OmoMYC blunts promoter invasion by oncogenic MYC to inhibit gene expression characteristic of MYC-dependent tumors
Open accessAbstract
MYC genes have both essential roles during normal development and exert oncogenic functions during tumorigenesis. Expression of a dominant-negative allele of MYC, termed OmoMYC, can induce rapid tumor regression in mouse models with little toxicity for normal tissues. How OmoMYC discriminates between physiological and oncogenic functions of MYC is unclear. We have solved the crystal structure of OmoMYC and show that it forms a stable homodimer and as such recognizes DNA in the same manner as the MYC/MAX heterodimer. OmoMYC attenuates both MYC-dependent activation and repression by competing with MYC/MAX for binding to chromatin, effectively lowering MYC/MAX occupancy at its cognate binding sites. OmoMYC causes the largest decreases in promoter occupancy and changes in expression on genes that are invaded by oncogenic MYC levels. A signature of OmoMYC-regulated genes defines subgroups with high MYC levels in multiple tumor entities and identifies novel targets for the eradication of MYC-driven tumors.
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Omomyc competes with c-Myc for binding to Max, forming Omomyc/Max complexes that prevent the transcriptional activation of Myc target genes involved in proliferation and metabolism.
“It competes with c-Myc for binding to Max, forming Omomyc/Max complexes that prevent the transcriptional activation of Myc target genes involved in proliferation and metabolism.418–420”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [420]
Omomyc is one of the most studied c-Myc/Max inhibitors, derived from the bHLH structural domain of Myc.
“Omomyc is one of the most studied c-Myc/Max inhibitors, derived from the bHLH structural domain of Myc.”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [420]
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Cites
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625 · see citing works
Inference of macromolecular assemblies from crystalline state.
Krissinel, E., & Henrick, K. (2007) · Journal of Molecular Biology · doi:10.1016/j.jmb.2007.05.022 · Cited by 10,189 · see citing works
Dang, C. V. (2012) · Cell · doi:10.1016/j.cell.2012.03.003 · Cited by 3,390 · see citing works
Redox Regulation of Fos and Jun DNA-Binding Activity in Vitro
Abate, C., Patel, L., Rauscher, F. J., & Curran, T. (1990) · Science · doi:10.1126/science.2118682 · Cited by 1,573 · see citing works
Transcriptional Amplification in Tumor Cells with Elevated c-Myc
Lin, C. Y., Lovén, J., Rahl, P. B., Paranal, R. M., Burge, C. B., Bradner, J. E., Lee, T. I., & Young, R. A. (2012) · Cell · doi:10.1016/j.cell.2012.08.026 · Cited by 1,498 · see citing works
Single-cell analysis reveals a stem-cell program in human metastatic breast cancer cells
Lawson, D. A., Bhakta, N. R., Kessenbrock, K., Prummel, K. D., Yu, Y., Takai, K., Zhou, A. Y., Eyob, H., Balakrishnan, S., Wang, C., et al. (2015) · Nature · doi:10.1038/nature15260 · Cited by 894 · see citing works
Sequence-Specific DNA Binding by the c-Myc Protein
Blackwell, T. K., Kretzner, L., Blackwood, E. M., Eisenman, R. N., & Weintraub, H. M. (1990) · Science · doi:10.1126/science.2251503 · Cited by 863 · see citing works
Modelling Myc inhibition as a cancer therapy
Soucek, L., Whitfield, J. R., Martins, C. P., Finch, A. J., Murphy, D. J., Sodir, N. M., Karnezis, A. N., Swigart, L. B., Nasi, S., & Evan, G. I. (2008) · Nature · doi:10.1038/nature07260 · Cited by 822 · see citing works
Self-citationRecognition by Max of its cognate DNA through a dimeric b/HLH/Z domain
Ferré-D’Amaré, A. R., Prendergast, G. C., Ziff, E. B., & Burley, S. K. (1993) · Nature · doi:10.1038/363038a0 · Cited by 719 · see citing works
