Abstract
Myc protein belongs to Myc family of transcription factors, there are 3 types of Myc: c-Myc, N-Myc, and L-Myc expression by dendritic cells is required for optimal T cell priming. Myc family of transcription factors contain bHLH/LZ (basic Helix-Loop-Helix Leucine Zipper) domain. Through its bHLH domain can bind to DNA, while the leucine zipper domain allows the dimerization with its partner Max, another bHLH transcription factor. Myc protien is a transcription factor that activates expression of many genes through binding on consensus sequences (Enhancer Box sequences (E-boxes)) and recruiting histone acetyltransferase (HATs). The first to be discovered was its capability to drive cell proliferation (upregulates cyclins, downregulates p21), but it also plays a very important role in regulating cell growth (upregulates ribosomal RNA and proteins), apoptosis (downregulates Bcl-2), differentiation, and stem cell self-renewal. Myc is a very strong proto-oncogene and it is very often found to be upregulated in many types of cancers. Myc overexpression stimulates gene amplification, presumably through DNA over-replication. It can also act as a transcriptional repressor. By binding Miz-1 transcription factor and displacing the p300 co-activator, it inhibits expression of Miz-1 target genes. In addition, myc has a direct role in the control of DNA replication. Myc is activated upon various mitogenic signals such as Wnt, Shh and EGF (via the MAPK/ERK pathway). By modifying the expression of its target genes, Myc activation results in numerous biological effects. This paper will provide researchers with a critical appraisal of Myc in cell biology.ary vision/hearing loss. This topic review focused mainly on the side effects and health serious problems with Gardasil vaccine.
Key words: Myc protein; bHLH domain; Cancer; Histone; p300 co-activator
Copyright © 2014 by The American Society for BioMedicine and BM-Publisher, Inc.
- Adhikary S, Marinoni F, Hock A, et al. The ubiquitin ligase HectH9 regulates transcriptional activation by Myc and is essential for tumor cell proliferation. Cell. 2005;123:409–421.
- Ahmadiyeh N, Pomerantz MM, Grisanzio C, et al. 8q24 prostate, breast, and colon cancer risk loci show tissue-specific long-range interaction with MYC. Proc Natl Acad Sci U S A. 2010;107:9742–9746.
- Arvanitis C, Felsher DW. Conditional transgenic models define how MYC initiates and maintains tumorigenesis. Semin Cancer Biol. 2006;16:313–317.
- Beer S, Zetterberg A, Ihrie RA, et al. Developmental Context Determines Latency of MYC-Induced Tumorigenesis. PLoS Biol. 2004;2:E332.
- Brodeur GM, Seeger RC, Schwab M, Varmus HE, Bishop JM. Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage. Science. 1984;224:1121–1124.
- Challagundla KB, Sun XX, Zhang X, DeVine T, Zhang Q, Sears RC, Dai MS. Ribosomal protein L11 recruits miR-24/miRISC to repress c-Myc expression in response to ribosomal stress. Mol Cell Biol. 2011;31:4007–4021.
- Chesi M, Robbiani DF, Sebag M, et al. AID-dependent activation of a MYC transgene induces multiple myeloma in a conditional mouse model of post-germinal center malignancies. Cancer Cell. 2008;13:167–180.
- Cowling VH, Chandriani S, Whitfield ML, Cole MD. A conserved Myc protein domain, MBIV, regulates DNA binding, apoptosis, transformation, and G2 arrest. Mol Cell Biol. 2006;26:4226–4239.
- Dai J, Carver M, Hurley LH, Yang D. Solution Structure of a 2:1 Quindoline-c-MYC G-Quadruplex: Insights into G-Quadruplex-Interactive Small Molecule Drug Design. J Am Chem Soc. 2011;133:17673–17680.
- Andreadi C, Cheung LK, Giblett S, et al. The intermediate-activity (L597V)BRAF mutant acts as an epistatic modifier of oncogenic RAS by enhancing signaling through the RAF/MEK/ERK pathway. Genes Dev. 2012;26:1945–1958.
- Beverly LJ, Varmus HE. MYC-induced myeloid leukemogenesis is accelerated by all six members of the antiapoptotic BCL family. Oncogene. 2009;28:1274–1279.
- Bollag G, Hirth P, Tsai J, et al. Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma. Nature. 2010;467:596–599.
- Beaulieu ME, McDuff FO, Bedard M, Montagne M, Lavigne P. Methods for the expression, purification, preparation, and biophysical characterization of constructs of the c-Myc and Max b-HLH-LZs. Methods Mol Biol. 2013;1012:7–20.
- Sharrard RMRJ, Rogers S, Shorthouse AJ. Patterns of methylation of the c-myc gene in human colorectal cancer progression. Br J Cancer. 1992;65(5):667–72.
