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Gene Review

MYCN  -  v-myc avian myelocytomatosis viral...

Homo sapiens

Synonyms: BHLHE37, Class E basic helix-loop-helix protein 37, MODED, MYCNOT, N-myc, ...
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Disease relevance of MYCN


Psychiatry related information on MYCN


High impact information on MYCN

  • All mutations are predicted to disrupt both the full-length protein and a new shortened MYCN isoform, suggesting that multiple aspects of early embryogenesis and postnatal brain growth in humans are tightly regulated by MYCN dosage [9].
  • This gain has been associated with advanced disease, patients who are > or =1 year old, deletion of chromosome arm 1p, and amplification of the N-myc oncogene, all of which predict an adverse outcome [10].
  • Clinical and survival information were collected, along with data on 1p, N-myc, and ploidy [10].
  • The findings suggest that expression of this multidrug-resistance gene accounts for the association between N-myc amplification and reduced survival [11].
  • The expression of MRP by neuroblastoma cells correlates with N-myc oncogene amplification, a well-established prognostic indicator in patients with neuroblastoma [11].

Chemical compound and disease context of MYCN


Biological context of MYCN


Anatomical context of MYCN

  • Furthermore, the MYCN gene is also present in multiple copies in these two cell lines, suggesting coamplification of the two genes [18].
  • These data suggest that inappropriate perinatal MycN expression in paravertebral ganglia cells from TH-MYCN mice initiated tumorigenesis by altering the physiologic process of neural crest cell deletion [2].
  • Paravertebral neuronal cells cultured from perinatal TH-MYCN mice exhibited 3- to 10-fold resistance to nerve growth factor (NGF) withdrawal, compared with normal mice [2].
  • Finally, we show a significant correlation between centrosome amplification and MYCN amplification in primary neuroblastoma tumors [19].
  • Caspase-9 and Apaf-1 are expressed and functionally active in human neuroblastoma tumor cell lines with 1p36 LOH and amplified MYCN [20].

Associations of MYCN with chemical compounds

  • In addition, MYCN constitutive expression abolishes HMGA1 repression by RA [21].
  • In addition, we provide evidence that E2F proteins are involved in the negative regulation of MYCN by TGF-beta and retinoic acid [22].
  • Therefore, we analysed the mechanism of action of DFMO and/or SAM486A in two established MYCN-amplified human NB cell lines [23].
  • A nutlin-3 response was observed regardless of MYCN amplification status [24].
  • In Tet21N cells, which conditionally express MYCN, greatly enhanced (nearly 6-fold) sensitivity to WP744 killing was seen when this oncogene was induced, while enhanced sensitivity to Dox was more modest (2-fold) under MYCN-induced conditions [25].

Physical interactions of MYCN

  • Expression of a MYCN-interacting isoform of the tumor suppressor BIN1 is reduced in neuroblastomas with unfavorable biological features [26].
  • Finally, DNA cross-linking experiments show that nestin binds DNA in N-myc-amplified N-type cell lines [27].
  • However, the ability of the CD44 receptor to bind immobilized hyaluronan was restricted to CD44H+ cell lines without NMYC amplification (SH-EP and ACN) [28].
  • The high-mobility group transcription factor Sox10 interacts with the N-myc-interacting protein Nmi [29].
  • The alteration in the N-myc level was well correlated with the formation of complexes with the E2F motif in the N-myc promoter region, and no complex was formed with cell extracts prepared from cells treated with HMBA for 12-24 h [30].

Enzymatic interactions of MYCN

  • These results suggest that two serine residues of the acidic central region of the N-myc protein are phosphorylated by CKII in vivo as well as in vitro [31].

Regulatory relationships of MYCN


Other interactions of MYCN

  • Coamplification of DDX1 correlates with an improved survival probability in children with MYCN-amplified human neuroblastoma [17].
  • These data support the hypothesis that elevated MDM2 levels contribute to MYCN-induced genomic instability through altered regulation of centrosome replication in neuroblastoma [19].
  • Either 5' or 3' deletion variants of the 1,600 bp promoter/luciferase reporter strongly decreased luciferase activity, suggesting that, more than a single site, the cooperative function of multiple cis-acting elements mediates direct HMGA1 transactivation by MYCN [21].
  • Additionally, overexpression of the proto-oncogenes CCND2 and MYCN were confirmed from the literature [35].
  • Using an MDR1 promoter-CAT construct, we have shown that the MycN protein activates MDR1 transcription both in exogenous transient MYCN-transfected SK-N-SH cells and in endogenous BM metastatic neuroblasts with an increase in the MYCN transcript level [36].

