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Gene Review

MYC  -  v-myc avian myelocytomatosis viral...

Homo sapiens

Synonyms: BHLHE39, Class E basic helix-loop-helix protein 39, MRTL, MYCC, Myc proto-oncogene protein, ...
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Disease relevance of MYC


Psychiatry related information on MYC

  • NF-kappaB/rel proteins, tumor suppressor p53, and oncogene c-Myc are critical transcription factors involved in coordinating cellular decision-making events in response to external stimuli [7].
  • This analysis provided evidence for the existence of negative and positive Ets regulatory site and suggested a complex interplay between Ets/Id family members and c-Myc that may be an important determinant of the diversity of telomerase activity in leukemia and other cancers [8].

High impact information on MYC


Chemical compound and disease context of MYC


Biological context of MYC


Anatomical context of MYC

  • The present studies demonstrate that BCR ligation of WEHI 231 as well as of normal immature B cells greatly increased expression of CTCF in association with down-regulation of MYC followed by growth arrest and cell death [20].
  • We used an inducible form of the MYC protein to stimulate normal human and rodent fibroblasts [21].
  • We found a large number of binding sites for all three factors; extrapolation suggests there may be approximately 20,000-30,000 E2F1- and MYC-binding sites and approximately 12,000-17,000 active promoters in HeLa cells [22].
  • Copy number analysis of selected genes from these chromosome arms by fluorescence in situ hybridization showed amplification of the MYC oncogene in 54% of the cell lines, whereas CCND1 was amplified in 28% [23].
  • In previous studies, an interactive transcript abundance index (ITAI) comprising three cell cycle control genes, [MYC x E2F1]/p21 accurately distinguished normal from malignant bronchial epithelial cells (BEC), using a cut-off threshold of 7,000 [24].

Associations of MYC with chemical compounds


Physical interactions of MYC

  • A search for INI1-interacting proteins using the two-hybrid system led to the isolation of c-MYC, a transactivator [10].
  • Protein-protein interaction studies indicate that PRMT5 and mSin3A interact with the same hSWI/SNF subunits as those targeted by c-Myc [25].
  • Regulation of MYC promoter activity critically depends on the presence of a binding site for transcription factor E2F [30].
  • We demonstrate, both in vitro by yeast two-hybrid and GST-fusion pull-down experiments, as well as in vivo by coimmunoprecipitation from human tumour cell extracts, that MLH1 interacts with the c-MYC protein [31].
  • Eventually, a single copy of the exogenous hTERT gene was observed in the relatively later passage T-HME cells in which telomere length was elongated and stabilized without obvious activation of endogenous hTERT and c-Myc expression [32].
  • USP28 binds to MYC through an interaction with FBW7alpha, an F-box protein that is part of an SCF-type ubiquitin ligase [33].

Enzymatic interactions of MYC

  • Interestingly, ASK1-signaling attenuated the degradation of ubiquitinated c-Myc without affecting the ubiquitination process [34].
  • MYC recruits PIM1 to the E boxes of the MYC-target genes FOSL1 (FRA-1) and ID2, and PIM1 phosphorylates serine 10 of histone H3 (H3S10) on the nucleosome at the MYC-binding sites, contributing to their transcriptional activation [35].

