zebrafish
  • transgenic mice conditionally overexpress Myc in liver cells develop liver tumors and died
  • double-transgenic mice overexpress myc and EIF4E develop lymphoma