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Gene Review

Mycn  -  v-myc myelocytomatosis viral related...

Mus musculus

Synonyms: N-myc, N-myc proto-oncogene protein, Nmyc, Nmyc-1, Nmyc1, ...
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Disease relevance of Mycn


Psychiatry related information on Mycn


High impact information on Mycn

  • In all these T cell lymphomas either c-myc or N-myc was activated by proviral insertion, suggesting strong cooperation between pim-1 and myc in lymphomagenesis [7].
  • In neuroblastoma, an embryonal tumour derived from the neural crest, Id2 is overexpressed in cells carrying extra copies of the N-myc gene [8].
  • Activated N-myc and L-myc expression has been implicated in oncogenesis; for example, although N-myc expression has been found in all neuroblastomas tested, activated (greatly increased) N-myc expression, resulting from gene amplification, is correlated with progression of the tumour [9].
  • The L-myc gene is less well characterized, but shows homology to N-myc and c-myc (ref. 6; also see below). c-myc is expressed in most dividing cells, and deregulated expression of this gene has been implicated in the development of many classes of tumours [9].
  • The N-myc and c-myc genes have 5'-noncoding exons, strikingly homologous coding regions, and display similar oncogenic potential in an in vitro transformation assay [9].

Chemical compound and disease context of Mycn

  • An exceptional mouse plasmacytoma with a new kappa/N-myc [T(6; 12) (C1; B)] translocation expresses N-myc but not c-myc [10].
  • Effect of vitamin E succinate and a cAMP-stimulating agent on the expression of c-myc and N-myc and H-ras in murine neuroblastoma cells [11].
  • A nude mouse model for human neuroblastoma has been developed to examine possible relationships between amplification/over-expression of the N-myc oncogene and altered regulation of expression of specific integrin subunits during tumor progression [12].
  • It is shown in this paper that serum growth factors are required for activation of expression of gene encoding translation initiation factor 4E (eIF-4E) in non-transformed NIH 3T3 and Rat-1 fibroblasts but this requirement is lost in C6 glioblastoma, A431 carcinoma and N-myc transformed Rat-1 cells [13].

Biological context of Mycn

  • In particular, we found that in cerebellar granule neuron precursors, the N-myc transcription factor communicates with the cell cycle machinery via cyclins D1 and D2, but not D3, explaining the inability of D3-only mice to up-regulate cyclin D3 in this compartment [14].
  • Targeted deletion of N-myc results in severely compromised proliferation as shown by a striking decrease in S phase and mitotic cells as well as in cells expressing the Myc target gene cyclin D2, whereas apoptosis is unaffected [2].
  • Previously, we have shown that TGF-beta 1 inhibits branching morphogenesis and N-myc expression in mouse embryonic lung cultures [15].
  • For the N-myc and L-myc oncogenes, expression was also highest in prenatal and newborn tissue as compared to the 6-month young adult, but little or no further change was found at older ages [16].
  • Taken together, these results indicate that the expression of the proto-oncogenes c-, L- and N-myc is dependent not only on tissue and embryonic development, as previously shown by other workers, but also on age past the young adult stage of life span [16].

Anatomical context of Mycn

  • N-myc is essential during neurogenesis for the rapid expansion of progenitor cell populations and the inhibition of neuronal differentiation [2].
  • In addition, loss of N-myc disrupts neuronal differentiation as evidenced by ectopic staining of the neuron specific marker betaTUBIII in the cerebrum [2].
  • For example, during mouse lens maturation, the growth arrest and differentiation of epithelial cells into lens fiber cells is associated with a decrease in L- and c-myc expression and a reciprocal rise in N-myc levels [17].
  • Lmyc, but not c-myc and Nmyc, was upregulated in terminally differentiated visceral endoderm cells [18].
  • However, substantial tissue-dependent differences in expression were also found, and no expression at all was detected at any age for N-myc in liver and for L-myc in heart, small intestine and liver [16].

Associations of Mycn with chemical compounds


Physical interactions of Mycn


Regulatory relationships of Mycn

  • We present a model whereby Tbx2 directly represses Nmyc1 in outflow tract and atrioventricular canal of the developing heart, resulting in relatively low proliferation [22].
  • According to this interpretation, constitutive activation of N-myc would suppress the expression of c-myc, but would not interfere with the differentiation of the pro-B cell into a fully mature plasma cell [24].
  • We have generated transgenic mouse lines that carry one of three different constructs in which the murine N-myc gene is expressed under the control of the immunoglobulin heavy chain transcriptional enhancer element (E mu-N-myc genes) [25].
  • Our data present a paradigm by which T-box proteins regulate regional differences in Nmyc1 expression and proliferation to effect organ morphogenesis [22].
  • We report a new common proviral insertion site in murine leukemia virus-induced T cell lymphomas to be N-myc [26].