Regulatory relationships of MYC

  • Our results show that Ser727/Tyr701-phosphorylated Stat1 plays a key role as a prerequisite for the ATRA-induced down-regulation of c-Myc; cyclins A, B, D2, D3, and E; and the simultaneous up-regulation of p27Kip1, associated with arrest in the G0/G1 phase of the cell cycle [36].
  • c-Myc directly regulates the transcription of the NBS1 gene involved in DNA double-strand break repair [37].
  • The nucleophosmin-anaplastic lymphoma kinase fusion protein induces c-Myc expression in pediatric anaplastic large cell lymphomas [26].
  • Restoration of c-Myc in non-adherent cells induces the expression of E2F-1, and hyperphosphorylation of pRb in response to EGF treatment [38].
  • Overexpression of c-Myc inhibits p21WAF1/CIP1 expression and induces S-phase entry in 12-O-tetradecanoylphorbol-13-acetate (TPA)-sensitive human cancer cells [39].
  • LANA (L1006P) retained the ability to bind to c-Myc and activate ERK1, indicating that these events did not require LANA interaction with GSK-3 [40].
  • We report that c-Myc expression in human mammary epithelial cells induces a dramatic change in cell morphology, with some characteristics of an 'epithelial to mesenchymal transition'. E-cadherin expression is repressed by a post-transcriptional mechanism in cells expressing c-Myc [41].

Other interactions of MYC

  • The c-Myc and E2F transcription factors are among the most potent regulators of cell cycle progression in higher eukaryotes [12].
  • The c-MYC-INI1 interaction was observed both in vitro and in vivo [10].
  • We found that constitutive expression of MYC or activation of conditional MycER chimeras led to higher levels of cyclin A and cyclin E mRNA [19].
  • Time courses demonstrated that 4D5 treatment redirects p27(Kip1) onto Cdk2 complexes, an event preceding increased p27(Kip1) expression; this correlates with the downregulation of c-Myc and D-type cyclins (proteins involved in p27(Kip1) sequestration) and the loss of p27(Kip1) from Cdk4 complexes [42].
  • BAF53 forms distinct nuclear complexes and functions as a critical c-Myc-interacting nuclear cofactor for oncogenic transformation [43].

