Omomyc Reveals New Mechanisms To Inhibit the MYC Oncogene

REFERENCES

• Meyer N, Penn LZ. 2008. Reflecting on 25 years of Myc. Nat Rev Cancer 8:976–990. https://doi.org/10.1038/nrc2231.
   PubMed Web of Science ®Google Scholar
• Wasylishen AR, Penn LZ. 2010. Myc: the Beauty and the Beast. Genes Cancer 1:532–541. https://doi.org/10.1177/1947601910378024.
   PubMedGoogle Scholar
• Dang CV. 2012. MYC on the path to cancer. Cell 149:22–35. https://doi.org/10.1016/j.cell.2012.03.003.
   PubMed Web of Science ®Google Scholar
• Kato GJ, Barret J, Villa-Garcia M, Dang CV. 1990. An amino-terminal c-Myc domain required for neoplastic transformation activates transcription. Mol Cell Biol 10:5914–5920. https://doi.org/10.1128/MCB.10.11.5914.
   PubMed Web of Science ®Google Scholar
• Blackwell TK, Kretzner L, Blackwood EM, Eisenman RN, Weintraub H. 1990. Sequence specific DNA binding by c-Myc protein. Science 250:1149–1151. https://doi.org/10.1126/science.2251503.
   PubMed Web of Science ®Google Scholar
• Halazonetis TD, Kandil AN. 1991. Determination of the c-MYC DNA-binding site. Proc Natl Acad Sci U S A 88:6162–6166. https://doi.org/10.1073/pnas.88.14.6162.
   PubMedGoogle Scholar
• Blackwood EM, Eisenman RN. 1991. Max: a helix-loop-helix protein that forms a sequence specific DNA-binding complex with Myc. Science 251:1211–1217. https://doi.org/10.1126/science.2006410.
   PubMed Web of Science ®Google Scholar
• Amanti B, Brooks MW, Levy N, Littlewood TD, Evans GI, Land H. 1993. Oncogenic activity of the c-Myc protein requires dimerization with Max. Cell 72:233–245. https://doi.org/10.1016/0092-8674(93)90663-B.
   PubMed Web of Science ®Google Scholar
• Fernandez PC, Frank SB, Wang L, Schroeder M, Liu S, Greene J, Cocito A, Amati B. 2003. Genomic targets of the human c-Myc protein. Genes Dev 17:1115–1129. https://doi.org/10.1101/gad.1067003.
   PubMed Web of Science ®Google Scholar
• Thomas LR, Wang Q, Grieb BC, Phan J, Foshage AM, Sun Q, Olejniczak ET, Clark T, Dey S, Lorey S, Alicie B, Howard GC, Cawthon B, Ess KC, Eischen CM, Zhao Z, Fesik SW, Tansey WP. 2015. Interaction with WDR5 promotes target gene recognition and tumorigenesis by MYC. Mol Cell 58:440–452. https://doi.org/10.1016/j.molcel.2015.02.028.
   PubMed Web of Science ®Google Scholar
• Lorenzin F, Benary U, Baluapuri A, Walz S, Jung LA, von Eyss B, Kisker C, Wolf J, Eilers M, Wolf E. 2016. Different promoter affinities account for specificity in Myc-dependent gene regulation. ELife 5:e15161. https://doi.org/10.7554/eLife.15161.
   Google Scholar
• Whitfield J, Beaulieu M-E, Soucek L. 2017. Strategies to inhibit Myc and their clinical applicability. Front Cell Dev Biol 5:10. https://doi.org/10.3389/fcell.2017.00010.
   PubMed Web of Science ®Google Scholar
• Luscher B. 2012. MAD1 and its life as a MYC antagonist: an update. Eur J Cell Biol 91:506–514. https://doi.org/10.1016/j.ejcb.2011.07.005.
   PubMed Web of Science ®Google Scholar
• Xu D, Popov N, Hou M, Wang Q, Bjorkholm M, Gruber A, Menkel AR, Henriksson A. 2001. Switch from Myc/Max to Mad1/Max binding and decrease in histone acetylation at the telomerase reverse transcriptase promoter during differentiation of HL60 cells. Proc Natl Acad Sci U S A 98:3826–3831. https://doi.org/10.1073/pnas.071043198.
   PubMed Web of Science ®Google Scholar
• Okada M, Miller TC, Wen L, Shi Y-B. 2017. A balance of Mad and Myc expression dictates larval cell apoptosis and adult stem cell development during Xenopus intestinal metamorphosis. Cell Death Dis 8:e2787. https://doi.org/10.1038/cddis.2017.198.
