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Chromatin targeting

A BET inhibitor workaround

Nature Chemical Biology volume 12, pages 469–470 (2016)Cite this article

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A phenotypic cell-based screen identifies an inhibitor of BET bromodomain transcriptional activity via inhibition of the alternative bromodomain-containing protein TAF1.

The bromodomain structural motif is found in proteins that bind to acetylated lysine residues, which are predominantly present on histones. There are 46 proteins in the human genome known to contain at least one bromodomain motif; these proteins impact chromatin architecture, and many regulate transcriptional activity1. Therapeutic targeting of bromodomain proteins is of increasing interest, though to date it has been largely focused on inhibition of the BET bromodomain family member BRD4, as preclinical evidence has shown that this controls the expression of well-known oncogenic transcription factors such as MYC and FOSL1. Sdelci et al.2 now report a new screen that has resulted in the identification of a compound that modulates BRD4-mediated transcription through inhibition of an alternative bromodomain-containing protein, TAF1.

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Figure 1: Modulation of BET bromodomain functional activity.

References

  1. Filippakopoulos, P. & Knapp, S. Nat. Rev. Drug Discov. 13, 337–356 (2014).

    Article  CAS  Google Scholar 

  2. Sdelci, S. et al. Nat. Chem. Biol. 12, 504–510 (2016).

    Article  CAS  Google Scholar 

  3. Lovén, J. et al. Cell 153, 320–334 (2013).

    Article  Google Scholar 

  4. Liu, X., Vorontchikhina, M., Wang, Y.L., Faiola, F. & Martinez, E. Mol. Cell. Biol. 28, 108–121 (2008).

    Article  Google Scholar 

  5. Li, H.-H., Li, A.G., Sheppard, H.M. & Liu, X. Mol. Cell 13, 867–878 (2004).

    Article  CAS  Google Scholar 

  6. Belkina, A.C. & Denis, G.V. Nat. Rev. Cancer 12, 465–477 (2012).

    Article  CAS  Google Scholar 

  7. Vidler, L.R., Brown, N., Knapp, S. & Hoelder, S. J. Med. Chem. 55, 7346–7359 (2012).

    Article  CAS  Google Scholar 

  8. Tran, T.A. et al. ACS Chem. Biol. 9, 2603–2611 (2014).

    Article  CAS  Google Scholar 

  9. Wang, L. et al. Nat. Commun. 4, 2035 (2013).

    Article  Google Scholar 

  10. Zengerle, M., Chan, K.H. & Ciulli, A. ACS Chem. Biol. 10, 1770–1777 (2015).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Christopher J. Burns is in The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.,

    Christopher J Burns

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  1. Christopher J Burns
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Correspondence to Christopher J Burns.

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The author declares no competing financial interests.

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Burns, C. A BET inhibitor workaround. Nat Chem Biol 12, 469–470 (2016). https://doi.org/10.1038/nchembio.2107

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