Analytical, diagnostic and therapeutic context of MYC


  1. Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster. Dews, M., Homayouni, A., Yu, D., Murphy, D., Sevignani, C., Wentzel, E., Furth, E.E., Lee, W.M., Enders, G.H., Mendell, J.T., Thomas-Tikhonenko, A. Nat. Genet. (2006) [Pubmed]
  2. Survey of gene amplifications during prostate cancer progression by high-throughout fluorescence in situ hybridization on tissue microarrays. Bubendorf, L., Kononen, J., Koivisto, P., Schraml, P., Moch, H., Gasser, T.C., Willi, N., Mihatsch, M.J., Sauter, G., Kallioniemi, O.P. Cancer Res. (1999) [Pubmed]
  3. Molecular pathogenesis and a consequent classification of multiple myeloma. Bergsagel, P.L., Kuehl, W.M. J. Clin. Oncol. (2005) [Pubmed]
  4. Combined microarray analysis of small cell lung cancer reveals altered apoptotic balance and distinct expression signatures of MYC family gene amplification. Kim, Y.H., Girard, L., Giacomini, C.P., Wang, P., Hernandez-Boussard, T., Tibshirani, R., Minna, J.D., Pollack, J.R. Oncogene (2006) [Pubmed]
  5. Amplification of IGH/MYC fusion in clinically aggressive IGH/BCL2-positive germinal center B-cell lymphomas. Martín-Subero, J.I., Odero, M.D., Hernandez, R., Cigudosa, J.C., Agirre, X., Saez, B., Sanz-García, E., Ardanaz, M.T., Novo, F.J., Gascoyne, R.D., Calasanz, M.J., Siebert, R. Genes Chromosomes Cancer (2005) [Pubmed]
  6. Relative copy number gain of MYC in diagnostic needle biopsies is an independent prognostic factor for prostate cancer patients. Ribeiro, F.R., Henrique, R., Martins, A.T., Jerónimo, C., Teixeira, M.R. Eur. Urol. (2007) [Pubmed]
  7. Synergistic and opposing regulation of the stress-responsive gene IEX-1 by p53, c-Myc, and multiple NF-kappaB/rel complexes. Huang, Y.H., Wu, J.Y., Zhang, Y., Wu, M.X. Oncogene (2002) [Pubmed]
  8. Role of Ets/Id proteins for telomerase regulation in human cancer cells. Xiao, X., Athanasiou, M., Sidorov, I.A., Horikawa, I., Cremona, G., Blair, D., Barret, J.C., Dimitrov, D.S. Exp. Mol. Pathol. (2003) [Pubmed]
  9. Replication from oriP of Epstein-Barr virus requires human ORC and is inhibited by geminin. Dhar, S.K., Yoshida, K., Machida, Y., Khaira, P., Chaudhuri, B., Wohlschlegel, J.A., Leffak, M., Yates, J., Dutta, A. Cell (2001) [Pubmed]
  10. c-MYC interacts with INI1/hSNF5 and requires the SWI/SNF complex for transactivation function. Cheng, S.W., Davies, K.P., Yung, E., Beltran, R.J., Yu, J., Kalpana, G.V. Nat. Genet. (1999) [Pubmed]
  11. Direct activation of TERT transcription by c-MYC. Wu, K.J., Grandori, C., Amacker, M., Simon-Vermot, N., Polack, A., Lingner, J., Dalla-Favera, R. Nat. Genet. (1999) [Pubmed]
  12. The novel ATM-related protein TRRAP is an essential cofactor for the c-Myc and E2F oncoproteins. McMahon, S.B., Van Buskirk, H.A., Dugan, K.A., Copeland, T.D., Cole, M.D. Cell (1998) [Pubmed]
  13. c-Myc or cyclin D1 mimics estrogen effects on cyclin E-Cdk2 activation and cell cycle reentry. Prall, O.W., Rogan, E.M., Musgrove, E.A., Watts, C.K., Sutherland, R.L. Mol. Cell. Biol. (1998) [Pubmed]
  14. Molecular mechanism of cell cycle blockage of hepatoma SK-Hep-1 cells by Epimedin C through suppression of mitogen-activated protein kinase activation and increased expression of CDK inhibitors p21(Cip1) and p27(Kip1). Liu, T.Z., Chen, C.Y., Yiin, S.J., Chen, C.H., Cheng, J.T., Shih, M.K., Wang, Y.S., Chern, C.L. Food Chem. Toxicol. (2006) [Pubmed]
  15. Ketogenic HMGCS2 Is a c-Myc Target Gene Expressed in Differentiated Cells of Human Colonic Epithelium and Down-Regulated in Colon Cancer. Camarero, N., Mascaró, C., Mayordomo, C., Vilardell, F., Haro, D., Marrero, P.F. Mol. Cancer Res. (2006) [Pubmed]
