N-Myc
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| Location (UCSC) | Chr 2: 15.94 – 15.95 Mb | Chr 12: 12.99 – 12.99 Mb | |||||||
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N-myc proto-oncogene protein also known as N-Myc or basic helix-loop-helix protein 37 (bHLHe37), is a protein that in humans is encoded by the MYCN gene.
Function
The MYCN gene is a member of the MYC family of
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.
Clinical significance
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.[10][11][12] MYCN can also be activated in neuroblastoma and other cancers through somatic mutation.[13] Intriguingly, recent genome-wide H3K27ac profiling in patient-derived NB samples revealed four distinct SE-driven epigenetic subtypes, characterized by their own and specific master regulatory networks. Three of them are named after the known clinical groups: MYCN-amplified, MYCN non-amplified high-risk, and MYCN non-amplified low-risk NBs, while the fourth displays cellular features which resemble multipotent Schwann cell precursors. Interestingly, the cyclin gene CCND1 was regulated through distinct and shared SEs in the different subtypes, and, more importantly, some tumors showed signals belonging to multiple epigenetic signatures, suggesting that the epigenetic landscape is likely to contribute to intratumoral heterogeneity. [14]
Interactions
N-Myc has been shown to
N-Myc is also stabilized by
Being independent from MYCN/MAX interaction, MYCN is also a transcriptional co-regulator of p53 in MYCN-amplified neuroblastoma.[citation needed] MYCN alters transcription of p53 target genes which regulate apoptosis responses and DNA damage repair in cell cycle. This MYCN-p53 interaction is through exclusive binding of MYCN to C-terminal domains of tetrameric p53. As a post-translational modification, MYCN binding to C-terminal domains of tetrameric p53 impacts p53 promoter selectivity and interferes other cofactors binding to this region.[19]
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000134323 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000037169 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Entrez Gene: MYCN v-myc myelocytomatosis viral related oncogene, neuroblastoma derived (avian)".
- PMID 12381668.
- PMID 1419902.
- ^ "MYCN opposite strand/antisense RNA [Homo sapiens]". Entrez Gene Database. National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 24391509.
- S2CID 1620573.
- PMID 2582423.
- PMID 6719137.
- PMID 23334666.
- PMID 34884690.
- PMID 2006410.
- PMID 10229200.
- PMID 19111882.
- PMID 25175806.
- PMID 22606048.
Further reading
- Lüscher B (2001). "Function and regulation of the transcription factors of the Myc/Max/Mad network". Gene. 277 (1–2): 1–14. PMID 11602341.
- Hagiwara T, Nakaya K, Nakamura Y, Nakajima H, Nishimura S, Taya Y (1992). "Specific phosphorylation of the acidic central region of the N-myc protein by casein kinase II". Eur. J. Biochem. 209 (3): 945–50. PMID 1425701.
- Fougerousse F, Meloni R, Roudaut C, Beckmann JS (1992). "Dinucleotide repeat polymorphism at the human hemoglobin alpha-1 pseudo-gene (HBAP1)". Nucleic Acids Res. 20 (5): 1165. PMID 1549498.
- Krystal GW, Armstrong BC, Battey JF (1990). "N-myc mRNA forms an RNA-RNA duplex with endogenous antisense transcripts". Mol. Cell. Biol. 10 (8): 4180–91. PMID 1695323.
- Blackwood EM, Eisenman RN (1991). "Max: a helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with Myc". Science. 251 (4998): 1211–7. PMID 2006410.
- Emanuel BS, Balaban G, Boyd JP, Grossman A, Negishi M, Parmiter A, Glick MC (1985). "N-myc amplification in multiple homogeneously staining regions in two human neuroblastomas". Proc. Natl. Acad. Sci. U.S.A. 82 (11): 3736–40. PMID 2582423.
- Ibson JM, Rabbitts PH (1988). "Sequence of a germ-line N-myc gene and amplification as a mechanism of activation". Oncogene. 2 (4): 399–402. PMID 2834684.
- Stanton LW, Schwab M, Bishop JM (1986). "Nucleotide sequence of the human N-myc gene". Proc. Natl. Acad. Sci. U.S.A. 83 (6): 1772–6. PMID 2869488.
- Michitsch RW, Melera PW (1985). "Nucleotide sequence of the 3' exon of the human N-myc gene". Nucleic Acids Res. 13 (7): 2545–58. PMID 2987858.
- Slamon DJ, Boone TC, Seeger RC, Keith DE, Chazin V, Lee HC, Souza LM (1986). "Identification and characterization of the protein encoded by the human N-myc oncogene". Science. 232 (4751): 768–72. PMID 3008339.
- Garson JA, van den Berghe JA, Kemshead JT (1987). "Novel non-isotopic in situ hybridization technique detects small (1 Kb) unique sequences in routinely G-banded human chromosomes: fine mapping of N-myc and beta-NGF genes". Nucleic Acids Res. 15 (12): 4761–70. PMID 3299258.
- Stanton LW, Bishop JM (1988). "Alternative processing of RNA transcribed from NMYC". Mol. Cell. Biol. 7 (12): 4266–72. PMID 3437890.
- Kohl NE, Legouy E, DePinho RA, Nisen PD, Smith RK, Gee CE, Alt FW (1986). "Human N-myc is closely related in organization and nucleotide sequence to c-myc". S2CID 4344361.
- Grady EF, Schwab M, Rosenau W (1987). "Expression of N-myc and c-src during the development of fetal human brain". Cancer Res. 47 (11): 2931–6. PMID 3552210.
- Ramsay G, Stanton L, Schwab M, Bishop JM (1987). "Human proto-oncogene N-myc encodes nuclear proteins that bind DNA". Mol. Cell. Biol. 6 (12): 4450–7. PMID 3796607.
- Brodeur GM, Seeger RC (1986). "Gene amplification in human neuroblastomas: basic mechanisms and clinical implications". Cancer Genet. Cytogenet. 19 (1–2): 101–11. PMID 3940169.
- Kanda N, Schreck R, Alt F, Bruns G, Baltimore D, Latt S (1983). "Isolation of amplified DNA sequences from IMR-32 human neuroblastoma cells: facilitation by fluorescence-activated flow sorting of metaphase chromosomes". Proc. Natl. Acad. Sci. U.S.A. 80 (13): 4069–73. PMID 6575396.
- Schwab M, Varmus HE, Bishop JM, Grzeschik KH, Naylor SL, Sakaguchi AY, Brodeur G, Trent J (1984). "Chromosome localization in normal human cells and neuroblastomas of a gene related to c-myc". Nature. 308 (5956): 288–91. S2CID 4333762.
External links
- MYCN+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.