An Optimized microRNA Backbone for Effective Single-Copy RNAi
Fellmann, C., Hoffmann, T., Sridhar, V., Hopfgartner, B., Muhar, M., Roth, M., Lai, D. Y., Barbosa, I. A. M., Kwon, J. S., Guan, Y., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.11.020 · Cited by 705 · see citing works
Proteasome subunit Rpn13 is a novel ubiquitin receptor
Husnjak, K., Elsasser, S., Zhang, N., Chen, X., Randles, L., Shi, Y., Hofmann, K., Walters, K. J., Finley, D. J., & Đikić, I. (2008) · Nature · doi:10.1038/nature06926 · Cited by 662 · see citing works
The interplay between MYC and HIF in cancer
Dang, C. V., Kim, J., Gao, P., & Yustein, J. T. (2007) · Nature reviews. Cancer · doi:10.1038/nrc2274 · Cited by 614 · see citing works
Bywater, M. J., Poortinga, G., Sanij, E., Hein, N., Peck, A., Cullinane, C. M., Wall, M., Cluse, L. A., Drygin, D., Anderes, K. L., et al. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.05.019 · Cited by 561 · see citing works
X-Ray Structures of Myc-Max and Mad-Max Recognizing DNA
Nair, S. K., & Burley, S. K. (2003) · Cell · doi:10.1016/s0092-8674(02)01284-9 · Cited by 551 · see citing works
MYC: Connecting selective transcriptional control to global RNA production
Kress, T. R., Sabò, A., & Amati, B. (2015) · Nature reviews. Cancer · doi:10.1038/nrc3984 · Cited by 521 · see citing works
Activation and repression by oncogenic MYC shape tumour-specific gene expression profiles
Walz, S., Lorenzin, F., Morton, J. P., Wiese, K. E., von Eyß, B., Herold, S., Rycak, L., Dumay‐Odelot, H., Karim, S. A., Bartkuhn, M., et al. (2014) · Nature · doi:10.1038/nature13473 · Cited by 502 · see citing works
Self-citationSelective transcriptional regulation by Myc in cellular growth control and lymphomagenesis
Sabò, A., Kress, T. R., Pelizzola, M., de Pretis, S., Gorski, M. M., Tesi, A., Morelli, M. J., Bora, P., Doni, M., Verrecchia, A., et al. (2014) · Nature · doi:10.1038/nature13537 · Cited by 478 · see citing works
Suppression of Myc oncogenic activity by ribosomal protein haploinsufficiency
Barna, M., Pusic, A., Zollo, O., Costa, M. J., Kondrashov, N., Rego, E., Rao, P., & Ruggero, D. (2008) · Nature · doi:10.1038/nature07449 · Cited by 434 · see citing works
Differential Requirements for eIF4E Dose in Normal Development and Cancer
Truitt, M., Conn, C. S., Shi, Z., Pang, X., Tokuyasu, T. A., Coady, A. M., Seo, Y., Barna, M., & Ruggero, D. (2015) · Cell · doi:10.1016/j.cell.2015.05.049 · Cited by 374 · see citing works
Myc-binding-site recognition in the human genome is determined by chromatin context
Guccione, E., Martinato, F., Finocchiaro, G., Luzi, L., Tizzoni, L., Olio, V. D., Zardo, G., Nervi, C., Bernard, L., & Amati, B. B. (2006) · Nature Cell Biology · doi:10.1038/ncb1434 · Cited by 365 · see citing works
Translational Control in Cancer EtiologyPreprint
Ruggero, D. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a012336 · Cited by 362 · see citing works
Global Regulation of Nucleotide Biosynthetic Genes by c-Myc
Liu, Y.-C., Li, F., Handler, J., Huang, C. R. L., Xiang, Y., Neretti, N., Sedivy, J. M., Zeller, K. I., & Dang, C. V. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002722 · Cited by 317 · see citing works
Interaction with WDR5 Promotes Target Gene Recognition and Tumorigenesis by MYC
Thomas, L. R., Wang, Q., Grieb, B. C., Phan, J., Foshage, A. M., Sun, Q., Olejniczak, E. T., Clark, T., Dey, S., Lorey, S., et al. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.02.028 · Cited by 310 · see citing works
Hematopoietic stem cell function and survival depend on c-Myc and N-Myc activity
Laurenti, E., Varnum-Finney, B., Wilson, A., Ferrero, I., Blanco-Bose, W. E., Ehninger, A., Knoepfler, P. S., Cheng, P.-F., MacDonald, H. R., Eisenman, R. N., et al. (2008) · Cell Stem Cell · doi:10.1016/j.stem.2008.09.005 · Cited by 305 · see citing works