  16. Nontumorigenic squamous cell carcinoma line converted to tumorigenicity with methyl methanesulfonate without activation of HRAS or MYC. Milo, G.E., Shuler, C., Kurian, P., French, B.T., Mannix, D.G., Noyes, I., Hollering, J., Sital, N., Schuller, D., Trewyn, R.W. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  17. Resveratrol induces apoptosis in transformed follicular lymphoma OCI-LY8 cells: Evidence for a novel mechanism involving inhibition of BCL6 signaling. Faber, A.C., Chiles, T.C. Int. J. Oncol. (2006) [Pubmed]
  18. Werner syndrome protein limits MYC-induced cellular senescence. Grandori, C., Wu, K.J., Fernandez, P., Ngouenet, C., Grim, J., Clurman, B.E., Moser, M.J., Oshima, J., Russell, D.W., Swisshelm, K., Frank, S., Amati, B., Dalla-Favera, R., Monnat, R.J. Genes Dev. (2003) [Pubmed]
  19. Differential modulation of cyclin gene expression by MYC. Jansen-Dürr, P., Meichle, A., Steiner, P., Pagano, M., Finke, K., Botz, J., Wessbecher, J., Draetta, G., Eilers, M. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  20. CTCF functions as a critical regulator of cell-cycle arrest and death after ligation of the B cell receptor on immature B cells. Qi, C.F., Martensson, A., Mattioli, M., Dalla-Favera, R., Lobanenkov, V.V., Morse, H.C. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  21. Overexpression of MYC causes p53-dependent G2 arrest of normal fibroblasts. Felsher, D.W., Zetterberg, A., Zhu, J., Tlsty, T., Bishop, J.M. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  22. Unbiased location analysis of E2F1-binding sites suggests a widespread role for E2F1 in the human genome. Bieda, M., Xu, X., Singer, M.A., Green, R., Farnham, P.J. Genome Res. (2006) [Pubmed]
  23. Frequent amplification of 8q24, 11q, 17q, and 20q-specific genes in pancreatic cancer. Mahlamäki, E.H., Bärlund, M., Tanner, M., Gorunova, L., Höglund, M., Karhu, R., Kallioniemi, A. Genes Chromosomes Cancer (2002) [Pubmed]
  24. Stable low-level expression of p21WAF1/CIP1 in A549 human bronchogenic carcinoma cell line-derived clones down-regulates E2F1 mRNA and restores cell proliferation control. Graves, T.G., Harr, M.W., Crawford, E.L., Willey, J.C. Mol. Cancer (2006) [Pubmed]
  25. mSin3A/histone deacetylase 2- and PRMT5-containing Brg1 complex is involved in transcriptional repression of the Myc target gene cad. Pal, S., Yun, R., Datta, A., Lacomis, L., Erdjument-Bromage, H., Kumar, J., Tempst, P., Sif, S. Mol. Cell. Biol. (2003) [Pubmed]
  26. The nucleophosmin-anaplastic lymphoma kinase fusion protein induces c-Myc expression in pediatric anaplastic large cell lymphomas. Raetz, E.A., Perkins, S.L., Carlson, M.A., Schooler, K.P., Carroll, W.L., Virshup, D.M. Am. J. Pathol. (2002) [Pubmed]
  27. Beta-catenin-mediated transactivation and cell-cell adhesion pathways are important in curcumin (diferuylmethane)-induced growth arrest and apoptosis in colon cancer cells. Jaiswal, A.S., Marlow, B.P., Gupta, N., Narayan, S. Oncogene (2002) [Pubmed]
  28. Six lysine residues on c-Myc are direct substrates for acetylation by p300. Zhang, K., Faiola, F., Martinez, E. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  29. Inhibition of HMGcoA reductase by atorvastatin prevents and reverses MYC-induced lymphomagenesis. Shachaf, C.M., Perez, O.D., Youssef, S., Fan, A.C., Elchuri, S., Goldstein, M.J., Shirer, A.E., Sharpe, O., Chen, J., Mitchell, D.J., Chang, M., Nolan, G.P., Steinman, L., Felsher, D.W. Blood (2007) [Pubmed]
  30. E2F-dependent regulation of human MYC: trans-activation by cyclins D1 and A overrides tumour suppressor protein functions. Oswald, F., Lovec, H., Möröy, T., Lipp, M. Oncogene (1994) [Pubmed]
  31. Interactions of the DNA mismatch repair proteins MLH1 and MSH2 with c-MYC and MAX. Mac Partlin, M., Homer, E., Robinson, H., McCormick, C.J., Crouch, D.H., Durant, S.T., Matheson, E.C., Hall, A.G., Gillespie, D.A., Brown, R. Oncogene (2003) [Pubmed]
