Abstract
The MYC oncogene was originally identified as a transduced allele (v-myc) in the genome of the highly oncogenic avian retrovirus MC29. The protein product (MYC) of the cellular MYC (c-myc) protooncogene represents the key component of a transcription factor network controlling the expression of a large fraction of all human genes. MYC regulates fundamental cellular processes like growth control, metabolism, proliferation, differentiation, and apoptosis. Mutational deregulation of MYC, leading to increased levels of the MYC protein, is a frequent event in the etiology of human cancers. In this chapter, we describe cell systems and experimental strategies to quantify the oncogenic potential of MYC alleles, to test MYC inhibitors, and to monitor MYC-specific protein–protein interactions that are relevant for the cell transformation process. We also describe experimental procedures to study the evolutionary origin of MYC and to analyze structure, function, and regulation of the ancestral MYC proto-oncogenes.
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References
Duesberg PH, Bister K, Vogt PK (1977) The RNA of avian acute leukemia virus MC29. Proc Natl Acad Sci U S A 74(10):4320–4324. https://doi.org/10.1073/pnas.74.10.4320
Bister K, Hayman MJ, Vogt PK (1977) Defectiveness of avian myelocytomatosis virus MC29: isolation of long-term nonproducer cultures and analysis of virus-specific polypeptide synthesis. Virology 82(2):431–448. https://doi.org/10.1016/0042-6822(77)90017-4
Bister K, Jansen HW (1986) Oncogenes in retroviruses and cells: biochemistry and molecular genetics. Adv Cancer Res 47:99–188. https://doi.org/10.1016/s0065-230x(08)60199-2
Bister K (2012) MC29 avian myelocytomatosis virus. In: Maloy S, Hughes K (eds) Brenner's encylopedia of genetics, vol 4, 2nd edn. Academic Press, San Diego, pp 330–332
Eilers M, Eisenman RN (2008) Myc’s broad reach. Genes Dev 22(20):2755–2766. https://doi.org/10.1101/gad.1712408
Conacci-Sorrell M, McFerrin L, Eisenman RN (2014) An overview of MYC and its interactome. Cold Spring Harb Perspect Med 4(1):a014357. https://doi.org/10.1101/cshperspect.a014357
Stefan E, Bister K (2017) MYC and RAF: key effectors in cellular signaling and major drivers in human cancer. Curr Top Microbiol Immunol 407:117–151. https://doi.org/10.1007/82_2017_4
Dang CV (2012) MYC on the path to cancer. Cell 149(1):22–35. https://doi.org/10.1016/j.cell.2012.03.003
Stine ZE, Walton ZE, Altman BJ, Hsieh AL, Dang CV (2015) MYC, metabolism, and cancer. Cancer Discov 5(10):1024–1039. https://doi.org/10.1158/2159-8290.CD-15-0507
Nesbit CE, Tersak JM, Prochownik EV (1999) MYC oncogenes and human neoplastic disease. Oncogene 18(19):3004–3016. https://doi.org/10.1038/sj.onc.1202746
Gabay M, Li Y, Felsher DW (2014) MYC activation is a hallmark of cancer initiation and maintenance. Cold Spring Harb Perspect Med 4(6):a014241. https://doi.org/10.1101/cshperspect.a014241
Tokheim CJ, Papadopoulos N, Kinzler KW, Vogelstein B, Karchin R (2016) Evaluating the evaluation of cancer driver genes. Proc Natl Acad Sci U S A 113(50):14330–14335. https://doi.org/10.1073/pnas.1616440113
Nair SK, Burley SK (2003) X-ray structures of Myc-max and mad-max recognizing DNA. Molecular bases of regulation by proto-oncogenic transcription factors. Cell 112(2):193–205. https://doi.org/10.1016/s0092-8674(02)01284-9
Wolf E, Lin CY, Eilers M, Levens DL (2015) Taming of the beast: shaping Myc-dependent amplification. Trends Cell Biol 25(4):241–248. https://doi.org/10.1016/j.tcb.2014.10.006
Dang CV (2014) Gene regulation: fine-tuned amplification in cells. Nature 511(7510):417–418. https://doi.org/10.1038/nature13518