Inhibition of Myc family proteins eradicates KRas-driven lung cancer in micePreprint
Soucek, L., Whitfield, J. R., Sodir, N. M., Massó-Vallés, D., Serrano, E., Karnezis, A. N., Swigart, L. B., & Evan, G. I. (2013) · Genes & Development · doi:10.1101/gad.205542.112 · Cited by 299 · see citing works
Self-citationMyc Depletion Induces a Pluripotent Dormant State Mimicking Diapause
Scognamiglio, R., Cabezas-Wallscheid, N., Thier, M. C., Altamura, S., Reyes, A., Prendergast, Á. M., Baumgärtner, D., Carnevalli, L. S., Atzberger, A., Haas, S., et al. (2016) · Cell · doi:10.1016/j.cell.2015.12.033 · Cited by 271 · see citing works
Cunningham, J. T., Moreno, M. V., Lodi, A., Ronen, S. M., & Ruggero, D. (2014) · Cell · doi:10.1016/j.cell.2014.03.052 · Cited by 260 · see citing works
Design and properties of a Myc derivative that efficiently homodimerizes
Soucek, L., Helmer‐Citterich, M., Sacco, A., Jucker, R., Cesareni, G., & Nasi, S. (1998) · Oncogene · doi:10.1038/sj.onc.1202199 · Cited by 224 · see citing works
Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis
Annibali, D., Whitfield, J. R., Favuzzi, E., Jauset, T., Serrano, E., Cuartas, I., Redondo-Campos, S., Folch, G., Gonzàlez-Juncà, A., Sodir, N. M., et al. (2014) · Nature Communications · doi:10.1038/ncomms5632 · Cited by 200 · see citing works
Self-citationTumor Stroma-Derived TGF-β Limits Myc-Driven Lymphomagenesis via Suv39h1-Dependent Senescence
Reimann, M., Lee, S., Loddenkemper, C., Dörr, J. R., Tabor, V., Aichele, P., Stein, H., Dörken, B., Jenuwein, T., & Schmitt, C. A. (2010) · Cancer Cell · doi:10.1016/j.ccr.2009.12.043 · Cited by 184 · see citing works
Endogenous Myc maintains the tumor microenvironmentPreprint
Sodir, N. M., Swigart, L. B., Karnezis, A. N., Hanahan, D., Evan, G. I., & Soucek, L. (2011) · Genes & Development · doi:10.1101/gad.2038411 · Cited by 177 · see citing works
Self-citationGilquin, B., Taillebourg, E., Cherradi, N., Hubstenberger, A., Gay, O., Merle, N., Assard, N., Fauvarque, M.-O., Tomohiro, S., Kuge, O., et al. (2010) · Molecular and Cellular Biology · doi:10.1128/mcb.00007-10 · Cited by 171 · see citing works
Anchoori, R. K., Karanam, B., Peng, S., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.11.001 · Cited by 162 · see citing works
Different promoter affinities account for specificity in MYC-dependent gene regulation
Lorenzin, F., Benary, U., Baluapuri, A., Walz, S., Jung, L. A., von Eyß, B., Kisker, C., Wolf, J., Eilers, M., & Wolf, E. (2016) · eLife · doi:10.7554/elife.15161 · Cited by 162 · see citing works
Self-citationGiuriato, S., Ryeom, S. W., Fan, A. C., Bachireddy, P., Lynch, R. C., Rioth, M. J., van Riggelen, J., Kopelman, A. M., Passegue, E. A., Tang, F. L. M., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0608017103 · Cited by 149 · see citing works
Kress, T. R., Cannell, I. G., Brenkman, A. B., Samans, B., Gaestel, M., Roepman, P., Burgering, B. M. T., Bushell, M., Rosenwald, A., & Eilers, M. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.01.023 · Cited by 146 · see citing works
Self-citationvon Eyß, B., Jaenicke, L. A., Kortlever, R. M., Royla, N., Wiese, K. E., Letschert, S., McDuffus, L., Sauer, M., Rosenwald, A., Evan, G. I., et al. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.10.013 · Cited by 140 · see citing works
Self-citationMichaela, R., Hölzel, M., Thomas, G., Anastassia, M., Thomas, H., Orban, M., Pfisterer, I., Anita, G.-E., Kremmer, E., & Eick, D. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00172-07 · Cited by 139 · see citing works
Taming of the beast: shaping Myc-dependent amplification
Wolf, E., Lin, C. Y., Eilers, M., & Levens, D. (2014) · Trends in Cell Biology · doi:10.1016/j.tcb.2014.10.006 · Cited by 135 · see citing works
