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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
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