  32. Events in the immortalizing process of primary human mammary epithelial cells by the catalytic subunit of human telomerase. Kim, H., Farris, J., Christman, S.A., Kong, B.W., Foster, L.K., O'Grady, S.M., Foster, D.N. Biochem. J. (2002) [Pubmed]
  33. The ubiquitin-specific protease USP28 is required for MYC stability. Popov, N., Wanzel, M., Madiredjo, M., Zhang, D., Beijersbergen, R., Bernards, R., Moll, R., Elledge, S.J., Eilers, M. Nat. Cell Biol. (2007) [Pubmed]
  34. ASK1-signaling promotes c-Myc protein stability during apoptosis. Noguchi, K., Kokubu, A., Kitanaka, C., Ichijo, H., Kuchino, Y. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  35. PIM1-dependent phosphorylation of histone H3 at serine 10 is required for MYC-dependent transcriptional activation and oncogenic transformation. Zippo, A., De Robertis, A., Serafini, R., Oliviero, S. Nat. Cell Biol. (2007) [Pubmed]
  36. Ser727/Tyr701-phosphorylated Stat1 is required for the regulation of c-Myc, cyclins, and p27Kip1 associated with ATRA-induced G0/G1 arrest of U-937 cells. Dimberg, A., Karlberg, I., Nilsson, K., Oberg, F. Blood (2003) [Pubmed]
  37. c-Myc directly regulates the transcription of the NBS1 gene involved in DNA double-strand break repair. Chiang, Y.C., Teng, S.C., Su, Y.N., Hsieh, F.J., Wu, K.J. J. Biol. Chem. (2003) [Pubmed]
  38. Adhesion-regulated G1 cell cycle arrest in epithelial cells requires the downregulation of c-Myc. Benaud, C.M., Dickson, R.B. Oncogene (2001) [Pubmed]
  39. Overexpression of c-Myc inhibits p21WAF1/CIP1 expression and induces S-phase entry in 12-O-tetradecanoylphorbol-13-acetate (TPA)-sensitive human cancer cells. Mitchell, K.O., El-Deiry, W.S. Cell Growth Differ. (1999) [Pubmed]
  40. The Kaposi's sarcoma-associated herpesvirus LANA protein stabilizes and activates c-Myc. Liu, J., Martin, H.J., Liao, G., Hayward, S.D. J. Virol. (2007) [Pubmed]
  41. E-cadherin repression contributes to c-Myc-induced epithelial cell transformation. Cowling, V.H., Cole, M.D. Oncogene (2007) [Pubmed]
  42. ErbB2 potentiates breast tumor proliferation through modulation of p27(Kip1)-Cdk2 complex formation: receptor overexpression does not determine growth dependency. Lane, H.A., Beuvink, I., Motoyama, A.B., Daly, J.M., Neve, R.M., Hynes, N.E. Mol. Cell. Biol. (2000) [Pubmed]
  43. BAF53 forms distinct nuclear complexes and functions as a critical c-Myc-interacting nuclear cofactor for oncogenic transformation. Park, J., Wood, M.A., Cole, M.D. Mol. Cell. Biol. (2002) [Pubmed]
  44. Presence of three recurrent chromosomal reaarrangements, t(2;3)(p12;q37), del(8)(q24), and t(14;18), in an acute lymphoblastic leukemia. Berger, R., Flexor, M., Le Coniat, M., Larsen, C.J. Cancer Genet. Cytogenet. (1996) [Pubmed]
  45. Monoamine oxidase A and repressor R1 are involved in apoptotic signaling pathway. Ou, X.M., Chen, K., Shih, J.C. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  46. A strategy for identifying transcription factor binding sites reveals two classes of genomic c-Myc target sites. Haggerty, T.J., Zeller, K.I., Osthus, R.C., Wonsey, D.R., Dang, C.V. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  47. Elevated protein expression of cyclin D1 and Fra-1 but decreased expression of c-Myc in human colorectal adenocarcinomas overexpressing beta-catenin. Wang, H.L., Wang, J., Xiao, S.Y., Haydon, R., Stoiber, D., He, T.C., Bissonnette, M., Hart, J. Int. J. Cancer (2002) [Pubmed]
  48. Molecular analysis of oncogenes, ras family genes (N-ras, K-ras, H-ras), myc family genes (c-myc, N-myc) and mdm2 in natural killer cell neoplasms. Sugimoto, K.J., Kawamata, N., Sakajiri, S., Oshimi, K. Jpn. J. Cancer Res. (2002) [Pubmed]
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