Self-citationSavino, M., Annibali, D., Carucci, N., Favuzzi, E., Cole, M. D., Evan, G. I., Soucek, L., & Nasi, S. (2011) · PLoS ONE · doi:10.1371/journal.pone.0022284 · Cited by 129 · see citing works
Self-citationJaenicke, L. A., von Eyß, B., Carstensen, A., Wolf, E., Xu, W., Greifenberg, A. K., Geyer, M., Eilers, M., & Popov, N. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.11.007 · Cited by 110 · see citing works
Self-citationGenome-wide mapping of Myc binding and gene regulation in serum-stimulated fibroblasts
Perna, D., Fagà, G., Verrecchia, A., Gorski, M. M., Barozzi, I., Narang, V., Khng, J., Lim, K., Sung, W.-K., Sanges, R., et al. (2011) · Oncogene · doi:10.1038/onc.2011.359 · Cited by 107 · see citing works
ATPase family AAA domain-containing 3A is a novel anti-apoptotic factor in lung adenocarcinoma cells
Fang, H., Chang, C.-L., Hsu, S., Huang, K. C., Chiang, S., Chiou, S.-H., Huang, C.-H., Hsiao, Y.-T., Lin, T., Chiang, I., et al. (2010) · Journal of Cell Science · doi:10.1242/jcs.062034 · Cited by 106 · see citing works
van Riggelen, J., Müller, J., Otto, T., Beuger, V., Yetil, A., Choi, P. S., Kosan, C., Möröy, T., Felsher, D. W., & Eilers, M. (2010) · Genes & Development · doi:10.1101/gad.585710 · Cited by 105 · see citing works
Self-citationEssential role for Max in early embryonic growth and developmentPreprint
Shen-Li, H., O’Hagan, R. C., Hou, H., Horner, J. W., Lee, H., & DePinho, R. A. (2000) · Genes & Development · doi:10.1101/gad.14.1.17 · Cited by 99 · see citing works
Sequence specificity incompletely defines the genome-wide occupancy of Myc
Guo, J., Li, T., Schipper, J. L., Nilson, K. A., Fordjour, F. K., Cooper, J. J., Gordân, R., & Price, D. H. (2014) · Genome biology · doi:10.1186/s13059-014-0482-3 · Cited by 84 · see citing works
Chung, K. Y., Cheng, I. K.-C., Ching, A. K.-K., et al. (2011) · Hepatology · doi:10.1002/hep.24372 · Cited by 78 · see citing works
C. elegans ATAD-3 Is Essential for Mitochondrial Activity and Development
Hoffmann, M., Bellancé, N., Rossignol, R., Koopman, W. J. H., Willems, P. H. G. M., Mayatepek, E., Bossinger, O., & Distelmaier, F. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007644 · Cited by 70 · see citing works
Interaction with WDR5 Promotes Target Gene Recognition and Tumorigenesis by MYC
Thomas, L. R., Wang, Q., Grieb, B. C., Phan, J., Bryan, A. F., Sun, Q., Olejniczak, E. T., Clark, T. G., Dey, S., Lorey, S. L., et al. (2018) · OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) · doi:10.2210/pdb6dak/pdb · Cited by 64 · see citing works
Contribution of theBOP1 gene, located on 8q24, to colorectal tumorigenesis
Killian, A., Sarafan‐Vasseur, N., Sesboüé, R., Pessot, F. L., Blanchard, F., Lamy, A., Laurent, M., Flaman, J., & Frébourg, T. (2006) · Genes Chromosomes and Cancer · doi:10.1002/gcc.20351 · Cited by 61 · see citing works
An alternative import pathway of AIF to the mitochondria
Chiou, S.-H. (2011) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2011.849 · Cited by 43 · see citing works
Chow, K. (2011) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2011.670 · Cited by 32 · see citing works
Selectivity mechanism of phosphodiesterase isoform inhibitor through in silico investigations
Huang, J., Hu, B., Xu, Z., Ye, Y., Wang, H., Wang, S., Liu, Z. L., & Wang, J. (2021) · Journal of Molecular Modeling · doi:10.1007/s00894-021-04934-7 · Cited by 24 · see citing works
Lorenzin, F., Benary, U., Baluapuri, A., et al. (2016) · doi:10.7554/elife.15161.036 · Cited by 5 · see citing works
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Research works printed but not linked: 2
- 28 Lorenzin F, Benary U, Jung LA, von Eyß B, Walz S, Kisker C et al . Promoter affinity is a critical determinant of the specific gene expression patterns elicited by different MYC levels. eLife 2016; in press.
