Bromodomain Histone Readers and Cancer
- J Mol Biol. 2017 Jun 30;429(13):2003-2010. doi: 10.1016/j.jmb.2016.11.020.
- 1. Department of Epigenetics & Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for Stem Cell & Development Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
- 2. Department of Epigenetics & Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for Stem Cell & Development Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030, USA. Electronic address: [email protected].
Lysine acetylation of histone proteins is a fundamental post-translational modification that regulates chromatin structure and plays an important role in gene transcription. Aberrant levels of histone lysine acetylation are associated with the development of several diseases. Acetyl-lysine modifications create docking sites for bromodomains, which are structurally conserved modules present in transcription-associated proteins that are termed "reader" proteins. Bromodomain-containing reader proteins are part of multiprotein complexes that regulate transcription programs, which are often associated with profound phenotypic changes. Many bromodomain-containing proteins are aberrantly expressed in diseases, as best studied in cancers, where bromodomain proteins impact the expression of oncogenes and anti-apoptotic proteins. Thus, bromodomain readers of histone acetylation have emerged as attractive targets for Cancer drug discovery, prompting immense interest in epigenetic-focused, medicinal chemistry to develop structurally guided chemical probes of bromodomains. Here, we describe bromodomain-containing proteins with defined roles in Cancer and highlight recent progress in the development of bromodomain inhibitors.