The MYCN gene is a member of the MYC family of transcription factors and encodes a protein with a basic helix-loop-helix (bHLH) domain. This protein is located in the cell nucleus and must dimerize with another bHLH protein in order to bind DNA. N-Myc is highly expressed in the fetal brain and is critical for normal brain development.
The MYCN gene has an antisense RNA, N-cym or MYCNOS, transcribed from the opposite strand which can be translated to form a protein product. N-Myc and MYCNOS are co-regulated both in normal development and in tumor cells, so it is possible that the two proteins are functionally related.
Amplification and overexpression of N-Myc can lead to tumorigenesis. Excess N-Myc is associated with a variety of tumors, most notably neuroblastomas where patients with amplification of the N-Myc gene tend to have poor outcomes.
N-Myc is also stabilized by aurora A which protects it from degradation. Drugs that target this interaction are under development, and are designed to change the conformation of aurora A in order to cause degradation of N-Myc.
^Knoepfler PS, Cheng PF, Eisenman RN (2002). "N-myc is essential during neurogenesis for the rapid expansion of progenitor cell populations and the inhibition of neuronal differentiation.". Genes Dev.16 (20): 2699–712. doi:10.1101/gad.1021202. PMID12381668.
^Armstrong BC, Krystal GW (1992). "Isolation and characterization of complementary DNA for N-cym, a gene encoded by the DNA strand opposite to N-myc.". Cell Growth Differ.3 (6): 385–90. PMID1419902.
^Cheng JM, Hiemstra JL, Schneider SS, Naumova A, Cheung NK, Cohn SL, Diller L, Sapienza C, Brodeur GM (June 1993). "Preferential amplification of the paternal allele of the N-myc gene in human neuroblastomas". Nat. Genet.4 (2): 191–4. doi:10.1038/ng0693-191. PMID8102299.
^Brodeur GM, Seeger RC, Schwab M, Varmus HE, Bishop JM (1984). "Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage.". Science224 (4653): 1121–4. doi:10.1126/science.6719137. PMID6719137.
^Blackwood EM, Eisenman RN (March 1991). "Max: a helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with Myc". Science251 (4998): 1211–7. doi:10.1126/science.2006410. PMID2006410.
^FitzGerald MJ, Arsura M, Bellas RE, Yang W, Wu M, Chin L, Mann KK, DePinho RA, Sonenshein GE (April 1999). "Differential effects of the widely expressed dMax splice variant of Max on E-box vs initiator element-mediated regulation by c-Myc". Oncogene18 (15): 2489–98. doi:10.1038/sj.onc.1202611. PMID10229200.
^Otto T, Horn S, Brockmann M, Eilers U, Schüttrumpf L, Popov N, Kenney AM, Schulte JH, Beijersbergen R, Christiansen H, Berwanger B, Eilers M (January 2009). "Stabilization of N-Myc is a critical function of Aurora A in human neuroblastoma". Cancer Cell15 (1): 67–78. doi:10.1016/j.ccr.2008.12.005. PMID19111882.
^Gustafson WC, Meyerowitz JG, Nekritz EA, Chen J, Benes C, Charron E, Simonds EF, Seeger R, Matthay KK, Hertz NT, Eilers M, Shokat KM, Weiss WA (Aug 27, 2014). "Drugging MYCN through an Allosteric Transition in Aurora Kinase A.". Cancer cell. PMID25175806.
Blackwood EM, Eisenman RN (1991). "Max: a helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with Myc.". Science251 (4998): 1211–7. doi:10.1126/science.2006410. PMID2006410.
Slamon DJ, Boone TC, Seeger RC, et al. (1986). "Identification and characterization of the protein encoded by the human N-myc oncogene.". Science232 (4751): 768–72. doi:10.1126/science.3008339. PMID3008339.
Schwab M, Varmus HE, Bishop JM, et al. (1984). "Chromosome localization in normal human cells and neuroblastomas of a gene related to c-myc.". Nature308 (5956): 288–91. doi:10.1038/308288a0. PMID6700732.