Analytical, diagnostic and therapeutic context of MYCN


  1. Natural killer T cells infiltrate neuroblastomas expressing the chemokine CCL2. Metelitsa, L.S., Wu, H.W., Wang, H., Yang, Y., Warsi, Z., Asgharzadeh, S., Groshen, S., Wilson, S.B., Seeger, R.C. J. Exp. Med. (2004) [Pubmed]
  2. Mechanisms of embryonal tumor initiation: distinct roles for MycN expression and MYCN amplification. Hansford, L.M., Thomas, W.D., Keating, J.M., Burkhart, C.A., Peaston, A.E., Norris, M.D., Haber, M., Armati, P.J., Weiss, W.A., Marshall, G.M. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  3. Co-amplification of MYCN and a DEAD box gene (DDX1) in primary neuroblastoma. Squire, J.A., Thorner, P.S., Weitzman, S., Maggi, J.D., Dirks, P., Doyle, J., Hale, M., Godbout, R. Oncogene (1995) [Pubmed]
  4. Mapping of chromosomal imbalances in gastric adenocarcinoma revealed amplified protooncogenes MYCN, MET, WNT2, and ERBB2. Nessling, M., Solinas-Toldo, S., Wilgenbus, K.K., Borchard, F., Lichter, P. Genes Chromosomes Cancer (1998) [Pubmed]
  5. Oncogene MYCN regulates localization of NKT cells to the site of disease in neuroblastoma. Song, L., Ara, T., Wu, H.W., Woo, C.W., Reynolds, C.P., Seeger, R.C., DeClerck, Y.A., Thiele, C.J., Sposto, R., Metelitsa, L.S. J. Clin. Invest. (2007) [Pubmed]
  6. Genes proximal and distal to MYCN are highly expressed in human neuroblastoma as visualized by comparative expressed sequence hybridization. Stock, C., Bozsaky, E., Watzinger, F., Poetschger, U., Orel, L., Lion, T., Kowalska, A., Ambros, P.F. Am. J. Pathol. (2008) [Pubmed]
  7. Quantification of MYCN, DDX1, and NAG gene copy number in neuroblastoma using a real-time quantitative PCR assay. De Preter, K., Speleman, F., Combaret, V., Lunec, J., Laureys, G., Eussen, B.H., Francotte, N., Board, J., Pearson, A.D., De Paepe, A., Van Roy, N., Vandesompele, J. Mod. Pathol. (2002) [Pubmed]
  8. Cell death signaling in the cerebellum in Creutzfeldt-Jakob disease. Puig, B., Ferrer, I. Acta Neuropathol. (2001) [Pubmed]
  9. MYCN haploinsufficiency is associated with reduced brain size and intestinal atresias in Feingold syndrome. van Bokhoven, H., Celli, J., van Reeuwijk, J., Rinne, T., Glaudemans, B., van Beusekom, E., Rieu, P., Newbury-Ecob, R.A., Chiang, C., Brunner, H.G. Nat. Genet. (2005) [Pubmed]
  10. Gain of chromosome arm 17q and adverse outcome in patients with neuroblastoma. Bown, N., Cotterill, S., Lastowska, M., O'Neill, S., Pearson, A.D., Plantaz, D., Meddeb, M., Danglot, G., Brinkschmidt, C., Christiansen, H., Laureys, G., Speleman, F., Nicholson, J., Bernheim, A., Betts, D.R., Vandesompele, J., Van Roy, N. N. Engl. J. Med. (1999) [Pubmed]
  11. Expression of the gene for multidrug-resistance-associated protein and outcome in patients with neuroblastoma. Norris, M.D., Bordow, S.B., Marshall, G.M., Haber, P.S., Cohn, S.L., Haber, M. N. Engl. J. Med. (1996) [Pubmed]
  12. E2F and Sp1/Sp3 Synergize but are not sufficient to activate the MYCN gene in neuroblastomas. Kramps, C., Strieder, V., Sapetschnig, A., Suske, G., Lutz, W. J. Biol. Chem. (2004) [Pubmed]
