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Targeting transcription is no longer a quixotic quest

Nature Chemical Biology volume 11, pages 891–894 (2015)Cite this article

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Misregulated transcription factors play prominent roles in human disease, but their dynamic protein-protein interaction network has long made the goal of transcription-targeted therapeutics impractical. Recent advances in technologies for modulating protein interaction networks mean that the end of the quest is in sight.

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Figure 1: The chemical space of protein-protein interactions.
Figure 2: Transcription complexes are dynamic in composition and conformation.

References

  1. Jacob, F. & Monod, J. J. Mol. Biol. 3, 318–356 (1961).

    Article  CAS  Google Scholar 

  2. Lin, C.Y. et al. Cell 151, 56–67 (2012).

    Article  CAS  Google Scholar 

  3. Pattabiraman, D.R. et al. Blood 123, 2682–2690 (2014).

    Article  CAS  Google Scholar 

  4. Khoo, K.H., Verma, C.S. & Lane, D.P. Nat. Rev. Drug Discov. 13, 217–236 (2014).

    Article  CAS  Google Scholar 

  5. Kar, A. & Gutierrez-Hartmann, A. Crit. Rev. Biochem. Mol. Biol. 48, 522–543 (2013).

    Article  CAS  Google Scholar 

  6. Arkin, M.R., Tang, Y. & Wells, J.A. Chem. Biol. 21, 1102–1114 (2014).

    Article  CAS  Google Scholar 

  7. Thompson, A.D., Dugan, A., Gestwicki, J.E. & Mapp, A.K. ACS Chem. Biol. 7, 1311–1320 (2012).

    Article  CAS  Google Scholar 

  8. Cesa, L.C., Mapp, A.K. & Gestwicki, J.E. Frontiers Bioeng. Biotechnol. 3, 119 (2015).

    Article  Google Scholar 

  9. Fuxreiter, M. et al. Nat. Chem. Biol. 4, 728–737 (2008).

    Article  CAS  Google Scholar 

  10. Hargreaves, D.C. & Crabtree, G.R. Cell Res. 21, 396–420 (2011).

    Article  CAS  Google Scholar 

  11. Krishnamurthy, M. et al. ACS Chem. Biol. 6, 1321–1326 (2011).

    Article  CAS  Google Scholar 

  12. Xie, X. et al. Oncogene 33, 1037–1046 (2014).

    Article  CAS  Google Scholar 

  13. Lee, C.W., Ferreon, J.C., Ferreon, A.C., Arai, M. & Wright, P.E. Proc. Natl. Acad. Sci. USA 107, 19290–19295 (2010).

    Article  CAS  Google Scholar 

  14. Thakur, J.K., Yadav, A. & Yadav, G. Nucleic Acids Res. 42, 2112–2125 (2014).

    Article  CAS  Google Scholar 

  15. Shammas, S.L., Travis, A.J. & Clarke, J. Proc. Natl. Acad. Sci. USA 111, 12055–12060 (2014).

    Article  CAS  Google Scholar 

  16. Law, S.M., Gagnon, J.K., Mapp, A.K. & Brooks, C.L. III. Proc. Natl. Acad. Sci. USA 111, 12067–12072 (2014).

    Article  CAS  Google Scholar 

  17. Wang, N., Lodge, J.M., Fierke, C.A. & Mapp, A.K. Proc. Natl. Acad. Sci. USA 111, 12061–12066 (2014).

    Article  CAS  Google Scholar 

  18. Leonard, S.E., Register, A.C., Krishnamurty, R., Brighty, G.J. & Maly, D.J. ACS Chem. Biol. 9, 1894–1905 (2014).

    Article  CAS  Google Scholar 

  19. Cesa, L.C. et al. ACS Chem. Biol. 8, 1988–1997 (2013).

    Article  CAS  Google Scholar 

  20. Wang, N. et al. J. Am. Chem. Soc. 135, 3363–3366 (2013).

    Article  CAS  Google Scholar 

  21. Majmudar, C.Y. et al. Angew. Chem. 51, 11258–11262 (2012).

    Article  CAS  Google Scholar 

  22. Gee, C.T., Koleski, E.J. & Pomerantz, W.C. Angew. Chem. 54, 3735–3739 (2015).

    Article  CAS  Google Scholar 

  23. Bradner, J.E., McPherson, O.M. & Koehler, A.N. Nat. Protoc. 1, 2344–2352 (2006).

    Article  CAS  Google Scholar 

  24. Pop, M.S. et al. Mol. Cancer Ther. 13, 1492–1502 (2014).

    Article  CAS  Google Scholar 

  25. Niu, S., Rabuck, J.N. & Ruotolo, B.T. Curr. Opin. Chem. Biol. 17, 809–817 (2013).

    Article  CAS  Google Scholar 

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Acknowledgements

The authors thank J. Gestwicki, J. Wells, P. Arora and L. Kiessling for illuminating discussions.

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Authors and Affiliations

  1. Rachel Pricer and Steven Sturlis are at the Life Sciences Institute and the Department of Chemistry, Anna K. Mapp, University of Michigan, Ann Arbor, Michigan, USA.,

    Anna K Mapp, Rachel Pricer & Steven Sturlis

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  1. Anna K Mapp
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Correspondence to Anna K Mapp.

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Mapp, A., Pricer, R. & Sturlis, S. Targeting transcription is no longer a quixotic quest. Nat Chem Biol 11, 891–894 (2015). https://doi.org/10.1038/nchembio.1962

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