   PubMed Web of Science ®Google Scholar
• Zhu J, Blenis J, Yuan J. 2008. Activation of PI3K/Akt and MAPK pathways regulates Myc-mediated transcription by phosphorylating and promoting the degradation of Mad1. Proc Natl Acad Sci U S A 105:6584–6589. https://doi.org/10.1073/pnas.0802785105.
   PubMed Web of Science ®Google Scholar
• Poortengs G, Hannan KJ, Snelling H, Walkley C, Jenkins A, Sharkey K, Wall M, Brandenburger Y, Palatsides M, Pearson RB, McArthur GA, Hannan RD. 2004. Mad1 and c-Myc regulate UBF and rDNA transcription during granulocyte differentiation. EMBO J 23:3325–3335. https://doi.org/10.1038/sj.emboj.7600335.
   PubMed Web of Science ®Google Scholar
• Ayer DE, Lawrence QA, Eisenman RN. 1995. Mad-Max transcriptional repression is mediated by ternary complex formation with mammalian homolog of yeast repressor Sin3. Cell 80:767–776. https://doi.org/10.1016/0092-8674(95)90355-0.
   PubMed Web of Science ®Google Scholar
• Lafita-Navarro MDC, Blanco R, Mata-Garrido J, Liaño-Pons J, Tapia O, García-Gutiérrez L, García-Alegría E, Berciano MT, Lafarga M, León J. 2016. MXD1 localizes in the nucleolus, binds UBF, and impairs rRNA synthesis. Oncotarget 7:69536–69548. https://doi.org/10.18632/oncotarget.11766.
   PubMedGoogle Scholar
• Soucek L, Helmer-Citterich M, Sacco A, Jucker R, Cesareni G, Nasi S. 1998. Design and properties of a Myc derivative tat efficiently homodimerizes. Oncogene 17:2463–2472. https://doi.org/10.1038/sj.onc.1202199.
   PubMed Web of Science ®Google Scholar
• Savino M, Annibali D, Carucci N, Favuzzi E, Cole MD, Evan GI, Soucek L, Nasi S. 2011. The action mechanism of the Myc inhibitor termed Omomyc may give clues on how to target Myc for cancer therapy. PLoS One 6:e22284. https://doi.org/10.1371/journal.pone.0022284.
   Web of Science ®Google Scholar
• Soucek L, Whitfield JR, Sodir NM, Massó-Vallés D, Serrano E, Karnezis AN, Swigart LB, Evan GI. 2013. Inhibition of Myc family proteins eradicates KRas-driven lung cancer in mice. Genes Dev 27:504–513. https://doi.org/10.1101/gad.205542.112.
   PubMed Web of Science ®Google Scholar
• Jung LA, Gebhardt A, Koelmel W, Ade CP, Walz S, Kuper J, von Eyss B, Letschert S, Redel C, d’Artista L, Biankin A, Zender L, Sauer M, Wolf E, Evan G, Kisker C, Eilers M. 2017. OmoMYC blunts promoter invasion by oncogenic Myc to inhibit gene expression characteristic of Myc-dependent tumors. Oncogene 36:1911–1924. https://doi.org/10.1038/onc.2016.354.
   PubMed Web of Science ®Google Scholar
• Xu J, Chen G, De Jong AT, Shahravan SH, Shin JA. 2009. Max-E47, a designed minimalist protein that targets the E-box site in vivo and in vitro. J Am Chem Soc 131:7839–7848. https://doi.org/10.1021/ja901306q.
   PubMed Web of Science ®Google Scholar
• Lustig LC, Dingar D, Tu WB, Lourenco C, Kalkat M, Inamoto I, Ponzielli R, Chan WCW, Shin JA, Penn LZ. 2017. Inhibiting Myc binding to E-box DNA motif by ME47 decreases tumor xenograft growth. Oncogene 36:6830–6837. https://doi.org/10.1038/onc.2017.275.
   PubMed Web of Science ®Google Scholar
• Beaulieu M-E, Jausset T, Masso-Valles D, Martinez-Martin S, Rahl P, Maltais L, Zacararias-Fluck MF, Casacuberta-Serra S, Serrano del Pozo E, Fiore C, Foradada L, Castillo Cano V, Sanchez-Hervas M, Guenther M, Romero Sanz E, Oteo M, Tremblay C, Martin G, Letourneau D, Montagne M, Morcillo Alonso MA, Whitfield JR, Lavigne P, Soucek L. 2019. Intrinsic cell-penetrating activity propels proof of concept to viable anti-MYC therapy. Sci Transl Med 11:eaar5012. https://doi.org/10.1126/scitranslmed.aar5012.
