Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

MYC v-myc myelocytomatosis viral oncogene homolog (avian)

Identity

Other namesC-MYC
identified as the oncogene of the MC29 avian myelocytomatosis virus
HGNC (Hugo) MYC
LocusID (NCBI) 4609
Location 8q24.21
Location_base_pair Starts at 128748315 and ends at 128753680 bp from pter ( according to hg19-Feb_2009)  [Mapping]
 
  c-MYC (8q24) in normal cells: PAC 944B18 (top) and PAC 968N11 (below) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.

DNA/RNA

Transcription alternative splicing; coding sequences: 1318 and 1362 bp for proteins p64 and p67 respectively

Protein

Description 439 amino acids and 48 kDa in the p64; 454 amino acids in the p67 (15 additional amino acids in N-term; contains from N-term to C-term: a transactivation domain,an acidic domain, a nuclear localization signal, a basic domain, an helix-loop-helix motif, and a leucin zipper; DNA binding protein
Expression expressed in almost all proliferating cells in embryonic and adult tissues; in adult tissues, expression correlates with cell proliferation; abnormally high expression is found in a wide variety of human and rodent tumours
Localisation located predominantly in the nucleus
Function
  • The encoded myc oncoproteins are apparently transcription factors known as basic region-helixloop-helix-leucine zipper (b-HLH-Zip) proteins; like other b-HLH-Zip proteins, they modulate the expression of target genes by binding to specific DNA sequences
  • In this case, however, the binding requires dimerization to another b-HLH-Zip protein, namely Max (the latter can also form heterodimers with Mad as well as homodimers with itself). Myc/Max complexes activate transcription and promote cell proliferation and transformation. Mad/Max complexes, however, repress transcription and block myc-mediated cell transformation. All three complexes bind to the same DNA sequence and are competitors.
  • Expression of c-myc is required for proliferation; it can over-ride p53-induced Gl-arrest by inducing an inhibitor of the cyclin kinase inhibitor WAFI(p2l). The latter (located at 6p2l) normally coordinates S and M phases of the cell cycle. If absent, cells with damaged DNA arrest not in GI but in a G2-like state from which they can pass through additional S phases without intervening normal mitoses (the deformed polyploid cells that result may then die by apoptosis). The uncoupling of S and M may contribute to the acquisition of the chromosomal abnormalities manifested by most tumour cells when apoptotic pathways have been circumvented
  • Homology the human myc family also includes N-myc and L-myc, rather specifically implicated in neuroblastoma and small-cell lung carcinoma, respectively, in which amplified copy numbers have been found

    Implicated in

    Entity Burkitt's lymphoma
    Hybrid/Mutated Gene the gene is activated by translocation next to an immunoglobulin constant gene. Most frequently, it is positioned near the immunoglobulin heavy-chain (IgH) constant region on chromosome 14 but, in some tumours, near the light-chain region chromosome 2 (IgK) or 22 (IgL). It is now known that immunoglobulin joining enzymes may be involved in recombinations associated with a variety of chromosomal translocations in B and T cells
      
    Entity amplification has been described in many types of tumour, including breast, cervical and colon cancers, as well as in squamous cell carcinomas of the head and neck, myeloma, non-Hodgkin's lymphoma, gastric adenocarcinomas and ovarian cancer
    Prognosis C-myc involvement is by no means universally found in these cancers; there may be a correlation with the more advanced stages, suggesting a value as a prognostic indicator (although this has not been demonstrated in some studies for breast, ovarian and cervical cancers)
    Oncogenesis C-myc gene activation (enhanced expression and/or amplification) may result from chromosomal duplication as well as translocation, and from retroviral as well as point mutation. Multiple copies of the gene may be evidenced in homogeneously staining chromosomal regions and in double minutes
      
    Entity Role of c-myc in other conditions
    Disease In adult respiratory distress syndrome the degree of diffuse alveolar damage and consequently the prognosis may be related to the intensity of expression of c-myc in the alveolar cells which, if severe, may contribute to deregulation of cellular proliferation and apoptosis. In endometriosis, c-myc expression is a possibly important regulator of cellular proliferation.
      