- 48 Blackwell TK, Kretzner L, Blackwood EM, Eisenman RN, Weintraub H. Sequencespecific DNA binding by the c-myc protein. Science 1990; 250: 1149-1151.
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Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials
Xie, X., Yu, T., Li, X., Zhang, N., Foster, L. J., Peng, C., Huang, W., & He, G. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01589-z · Cited by 396 · see citing works
Carabet, L. A., Rennie, P. S., & Cherkasov, A. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms20010120 · Cited by 172 · see citing works
“Omomyc preferentially forms homodimers that are additionally stabilized by multiple interactions that are not present in the Myc-Max heterodimer, and introduced by specifically designed mutations [80].”
BackgroundInfluentialOmomyc Reveals New Mechanisms To Inhibit the MYC Oncogene
Demma, M. J., Mapelli, C., Sun, A., Bodea, S., Ruprecht, B., Javaid, S., Wiswell, D., Muise, E., Chen, S., Zelina, J., et al. (2019) · Molecular and Cellular Biology · doi:10.1128/mcb.00248-19 · Cited by 92 · see citing works
Beaulieu, M.-E., Martínez-Martín, S., Kaur, J., Castillo Cano, V., Massó-Vallés, D., Foradada Felip, L., López-Estévez, S., Serrano del Pozo, E., Thabussot, H., & Soucek, L. (2023) · Cancers · doi:10.3390/cancers15030826 · Cited by 12 · see citing works
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- Authors
- Jung, L. A., Gebhardt, A., Koelmel, W., Ade, C. P., 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.
- Affiliations
- University of Würzburg (DE)
- Comprehensive Cancer Center Mainfranken (DE)
- Glasgow Royal Infirmary (GB)
- University of Tübingen (DE)
- University of Cambridge (GB)
- Corresponding author
- Kisker, C
- Eilers, M
- Venue
- Oncogene
- Published
- 2016-10-17
- Volume
- 36
- Issue
- 14
- Pages
- 1911-1924
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2534930232
- Cited by
- 101
- References
- 54
- Citations by year
- 2026: 2 · 2025: 10 · 2024: 18 · 2023: 9 · 2022: 6 · 2021: 14 · 2020: 14 · 2019: 16 · 2018: 8 · 2017: 4
- FWCI
- 5.03
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
- HZB Repository (Helmholtz-Zentrum Berlin für Materialien und Energie GmbH (HZB)) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo
- Funders
- Pancreatic Cancer UK (FLF2015_04_GLASGOW)
- Cancer Research UK (17263, 12077, 22585, 19013, 22533)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- Omomyc, c-Myc, Myc-Max heterodimer, chromatin binding, tumor regression
- MeSH terms
- Binding Sites, Cells, Cultured, DNA, Genes, Dominant, Humans, Models, Molecular, Neoplasms, Peptide Fragments, Promoter Regions, Genetic, Gene Expression Regulation, Neoplastic, Proto-Oncogene Proteins c-myc, Sequence Homology, Tumor Suppressor Proteins, Protein Multimerization, Transcriptome
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