title: Bromodomain Histone Readers and Cancer.
abstract: 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.
authors.affiliation: 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.
authors.forename: Abhinav K
authors.initials: AK
authors.lastname: Jain
authors.affiliation: 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: mbarton@mdanderson.org.
authors.forename: Michelle C
authors.initials: MC
authors.lastname: Barton
mesh_terms: D000107:Acetylation; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism*; D009369:Neoplasms / Q000503:physiopathology*; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D014158:Transcription, Genetic
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D006657:Histones
keywords: acetylation; chromatin; disease; histone reader; post-translational modifications