    Breakpoints

     

    To be noted

    Although c-myc appears to be active in variety of tumours, it is important to realise that in common with other mechanistic pathways to cancer induction and progression no single genetic event (including c-myc deregulation) will prove to be necessary in the light of the inherent complexity and diversity of cellular pathways leading to neoplasia

    Other Leukemias implicated (Data extracted from papers in the Atlas)

    Leukemias 11q23ChildAMLID1615 11q23ID1030 11q23secondLeukID1131 t1119ELLID1029 t0812q24q22ID2057
    t0814ID1050 8p11inMPDID1091 inv8p11q13ID1189 PrimarCutanALCLID2118 t0708q34p11ID1409
    t0809p12q33ID1129 t0811p11p15ID1200 t0811p12p15ID1521 t0812p12p11ID1330 t0812p12q15ID1201
    t0817p12q23ID1387 t0817p12q25ID1202 t0819p11q13ID1315 t0819p12q13ID1203 t0822p11q11ID1224
    t0822p11q13ID1119 t0921q34q22ID1483

    Other Solid tumors implicated (Data extracted from papers in the Atlas)

    Solid Tumors AmeloblastomID5945 MedulloblastomaID5065 rhab5004 rhabID5004 blad5001
    bladID5001 colon5006 colonID5006 EmbryoRhabdomyoID5193 IrisHamartomaID5100
    OvaryEpithTumID5230 rhab5004 rhabID5004 SkinMelanomID5416 ConvOsteoID5344
    OvarianGermCellID5067 AlvRhabdomyosarcID5194