   PubMed Web of Science ®Google Scholar
• Casey SC, Tong L, Li Y, Do R, Walz S, Fitzgerald KN, Gouw AM, Baylot V, Gutgemann I, Eilers M, Felsher DW. 2016. MYC regulates the anti-tumor immune response through CD47 and PD-L1. Science 352:227–231. https://doi.org/10.1126/science.aac9935.
   PubMed Web of Science ®Google Scholar
• Emmerich CH, Cohen P. 2015. Optimising methods for the preservation, capture and identification of ubiquitin chains and ubiquitylated proteins by immunoblotting. Biochem Biophys Res Commun 466:1–14. https://doi.org/10.1016/j.bbrc.2015.08.109.
   PubMed Web of Science ®Google Scholar
• Martinez Molina D, Nordlund P. 2016. The cellular thermal shift assay: a novel biophysical assay for in situ drug target engagement and mechanistic biomarker studies. Annu Rev Pharmacol Toxicol 56:141–161. https://doi.org/10.1146/annurev-pharmtox-010715-103715.
   PubMed Web of Science ®Google Scholar
• Ueshima S, Nagata K, Okuwaki M. 2017. Internal associations of the acidic region of upstream binding factor control its nucleolar localization. Mol Cell Biol 37:e00218-17. https://doi.org/10.1128/MCB.00218-17.
   Google Scholar
• Grandori C, Gomez-Roman N, Felton-Edkins ZA, Ngouenet C, Galloway DA, Eisenman RN, White RJ. 2005. c-Myc binds to human ribosomal DNA and stimulates transcription of rRNA genes by RNA polymerase I. Nat Cell Biol 7:311–318. https://doi.org/10.1038/ncb1224.
   PubMed Web of Science ®Google Scholar
• Halbach A, Zhang H, Wengi A, Jablonska Z, Gruber IML, Halbeisen RE, Dehé P-M, Kemmeren P, Holstege F, Géli V, Gerber AP, Dichtl B. 2009. Cotranslational assembly of yeast SET1C histone methyltransferase complex. EMBO J 28:2959–2970. https://doi.org/10.1038/emboj.2009.240.
   PubMed Web of Science ®Google Scholar
• Duncan CDS, Mata J. 2011. Widespread cotranslational formation of protein complexes. PLoS Genet 7:e1002398. https://doi.org/10.1371/journal.pgen.1002398.
   PubMed Web of Science ®Google Scholar
• Ullius A, Luscher-Firzlaff J, Costa IG, Walsemann G, Forst AH, Gusmao EG, Kapelle K, Kleine H, Kremmer E, Vervoorts J, Luscher B. 2014. The interaction of MYC with the Trithorax protein ASH2L promotes gene transcription by regulating H3K27 modification. Nucleic Acids Res 42:6901–6920. https://doi.org/10.1093/nar/gku312.
   PubMed Web of Science ®Google Scholar
• Choi SH, Wright JB, Gerber SA, Cole MD. 2010. Myc protein is stabilized by a novel E3 ligase. Genes Dev 24:1236–1241. https://doi.org/10.1101/gad.1920310.
   PubMed Web of Science ®Google Scholar
• Wells JN, Bergendahl T, Marsh JA. 2015. Co-translational assembly of protein complexes. Biochem Soc Trans 43:1221–1226. https://doi.org/10.1042/BST20150159.
   PubMed Web of Science ®Google Scholar
• Hu J, Banerjee A, Goss D. 2005. Assembly of b/HLH/z proteins c-Myc, Max, and Mad1 with cognate DNA: importance of protein-protein and protein-DNA interactions. Biochemistry 44:11855–11863. https://doi.org/10.1021/bi050206i.
   PubMed Web of Science ®Google Scholar
• Lin CY, Lovén J, Rahl PB, Paranal RM, Burge CB, Bradner JE, Lee TI, Young RA. 2012. Transcriptional activation in tumor cells with elevated c-Myc. Cell 151:56–67. https://doi.org/10.1016/j.cell.2012.08.026.