Other interactions of Mycn


Analytical, diagnostic and therapeutic context of Mycn


  1. Activities of N-Myc in the developing limb link control of skeletal size with digit separation. Ota, S., Zhou, Z.Q., Keene, D.R., Knoepfler, P., Hurlin, P.J. Development (2007) [Pubmed]
  2. N-myc is essential during neurogenesis for the rapid expansion of progenitor cell populations and the inhibition of neuronal differentiation. Knoepfler, P.S., Cheng, P.F., Eisenman, R.N. Genes Dev. (2002) [Pubmed]
  3. Transcriptional profiling of the Sonic hedgehog response: a critical role for N-myc in proliferation of neuronal precursors. Oliver, T.G., Grasfeder, L.L., Carroll, A.L., Kaiser, C., Gillingham, C.L., Lin, S.M., Wickramasinghe, R., Scott, M.P., Wechsler-Reya, R.J. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  4. Id2 is critical for cellular proliferation and is the oncogenic effector of N-myc in human neuroblastoma. Lasorella, A., Boldrini, R., Dominici, C., Donfrancesco, A., Yokota, Y., Inserra, A., Iavarone, A. Cancer Res. (2002) [Pubmed]
  5. Provirus integration at the 3' region of N-myc in cell lines established from thymic lymphomas spontaneously formed in AKR mice and a [(BALB/c x B6)F1----AKR] bone marrow chimera. Yano, Y., Kobayashi, S., Yasumizu, R., Tamaki, J., Kubo, M., Sasaki, A., Hasan, S., Okuyama, H., Inaba, M., Ikehara, S. Jpn. J. Cancer Res. (1991) [Pubmed]
  6. E mu N- and E mu L-myc cooperate with E mu pim-1 to generate lymphoid tumors at high frequency in double-transgenic mice. Möröy, T., Verbeek, S., Ma, A., Achacoso, P., Berns, A., Alt, F. Oncogene (1991) [Pubmed]
  7. Predisposition to lymphomagenesis in pim-1 transgenic mice: cooperation with c-myc and N-myc in murine leukemia virus-induced tumors. van Lohuizen, M., Verbeek, S., Krimpenfort, P., Domen, J., Saris, C., Radaszkiewicz, T., Berns, A. Cell (1989) [Pubmed]
  8. Id2 is a retinoblastoma protein target and mediates signalling by Myc oncoproteins. Lasorella, A., Noseda, M., Beyna, M., Yokota, Y., Iavarone, A. Nature (2000) [Pubmed]
  9. Differential expression of myc family genes during murine development. Zimmerman, K.A., Yancopoulos, G.D., Collum, R.G., Smith, R.K., Kohl, N.E., Denis, K.A., Nau, M.M., Witte, O.N., Toran-Allerand, D., Gee, C.E. Nature (1986) [Pubmed]
  10. An exceptional mouse plasmacytoma with a new kappa/N-myc [T(6; 12) (C1; B)] translocation expresses N-myc but not c-myc. Silva, S., Wang, Y., Babonits, M., Axelson, H., Wiener, F., Klein, G. Curr. Top. Microbiol. Immunol. (1992) [Pubmed]
  11. Effect of vitamin E succinate and a cAMP-stimulating agent on the expression of c-myc and N-myc and H-ras in murine neuroblastoma cells. Cohrs, R.J., Torelli, S., Prasad, K.N., Edwards-Prasad, J., Sharma, O.K. Int. J. Dev. Neurosci. (1991) [Pubmed]
  12. Inverse expressions of the N-myc oncogene and beta 1 integrin in human neuroblastoma: relationships to disease progression in a nude mouse model system. Judware, R., Lechner, R., Culp, L.A. Clin. Exp. Metastasis (1995) [Pubmed]
  13. Growth factor-independent expression of the gene encoding eukaryotic translation initiation factor 4E in transformed cell lines. Rosenwald, I.B. Cancer Lett. (1995) [Pubmed]
  14. Development of mice expressing a single D-type cyclin. Ciemerych, M.A., Kenney, A.M., Sicinska, E., Kalaszczynska, I., Bronson, R.T., Rowitch, D.H., Gardner, H., Sicinski, P. Genes Dev. (2002) [Pubmed]
  15. pRb is necessary for inhibition of N-myc expression by TGF-beta 1 in embryonic lung organ cultures. Serra, R., Moses, H.L. Development (1995) [Pubmed]