    External links

    Nomenclature
    HGNC (Hugo)MYC   7553
    Cards
    AtlasMYCID27
    Entrez_Gene (NCBI)MYC  4609  v-myc avian myelocytomatosis viral oncogene homolog
    GeneCards (Weizmann)MYC
    Ensembl (Hinxton)ENSG00000136997 [Gene_View]  chr8:128748315-128753680 [Contig_View]  MYC [Vega]
    ICGC DataPortalENSG00000136997
    cBioPortalMYC
    AceView (NCBI)MYC
    Genatlas (Paris)MYC
    WikiGenes4609
    SOURCE (Princeton)NM_002467
    Genomic and cartography
    GoldenPath (UCSC)MYC  -  8q24.21   chr8:128748315-128753680 +  8q24   [Description]    (hg19-Feb_2009)
    EnsemblMYC - 8q24 [CytoView]
    Mapping of homologs : NCBIMYC [Mapview]
    OMIM113970   190080   
    Gene and transcription
    Genbank (Entrez)AA807892 AK303921 AK312883 BC000141 BC000917
    RefSeq transcript (Entrez)NM_002467
    RefSeq genomic (Entrez)AC_000140 NC_000008 NC_018919 NG_007161 NT_008046 NW_001839136 NW_004929340
    Consensus coding sequences : CCDS (NCBI)MYC
    Cluster EST : UnigeneHs.202453 [ NCBI ]
    CGAP (NCI)Hs.202453
    Alternative Splicing : Fast-db (Paris)GSHG0029250
    Alternative Splicing GalleryENSG00000136997
    Gene ExpressionMYC [ NCBI-GEO ]     MYC [ SEEK ]   MYC [ MEM ]
    Protein : pattern, domain, 3D structure
    UniProt/SwissProtP01106 (Uniprot)
    NextProtP01106  [Medical]
    With graphics : InterProP01106
    Splice isoforms : SwissVarP01106 (Swissvar)
    Domaine pattern : Prosite (Expaxy)BHLH (PS50888)   
    Domains : Interpro (EBI)bHLH_dom [organisation]   Myc-LZ [organisation]   Tscrpt_reg_Myc [organisation]   Tscrpt_reg_Myc_N [organisation]  
    Related proteins : CluSTrP01106
    Domain families : Pfam (Sanger)HLH (PF00010)    Myc-LZ (PF02344)    Myc_N (PF01056)   
    Domain families : Pfam (NCBI)pfam00010    pfam02344    pfam01056   
    Domain families : Smart (EMBL)HLH (SM00353)  
    DMDM Disease mutations4609
    Blocks (Seattle)P01106
    PDB (SRS)1A93    1EE4    1MV0    1NKP    2A93    2OR9   
    PDB (PDBSum)1A93    1EE4    1MV0    1NKP    2A93    2OR9   
    PDB (IMB)1A93    1EE4    1MV0    1NKP    2A93    2OR9   
    PDB (RSDB)1A93    1EE4    1MV0    1NKP    2A93    2OR9   
    Human Protein AtlasENSG00000136997 [gene] [tissue] [antibody] [cell] [cancer]
    Peptide AtlasP01106
    HPRD01818
    IPIIPI00935431   IPI00033016   IPI00816223   IPI00977922   IPI00026900   IPI00425663   IPI00796046   IPI00973947   
    Protein Interaction databases
    DIP (DOE-UCLA)P01106
    IntAct (EBI)P01106
    FunCoupENSG00000136997
    BioGRIDMYC
    InParanoidP01106
    Interologous Interaction database P01106
    IntegromeDBMYC
    STRING (EMBL)MYC
    Ontologies - Pathways
    Ontology : AmiGOnegative regulation of transcription from RNA polymerase II promoter  MAPK cascade  RNA polymerase II core promoter proximal region sequence-specific DNA binding  RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription  branching involved in ureteric bud morphogenesis  positive regulation of mesenchymal cell proliferation  DNA binding  DNA binding  sequence-specific DNA binding transcription factor activity  protein binding  nucleus  nucleoplasm  nucleoplasm  nucleolus  spindle  energy reserve metabolic process  chromatin remodeling  transcription, DNA-templated  transcription initiation from RNA polymerase II promoter  cellular iron ion homeostasis  cellular response to DNA damage stimulus  cell cycle arrest  transforming growth factor beta receptor signaling pathway  Notch signaling pathway  transcription factor binding  positive regulation of cell proliferation  response to gamma radiation  gene expression  regulation of gene expression  oxygen transport  regulation of telomere maintenance  protein complex binding  negative regulation of stress-activated MAPK cascade  cellular response to UV  cellular response to drug  response to drug  negative regulation of apoptotic process  protein complex  positive regulation of cysteine-type endopeptidase activity involved in apoptotic process  fibroblast apoptotic process  negative regulation of monocyte differentiation  positive regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase II promoter  positive regulation of transcription from RNA polymerase II promoter  positive regulation of transcription from RNA polymerase II promoter  protein dimerization activity  positive regulation of fibroblast proliferation  positive regulation of fibroblast proliferation  negative regulation of fibroblast proliferation  positive regulation of epithelial cell proliferation  chromosome organization  negative regulation of cell division  canonical Wnt signaling pathway  repressing transcription factor binding  response to growth factor  E-box binding  positive regulation of metanephric cap mesenchymal cell proliferation  positive regulation of DNA biosynthetic process  positive regulation of response to DNA damage stimulus  
