MYC From: Wikipedia Nicholas Britt (Wikipedia, 2008)

c-Myc translocations were initially found in Burkitt’s Lymphoma Translocates to chromosome 14, where it attaches near the promoter region of of heavy-chain Ig Translocation breakpoints in Burkitt's lymphoma. (a) An example of the typical t(8;14) translocation of c-myc into the immunoglobulin heavy chain locus is shown with the chromo- some 8 breakpoint 59 of the c-myc gene and the chromosome 14 breakpoint in the VDJ region. Left: Dalla-Revera Right:Boxer and Dang (Dalla-Favera et al., 1982) (Boxer & Dang, 2001)

MYC gene is regulated and activated by multiple pathways Dang (Dang, 2012)

c-Myc dimerizes with Max and binds to DNA at E-boxes The MYC family of proteins is a group of basic-helix-loop-helix-leucine zipper transcription factors that feature prominently in cancer. Overexpression of MYC is observed in the vast majority of human malignancies and promotes an extraordinary set of changes that impact cell proliferation, growth, metabolism, DNA replication, cell cycle progression, cell adhesion, differentiation, and metastasis. (Tansey) Left is Tansey, right is Dang (Dang, 2012) (Tansey, 2014)

c-Myc promotes many cellular and molecular processes Miller 2012 (Miller, 2012)

c-Myc activity is dependent on its concentration within the nucleus Favors the binding of Myc-Max to E box genes to regulate metabolism and and genes involved in ribosomal biogenesis and cell mass accumulation The canonical Myc E box 50-CACGTG-30 is among the most frequently occurring DNA-binding motifs in the human genome (Xie et al., 2005). This motif, however, could be bound by different transcription factors such as ChREBP, SREBP, HIF-1, NRF1, USF, TFE3, Clock, and Bmal (Figure 4). It stands to reason that in nonproliferating cells, non-Myc E box transcription factors regulate basal metabolism to maintain cellular structural and functional integrity. When cells are stimulated to proliferate, Myc levels rise, permitting Myc to occupy E box-driven genes normally bound by other transcription factors and activate a program of biomass accumulation and enhanced cellular bioenergetics. Dang (Dang, 2012)

c-Myc becomes oncogenic through chromosomal translocation Boxer and Dang (Boxer & Dang, 2001)

c-Myc inactivation in mice causes tumor arrest and regression Complete removal of c-myc results in slowed cell growth and proliferation, suggesting that while c-myc is not required for cell proliferation, it acts as an integrator and accelerator of cellular metabolism and proliferation Arvantis (Arvantis & Felsher, 2006)

BET/BDR4 bromodomain inhibitor JQ1 prevents c-Myc driven tumor progression in vitro and in vivo A bromodomain is an approximately 110 amino acid protein domain that recognizes acetylated lysine residues, such as those on the N-terminal tails of histones. Bromodomains, as the "readers" of lysine acetylation, are responsible in transducing the signal carried by acetylated lysine residues and translating it into various normal or abnormal phenotypes.[2] c-Myc transcription is associated locally and globally with increases in histone lysine side-chain acetylation, a covalent modification of chromatin that is regionally associated with transcriptional activation Delmore (Delmore et al., 2011)

Sources Arvanitis, C., & Felsher, D. W. (2006, August). Conditional transgenic models define how MYC initiates and maintains tumorigenesis. In Seminars in cancer biology (Vol. 16, No. 4, pp. 313-317). Academic Press. Boxer, L. M., & Dang, C. V. (2001). Translocations involving c-myc and c-myc function. Oncogene, 20(40), 5595. Dalla-Favera, R., Bregni, M., Erikson, J., Patterson, D., Gallo, R. C., & Croce, C. M. (1982). Human c-myc onc gene is located on the region of chromosome 8 that is translocated in Burkitt lymphoma cells. Proceedings of the National Academy of Sciences, 79(24), 7824-7827. Dang, C. V. (2012). MYC on the path to cancer. Cell, 149(1), 22-35. Delmore, J. E., Issa, G. C., Lemieux, M. E., Rahl, P. B., Shi, J., Jacobs, H. M., ... & Chesi, M. (2011). BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell, 146(6), 904-917. Miller, D. M., Thomas, S. D., Islam, A., Muench, D., & Sedoris, K. (2012). c-Myc and cancer metabolism. Tansey, W. P. (2014). Mammalian MYC proteins and cancer. New Journal of Science, 2014. https://en.wikipedia.org/wiki/Myc Wikipedia source is just for the image on the title page