   PubMed Web of Science ®Google Scholar
• Peukert K, Staller P, Schneider A, Carmichael G, Hanel F, Eilers M. 1997. An alternative pathway for gene regulation by Myc. EMBO J 16:5672–5686. https://doi.org/10.1093/emboj/16.18.5672.
   PubMed Web of Science ®Google Scholar
• Nicholls CD, McLure KG, Shields MA, Lee PWK. 2002. Biogenesis of p53 cotranslational dimerization of monomers and posttranslational dimerization of dimers: implications on the dominant negative effect. J Biol Chem 277:12937–12945. https://doi.org/10.1074/jbc.M108815200.
   PubMed Web of Science ®Google Scholar
• Wiese KM, Walz S, von Eyss B, Wolf E, Athineos D, Sansom O, Eilers M. 2013. The role of MIZ-1 in MYC-dependent tumorigenesis. Cold Spring Harb Perspect Med 3:a014290. https://doi.org/10.1101/cshperspect.a014290.
   PubMed Web of Science ®Google Scholar
• Herold S, Wanzel M, Beuger V, Frohme C, Beul D, Hillukkala T, Syvaoja J, Saluz H-P, Haenel F, Eilers M. 2002. Negative regulation of the mammalian UV response by Myc through association with Miz-1. Mol Cell 10:509–521. https://doi.org/10.1016/S1097-2765(02)00633-0.
   PubMed Web of Science ®Google Scholar
• Shostak A, Ruppert B, Ha N, Bruns P, Toprak UH, ICGC MMML-Seq Project, Eils R, Sclesner M, Diernfellner A, Brunner M. 2016. Myc/Miz-1-dependent gene repression inversely coordinates the circadian clock with cell cycle and proliferation. Nat Commun 7:11807. https://doi.org/10.1038/ncomms11807.
   PubMed Web of Science ®Google Scholar
• Struntz NB, Chen A, Deutzmann A, Wilson RM, Stefan E, Evans HL, Ramirez MA, Liang T, Caballero F, Wildschut MHE, Neel DV, Freeman DB, Pop MS, McConkey M, Muller S, Curtin BH, Tseng H, Frombach KR, Butty VL, Levine SS, Feau C, Elmiligy S, Hong JA, Lewis TA, Vetere VL, Clemons PA, Malstrom SE, Ebert BL, Lin CY, Felsher DW, Koehler AN. 2019. Stabilization of the Max homodimer by a small molecule attenuates Myc-driven transcription. Cell Chem Biol 26:711.e14–723.e14. https://doi.org/10.1016/j.chembiol.2019.02.009.
   Web of Science ®Google Scholar
• Cox J, Mann M. 2008. MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat Biotechnol 37:1367–1372. https://doi.org/10.1038/nbt.1511.
   Google Scholar
• Cox J, Neuhauser N, Michalski A, Scheltema RA, Olsen JV, Mann M. 2011. Andromeda: a peptide search engine integrated into the MaxQuant environment. J Proteome Res 10:1794–1805. https://doi.org/10.1021/pr101065j.
   PubMed Web of Science ®Google Scholar
• Tyanova S, Temu T, Sinitcyn P, Carlson A, Hein MY, Geiger T, Mann M, Cox J. 2016. The Perseus computational platform for comprehensive analysis of (prote)omics data. Nat Methods 13:731–740. https://doi.org/10.1038/nmeth.3901.
   PubMed Web of Science ®Google Scholar
• Heiman M, Kulicke R, Fenster RJ, Greengard P, Heintz N. 2014. Cell-type specific mRNA purification by translating ribosome affinity purification. Nat Protoc 9:1282–1291. https://doi.org/10.1038/nprot.2014.085.
   PubMed Web of Science ®Google Scholar
• Piparia R, Ouellette D, Stine WB, Grinnell C, Tarcsa E, Radziejewski C, Correia I. 2012. A high throughput capillary electrophoresis method to obtain pharmacokinetics and quality attributes of a therapeutic molecule in circulation. MAbs 4:521–531. https://doi.org/10.4161/mabs.20099.
   PubMed Web of Science ®Google Scholar
• Brunn N, Mauze S, Gu D, Wiswell D, Ueda R, Hodges D, Beebe AM, Zhang S, Escandon E. 2016. The role of anti-drug antibodies in the pharmacokinetics, disposition, target engagement, and efficacy of a GITR agonist monoclonal antibody in mice. J Pharm Exp Ther 356:574–586. https://doi.org/10.1124/jpet.115.229864.
   PubMed Web of Science ®Google Scholar