    Ontology : EGO-EBInegative regulation of transcription from RNA polymerase II promoter  MAPK cascade  RNA polymerase II core promoter proximal region sequence-specific DNA binding  RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription  branching involved in ureteric bud morphogenesis  positive regulation of mesenchymal cell proliferation  DNA binding  DNA binding  sequence-specific DNA binding transcription factor activity  protein binding  nucleus  nucleoplasm  nucleoplasm  nucleolus  spindle  energy reserve metabolic process  chromatin remodeling  transcription, DNA-templated  transcription initiation from RNA polymerase II promoter  cellular iron ion homeostasis  cellular response to DNA damage stimulus  cell cycle arrest  transforming growth factor beta receptor signaling pathway  Notch signaling pathway  transcription factor binding  positive regulation of cell proliferation  response to gamma radiation  gene expression  regulation of gene expression  oxygen transport  regulation of telomere maintenance  protein complex binding  negative regulation of stress-activated MAPK cascade  cellular response to UV  cellular response to drug  response to drug  negative regulation of apoptotic process  protein complex  positive regulation of cysteine-type endopeptidase activity involved in apoptotic process  fibroblast apoptotic process  negative regulation of monocyte differentiation  positive regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase II promoter  positive regulation of transcription from RNA polymerase II promoter  positive regulation of transcription from RNA polymerase II promoter  protein dimerization activity  positive regulation of fibroblast proliferation  positive regulation of fibroblast proliferation  negative regulation of fibroblast proliferation  positive regulation of epithelial cell proliferation  chromosome organization  negative regulation of cell division  canonical Wnt signaling pathway  repressing transcription factor binding  response to growth factor  E-box binding  positive regulation of metanephric cap mesenchymal cell proliferation  positive regulation of DNA biosynthetic process  positive regulation of response to DNA damage stimulus  
    Pathways : BIOCARTACTCF: First Multivalent Nuclear Factor [Genes]    MAPKinase Signaling Pathway [Genes]    Mechanism of Gene Regulation by Peroxisome Proliferators via PPARa(alpha) [Genes]    Overview of telomerase protein component gene hTert Transcriptional Regulation [Genes]    Role of EGF Receptor Transactivation by GPCRs in Cardiac Hypertrophy [Genes]    WNT Signaling Pathway [Genes]    Cadmium induces DNA synthesis and proliferation in macrophages [Genes]    Inhibition of Cellular Proliferation by Gleevec [Genes]    Telomeres, Telomerase, Cellular Aging, and Immortality [Genes]    Neuropeptides VIP and PACAP inhibit the apoptosis of activated T cells [Genes]    Erk1/Erk2 Mapk Signaling pathway [Genes]    IL-2 Receptor Beta Chain in T cell Activation [Genes]    p38 MAPK Signaling Pathway [Genes]    Tumor Suppressor Arf Inhibits Ribosomal Biogenesis [Genes]   
    Pathways : KEGGMAPK signaling pathway    ErbB signaling pathway    Cell cycle    PI3K-Akt signaling pathway    Wnt signaling pathway    TGF-beta signaling pathway    Hippo signaling pathway    Jak-STAT signaling pathway    Thyroid hormone signaling pathway    Hepatitis B    HTLV-I infection    Epstein-Barr virus infection    Pathways in cancer    Transcriptional misregulation in cancer    Proteoglycans in cancer    MicroRNAs in cancer    Colorectal cancer    Endometrial cancer    Thyroid cancer    Bladder cancer    Chronic myeloid leukemia    Acute myeloid leukemia    Small cell lung cancer   
    Protein Interaction DatabaseMYC
    Wikipedia pathwaysMYC
    Gene fusion - rearrangments
    Rearrangement : TICdbMYC [8q24.21]  -  - [10q23.33]
    Rearrangement : TICdb- [-]  -  MYC [5q31.1]
    Rearrangement : TICdbMIR142 [17q22]  -  MYC [3p25.1]
    Polymorphisms : SNP, mutations, diseases
    SNP Single Nucleotide Polymorphism (NCBI)MYC
    snp3D : Map Gene to Disease4609
    SNP (GeneSNP Utah)MYC
    SNP : HGBaseMYC
    Genetic variants : HAPMAPMYC
    Exome VariantMYC
    1000_GenomesMYC 
    ICGC programENSG00000136997 
    Cancer Gene: CensusMYC 
    Somatic Mutations in Cancer : COSMICMYC 
    CONAN: Copy Number AnalysisMYC 
    Mutations and Diseases : HGMDMYC
    Mutations and Diseases : intOGenMYC
    Genomic VariantsMYC  MYC [DGVbeta]
    dbVarMYC
    ClinVarMYC
    Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
    Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
    Diseases
    OMIM113970    190080   
    MedgenMYC
    GENETestsMYC
    Disease Genetic AssociationMYC
    Huge Navigator MYC [HugePedia]  MYC [HugeCancerGEM]
    General knowledge
    Homologs : HomoloGeneMYC
    Homology/Alignments : Family Browser (UCSC)MYC
    Phylogenetic Trees/Animal Genes : TreeFamMYC
    Chemical/Protein Interactions : CTD4609
    Chemical/Pharm GKB GenePA31353
    Drug Sensitivity MYC
    Clinical trialMYC
    Cancer Resource (Charite)ENSG00000136997
    Other databases
    Probes
    Probec-MYC (8q24) in normal cells (Bari)
    Litterature
    PubMed499 Pubmed reference(s) in Entrez
    CoreMineMYC
    iHOPMYC
    OncoSearchMYC