  13. Expression of trkB in human neuroblastoma in relation to MYCN expression and retinoic acid treatment. Edsjö, A., Lavenius, E., Nilsson, H., Hoehner, J.C., Simonsson, P., Culp, L.A., Martinsson, T., Larsson, C., Påhlman, S. Lab. Invest. (2003) [Pubmed]
  14. The MYCN protein of human neuroblastoma cells is phosphorylated by casein kinase II in the central region and at serine 367. Hamann, U., Wenzel, A., Frank, R., Schwab, M. Oncogene (1991) [Pubmed]
  15. Induction of senescence in MYCN amplified neuroblastoma cell lines by hydroxyurea. Narath, R., Ambros, I.M., Kowalska, A., Bozsaky, E., Boukamp, P., Ambros, P.F. Genes Chromosomes Cancer (2007) [Pubmed]
  16. The p53 regulatory gene MDM2 is a direct transcriptional target of MYCN in neuroblastoma. Slack, A., Chen, Z., Tonelli, R., Pule, M., Hunt, L., Pession, A., Shohet, J.M. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  17. Coamplification of DDX1 correlates with an improved survival probability in children with MYCN-amplified human neuroblastoma. Weber, A., Imisch, P., Bergmann, E., Christiansen, H. J. Clin. Oncol. (2004) [Pubmed]
  18. Amplification of a DEAD box protein gene in retinoblastoma cell lines. Godbout, R., Squire, J. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  19. MYCN-directed centrosome amplification requires MDM2-mediated suppression of p53 activity in neuroblastoma cells. Slack, A.D., Chen, Z., Ludwig, A.D., Hicks, J., Shohet, J.M. Cancer Res. (2007) [Pubmed]
  20. Caspase-9 and Apaf-1 are expressed and functionally active in human neuroblastoma tumor cell lines with 1p36 LOH and amplified MYCN. Teitz, T., Wei, T., Liu, D., Valentine, V., Valentine, M., Grenet, J., Lahti, J.M., Kidd, V.J. Oncogene (2002) [Pubmed]
  21. High mobility group A1 is a molecular target for MYCN in human neuroblastoma. Giannini, G., Cerignoli, F., Mellone, M., Massimi, I., Ambrosi, C., Rinaldi, C., Dominici, C., Frati, L., Screpanti, I., Gulino, A. Cancer Res. (2005) [Pubmed]
  22. E2F proteins regulate MYCN expression in neuroblastomas. Strieder, V., Lutz, W. J. Biol. Chem. (2003) [Pubmed]
  23. Key role for p27Kip1, retinoblastoma protein Rb, and MYCN in polyamine inhibitor-induced G1 cell cycle arrest in MYCN-amplified human neuroblastoma cells. Wallick, C.J., Gamper, I., Thorne, M., Feith, D.J., Takasaki, K.Y., Wilson, S.M., Seki, J.A., Pegg, A.E., Byus, C.V., Bachmann, A.S. Oncogene (2005) [Pubmed]
  24. Small-Molecule MDM2 Antagonists as a New Therapy Concept for Neuroblastoma. Van Maerken, T., Speleman, F., Vermeulen, J., Lambertz, I., De Clercq, S., De Smet, E., Yigit, N., Coppens, V., Philipp??, J., De Paepe, A., Marine, J.C., Vandesompele, J. Cancer Res. (2006) [Pubmed]
  25. WP744 is a novel anthracycline with enhanced activity against neuroblastoma. Inge, T.H., Harris, N.L., Wu, J., Azizkhan, R.G., Priebe, W. J. Surg. Res. (2004) [Pubmed]
  26. Expression of a MYCN-interacting isoform of the tumor suppressor BIN1 is reduced in neuroblastomas with unfavorable biological features. Tajiri, T., Liu, X., Thompson, P.M., Tanaka, S., Suita, S., Zhao, H., Maris, J.M., Prendergast, G.C., Hogarty, M.D. Clin. Cancer Res. (2003) [Pubmed]