Rahl PB, Young RA (2014) MYC and transcription elongation. Cold Spring Harb Perspect Med 4(1):a020990. https://doi.org/10.1101/cshperspect.a020990
Gallant P, Shiio Y, Cheng PF, Parkhurst SM, Eisenman RN (1996) Myc and Max homologs in Drosophila. Science 274(5292):1523–1527. https://doi.org/10.1126/science.274.5292.1523
Orian A, van Steensel B, Delrow J, Bussemaker HJ, Li L, Sawado T, Williams E, Loo LW, Cowley SM, Yost C, Pierce S, Edgar BA, Parkhurst SM, Eisenman RN (2003) Genomic binding by the Drosophila Myc, Max, Mad/Mnt transcription factor network. Genes Dev 17(9):1101–1114. https://doi.org/10.1101/gad.1066903
Hartl M, Mitterstiller AM, Valovka T, Breuker K, Hobmayer B, Bister K (2010) Stem cell-specific activation of an ancestral myc protooncogene with conserved basic functions in the early metazoan Hydra. Proc Natl Acad Sci U S A 107(9):4051–4056. https://doi.org/10.1073/pnas.0911060107
Young SL, Diolaiti D, Conacci-Sorrell M, Ruiz-Trillo I, Eisenman RN, King N (2011) Premetazoan ancestry of the Myc-Max network. Mol Biol Evol 28(10):2961–2971. https://doi.org/10.1093/molbev/msr132
Hartl M, Glasauer S, Valovka T, Breuker K, Hobmayer B, Bister K (2014) Hydra myc2, a unique pre-bilaterian member of the myc gene family, is activated in cell proliferation and gametogenesis. Biol Open 3(5):397–407. https://doi.org/10.1242/bio.20147005
Hartl M, Puglisi K, Nist A, Raffeiner P, Bister K (2020) The brain acid-soluble protein 1 (BASP1) interferes with the oncogenic capacity of MYC and its binding to calmodulin. Mol Oncol 14(3):625–644. https://doi.org/10.1002/1878-0261.12636
Hartl M, Glasauer S, Gufler S, Raffeiner A, Puglisi K, Breuker K, Bister K, Hobmayer B (2019) Differential regulation of myc homologs by Wnt/beta-catenin signaling in the early metazoan Hydra. FEBS J 286(12):2295–2310. https://doi.org/10.1111/febs.14812
Raffeiner P, Schraffl A, Schwarz T, Röck R, Ledolter K, Hartl M, Konrat R, Stefan E, Bister K (2017) Calcium-dependent binding of Myc to calmodulin. Oncotarget 8(2):3327–3343. https://doi.org/10.18632/oncotarget.13759
Hartl M, Nist A, Khan MI, Valovka T, Bister K (2009) Inhibition of Myc-induced cell transformation by brain acid-soluble protein 1 (BASP1). Proc Natl Acad Sci U S A 106(14):5604–5609. https://doi.org/10.1073/pnas.0812101106
Hart JR, Garner AL, Yu J, Ito Y, Sun M, Ueno L, Rhee JK, Baksh MM, Stefan E, Hartl M, Bister K, Vogt PK, Janda KD (2014) Inhibitor of MYC identified in a Kröhnke pyridine library. Proc Natl Acad Sci U S A 111(34):12556–12561. https://doi.org/10.1073/pnas.1319488111
Raffeiner P, Röck R, Schraffl A, Hartl M, Hart JR, Janda KD, Vogt PK, Stefan E, Bister K (2014) In vivo quantification and perturbation of Myc-Max interactions and the impact on oncogenic potential. Oncotarget 5(19):8869–8878. https://doi.org/10.18632/oncotarget.2588
David CN, MacWilliams H (1978) Regulation of the self-renewal probability in Hydra stem cell clones. Proc Natl Acad Sci U S A 75(2):886–890. https://doi.org/10.1073/pnas.75.2.886
Valovka T, Schönfeld M, Raffeiner P, Breuker K, Dunzendorfer-Matt T, Hartl M, Bister K (2013) Transcriptional control of DNA replication licensing by Myc. Sci Rep 3:3444. https://doi.org/10.1038/srep03444
Acknowledgments
This work was supported by Austrian Science Fund (FWF) grant P23652 (to K.B.), and by the Tyrolean Science Fund (TWF) grant UNI-0404/688 (to M.H.).
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Hartl, M., Bister, K. (2021). MYC Analysis in Cancer and Evolution. In: Soucek, L., Whitfield, J. (eds) The Myc Gene. Methods in Molecular Biology, vol 2318. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1476-1_6
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DOI: https://doi.org/10.1007/978-1-0716-1476-1_6
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