    Bibliography

    c-myc and immunoglobulin kappa light chain constant genes are on the 8q+ chromosome of three Burkitt lymphoma lines with t(2;8) translocations.
    Rappold GA, Hameister H, Cremer T, Adolph S, Henglein B, Freese UK, Lenoire GM, Bornkamm GW
    The EMBO journal. 1984 ; 3 (12) : 2951-2955.
    PMID 6441706
     
    Amplification of the c-myc oncogene in a subpopulation of human small cell lung cancer.
    Saksela K, Bergh J, Lehto VP, Nilsson K, Alitalo K
    Cancer research. 1985 ; 45 (4) : 1823-1827.
    PMID 2983887
     
    Myc family genes: a dispersed multi-gene family.
    Depinho RA, Hatton K, Ferrier P, Zimmerman K, Legouy E, Tesfaye A, Collum R, Yancopoulos G, Nisen P, Alt F
    Annals of clinical research. 1986 ; 18 (5-6) : 284-289.
    PMID 3551773
     
    c-myc protooncogene polypeptide expression in endometriosis.
    Schenken RS, Johnson JV, Riehl RM
    American journal of obstetrics and gynecology. 1991 ; 164 (4) : 1031-1036.
    PMID 1707594
     
    The c-myc oncogene in tumor progression.
    Garte SJ
    Critical reviews in oncogenesis. 1993 ; 4 (4) : 435-449.
    PMID 8353142
     
    Chromosomal translocations deregulating c-myc are associated with normal immune responses.
    Roschke V, Kopantzev E, Dertzbaugh M, Rudikoff S
    Oncogene. 1997 ; 14 (25) : 3011-3016.
    PMID 9223664
     
    Repression by the Mad(Mxi1)-Sin3 complex.
    Schreiber-Agus N, DePinho RA
    BioEssays : news and reviews in molecular, cellular and developmental biology. 1998 ; 20 (10) : 808-818.
    PMID 9819568
     
    Amplification of the c-myc oncogene in non-small cell lung cancer.
    Ozkara HA, Ozkara S, Topł▀u S, Criss WE
    Tumori. 1999 ; 85 (6) : 508-511.
    PMID 10774575
     
    MYC oncogenes and human neoplastic disease.
    Nesbit CE, Tersak JM, Prochownik EV
    Oncogene. 1999 ; 18 (19) : 3004-3016.
    PMID 10378696
     
    Proliferation, C-myc, and cyclin D1 expression in diffuse alveolar damage: potential roles in pathogenesis and implications for prognosis.
    Adamson A, Perkins S, Brambilla E, Tripp S, Holden J, Travis W, Guinee D Jr
    Human pathology. 1999 ; 30 (9) : 1050-1057.
    PMID 10492039
     
    REVIEW articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed

    Search in all EBI   NCBI

    Contributor(s)

    Written08-2000Niels B Atkin

    Citation

    This paper should be referenced as such :
    Atkin, NB
    MYC (v-myc myelocytomatosis viral oncogene homolog (avian))
    Atlas Genet Cytogenet Oncol Haematol. 2000;4(4):181-182.
    Free online version   Free pdf version   [Bibliographic record ]
    URL : http://AtlasGeneticsOncology.org/Genes/MYCID27.html

    © Atlas of Genetics and Cytogenetics in Oncology and Haematology
    indexed on : Sat Oct 4 13:06:11 CEST 2014

    Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

    For comments and suggestions or contributions, please contact us

    jlhuret@AtlasGeneticsOncology.org.