  27. Nestin is a potential mediator of malignancy in human neuroblastoma cells. Thomas, S.K., Messam, C.A., Spengler, B.A., Biedler, J.L., Ross, R.A. J. Biol. Chem. (2004) [Pubmed]
  28. Absence of functional CD44 hyaluronan receptor on human NMYC-amplified neuroblastoma cells. Gross, N., Balmas, K., Brognara, C.B. Cancer Res. (1997) [Pubmed]
  29. The high-mobility group transcription factor Sox10 interacts with the N-myc-interacting protein Nmi. Schlierf, B., Lang, S., Kosian, T., Werner, T., Wegner, M. J. Mol. Biol. (2005) [Pubmed]
  30. Protein phosphorylation required for the formation of E2F complexes regulates N-myc transcription during differentiation of human embryonal carcinoma cells. Hara, E., Okamoto, S., Nakada, S., Taya, Y., Sekiya, S., Oda, K. Oncogene (1993) [Pubmed]
  31. Specific phosphorylation of the acidic central region of the N-myc protein by casein kinase II. Hagiwara, T., Nakaya, K., Nakamura, Y., Nakajima, H., Nishimura, S., Taya, Y. Eur. J. Biochem. (1992) [Pubmed]
  32. MDM2 as a critical effector of the MYCN oncogene in tumorigenesis. Slack, A., Shohet, J.M. Cell Cycle (2005) [Pubmed]
  33. MYCN-mediated regulation of the MRP1 promoter in human neuroblastoma. Manohar, C.F., Bray, J.A., Salwen, H.R., Madafiglio, J., Cheng, A., Flemming, C., Marshall, G.M., Norris, M.D., Haber, M., Cohn, S.L. Oncogene (2004) [Pubmed]
  34. BIN1 inhibits colony formation and induces apoptosis in neuroblastoma cell lines with MYCN amplification. Hogarty, M.D., Liu, X., Thompson, P.M., White, P.S., Sulman, E.P., Maris, J.M., Brodeur, G.M. Med. Pediatr. Oncol. (2000) [Pubmed]
  35. New insights into testicular germ cell tumorigenesis from gene expression profiling. Skotheim, R.I., Monni, O., Mousses, S., Fosså, S.D., Kallioniemi, O.P., Lothe, R.A., Kallioniemi, A. Cancer Res. (2002) [Pubmed]
  36. MYCN enhances P-gp/MDR1 gene expression in the human metastatic neuroblastoma IGR-N-91 model. Blanc, E., Goldschneider, D., Ferrandis, E., Barrois, M., Le Roux, G., Leonce, S., Douc-Rasy, S., Bénard, J., Raguénez, G. Am. J. Pathol. (2003) [Pubmed]
  37. Genome-wide array CGH analysis of murine neuroblastoma reveals distinct genomic aberrations which parallel those in human tumors. Hackett, C.S., Hodgson, J.G., Law, M.E., Fridlyand, J., Osoegawa, K., de Jong, P.J., Nowak, N.J., Pinkel, D., Albertson, D.G., Jain, A., Jenkins, R., Gray, J.W., Weiss, W.A. Cancer Res. (2003) [Pubmed]
  38. ID2 expression is not associated with MYCN amplification or expression in human neuroblastomas. Wang, Q., Hii, G., Shusterman, S., Mosse, Y., Winter, C.L., Guo, C., Zhao, H., Rappaport, E., Hogarty, M.D., Maris, J.M. Cancer Res. (2003) [Pubmed]
  39. Minichromosome maintenance protein MCM7 is a direct target of the MYCN transcription factor in neuroblastoma. Shohet, J.M., Hicks, M.J., Plon, S.E., Burlingame, S.M., Stuart, S., Chen, S.Y., Brenner, M.K., Nuchtern, J.G. Cancer Res. (2002) [Pubmed]
  40. Gene expression profiling in response to the histone deacetylase inhibitor BL1521 in neuroblastoma. de Ruijter, A.J., Meinsma, R.J., Bosma, P., Kemp, S., Caron, H.N., van Kuilenburg, A.B. Exp. Cell Res. (2005) [Pubmed]
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