- Clausen DM, Guo J, Parise RA, Beumer JH, Egorin MJ, Lazo JS, Prochownik EV, Eiseman JL. In vitro cytotoxicity and in vivo efficacy, pharmacokinetics, and metabolism of 10074-G5, a novel small-molecule inhibitor of c-Myc/Max dimerization. J Pharmacol Exp Ther. 2010;335(3):715–27.
- Dang CV. Therapeutic targeting of Myc-reprogrammed cancer cell metabolism. Cold Spring Harb Symp Quant Biol. 2011;76:369–74.
- Kota J, Chivukula RR, O'Donnell KA, Wentzel EA, Montgomery CL, Hwang HW, Chang TC, Vivekanandan P, Torbenson M, Clark KR, et al. Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell. 2009;137(6):1005–17.
- Wang X, Cunningham M, Zhang X, Tokarz S, Laraway B, Troxell M, Sears RC. Phosphorylation regulates c-Myc's oncogenic activity in the mammary gland. Cancer Res. 2011;71(3):925–36.
- Meyer MJ, Das J, Wang X, Yu H. INstruct: a database of high-quality 3D structurally resolved protein interactome networks. Bioinformatics. 2013;29(12):1577–9.
- DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB. The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab. 2008;7(1):11–20.
- Zeller KI, Zhao X, Lee CW, Chiu KP, Yao F, Yustein JT, Ooi HS, Orlov YL, Shahab A, Yong HC, et al. Global mapping of c-Myc binding sites and target gene networks in human B cells. Proc Natl Acad Sci U S A. 2006;103(47):17834–9.
- Yousif NG. Fibronectin promotes migration and invasion of ovarian cancer cells through up‐regulation of FAK–PI 3 K/A kt pathway. Cell biology international 2014;38(1):85-91.
- Menssen A, Hermeking H. Characterization of the c-MYC-regulated transcriptome by SAGE: identification and analysis of c-MYC target genes. Proc Natl Acad Sci U S A. 2002;99(9):6274–9.
- Corzo C, Corominas JM, Tusquets I, Salido M, Bellet M, Fabregat X, Serrano S, Sole F. The MYC oncogene in breast cancer progression: from benign epithelium to invasive carcinoma. Cancer Genet Cytogenet. 2006;165(2):151–6.
- Aulmann S, Adler N, Rom J, Helmchen B, Schirmacher P, Sinn HP. c-myc amplifications in primary breast carcinomas and their local recurrences. J Clin Pathol. 2006;59(4):424–8.
- Dang CV, Kim JW, Gao P, Yustein J. The interplay between MYC and HIF in cancer. Nat Rev Cancer. 2008;8:51–56.
- Dai J, Carver M, Hurley LH, Yang D. Solution Structure of a 2:1 Quindoline-c-MYC G-Quadruplex: Insights into G-Quadruplex-Interactive Small Molecule Drug Design. J Am Chem Soc. 2011;133:17673–17680.
- Abraham D, Podar K, Pacher M, et al. Raf-1-associated protein phosphatase 2A as a positive regulator of kinase activation. J Biol Chem. 2000;275:22300–22304.
- Andreadi C, Cheung LK, Giblett S , et al. The intermediate-activity (L597V)BRAF mutant acts as an epistatic modifier of oncogenic RAS by enhancing signaling through the RAF/MEK/ERK pathway. Genes Dev. 2012;26:1945–1958.
- Balasubramanian S, Hurley LH, Neidle S. Targeting G-quadruplexes in gene promoters: a novel anticancer strategy? Nat Rev Drug Discov. 2011;10:261–275.
- Beverly LJ, Varmus HE. MYC-induced myeloid leukemogenesis is accelerated by all six members of the antiapoptotic BCL family. Oncogene. 2009;28:1274–1279.
- Blackwood EM, Eisenman RN. Max: a helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with Myc. Science. 1991;251:1211–1217.
- Boone DN, Qi Y, Li Z, Hann SR. Egr1 mediates p53-independent c-Myc-induced apoptosis via a noncanonical ARF-dependent transcriptional mechanism. Proc Natl Acad Sci USA. 2011;108:632–637.
- Cairo S, Wang Y, de Reyniès A, et al. Stem cell-like micro-RNA signature driven by Myc in aggressive liver cancer. Proc Natl Acad Sci USA. 2010;107:20471–20476.
- Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364:2507–2516.
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DOI: http://dx.doi.org/10.18081/2333-5106/014-07/147-159
American Journal of BioMedicine 2014, Volume 2, Issue 3, pages 147-159
Received March 30, 2014; accepted June 13, 2014, Published July 14, 2014
How to cite this article
Bandeira MH, Ribeiro CT. Myc protein: function, pathway and mutation. American Journal of BioMedicine 2014;2(3):147-159.
Case report outline
1. Abstract
2. Keywords
3. Introduction
4. Methods
5. Results
6. Discussion
7. References