  16. Tissue and age specific expression of the myc proto-oncogene family throughout the life span of the C57BL/6J mouse strain. Semsei, I., Ma, S.Y., Cutler, R.G. Oncogene (1989) [Pubmed]
  17. Contrasting roles for c-Myc and L-Myc in the regulation of cellular growth and differentiation in vivo. Morgenbesser, S.D., Schreiber-Agus, N., Bidder, M., Mahon, K.A., Overbeek, P.A., Horner, J., DePinho, R.A. EMBO J. (1995) [Pubmed]
  18. Chromosome localization and expression pattern of Lmyc and Bmyc in murine embryonal carcinoma cells. Ingvarsson, S., Sundaresan, S., Jin, P., Francke, U., Asker, C., Sümegi, J., Klein, G., Sejersen, T. Oncogene (1988) [Pubmed]
  19. Pro-apoptotic activity of N-myc in activation-induced cell death of microglia. Jung, D.Y., Lee, H., Suk, K. J. Neurochem. (2005) [Pubmed]
  20. Embryonic lethality resulting from disruption of both N-myc alleles in mouse zygotes. Sawai, S., Shimono, A., Hanaoka, K., Kondoh, H. New Biol. (1991) [Pubmed]
  21. Rapid and transient decrease of N-myc expression in retinoic acid-induced differentiation of OTF9 teratocarcinoma stem cells. Kato, K., Kanamori, A., Kondoh, H. Mol. Cell. Biol. (1990) [Pubmed]
  22. T-box genes coordinate regional rates of proliferation and regional specification during cardiogenesis. Cai, C.L., Zhou, W., Yang, L., Bu, L., Qyang, Y., Zhang, X., Li, X., Rosenfeld, M.G., Chen, J., Evans, S. Development (2005) [Pubmed]
  23. N-myc transgene promotes B lymphoid proliferation, elicits lymphomas and reveals cross-regulation with c-myc. Rosenbaum, H., Webb, E., Adams, J.M., Cory, S., Harris, A.W. EMBO J. (1989) [Pubmed]
  24. Juxtaposition of N-myc and Ig kappa through a reciprocal t(6;12) translocation in a mouse plasmacytoma. Axelson, H., Wang, Y., Silva, S., Mattei, M.G., Klein, G. Genes Chromosomes Cancer (1994) [Pubmed]
  25. IgH enhancer-mediated deregulation of N-myc gene expression in transgenic mice: generation of lymphoid neoplasias that lack c-myc expression. Dildrop, R., Ma, A., Zimmerman, K., Hsu, E., Tesfaye, A., DePinho, R., Alt, F.W. EMBO J. (1989) [Pubmed]
  26. N-myc is frequently activated by proviral insertion in MuLV-induced T cell lymphomas. van Lohuizen, M., Breuer, M., Berns, A. EMBO J. (1989) [Pubmed]
  27. N-myc-dependent repression of ndr1, a gene identified by direct subtraction of whole mouse embryo cDNAs between wild type and N-myc mutant. Shimono, A., Okuda, T., Kondoh, H. Mech. Dev. (1999) [Pubmed]
  28. Cooperation of Myb and Myc proteins in T cell lymphomagenesis. Davies, J., Badiani, P., Weston, K. Oncogene (1999) [Pubmed]
  29. Expression of myc-family, myc-interacting, and myc-target genes during preimplantation mouse development. Domashenko, A.D., Latham, K.E., Hatton, K.S. Mol. Reprod. Dev. (1997) [Pubmed]
  30. Development of a two color immunofluorescence stain and immunolocalization method for N-myc and c-myc oncoproteins with a newly generated mouse IgM anti N-myc antibody. Gazitt, Y., He, Y.J., Erdos, G.W., Chang, L., Ashktorab, H., Cohen, R.J. J. Immunol. Methods (1992) [Pubmed]
  31. Contrasting patterns of myc and N-myc expression during gastrulation of the mouse embryo. Downs, K.M., Martin, G.R., Bishop, J.M. Genes Dev. (1989) [Pubmed]
  32. A targeted mutation reveals a role for N-myc in branching morphogenesis in the embryonic mouse lung. Moens, C.B., Auerbach, A.B., Conlon, R.A., Joyner, A.L., Rossant, J. Genes Dev. (1992) [Pubmed]
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