Bromodomain Histone Readers and Cancer

被引:83
作者
Jain, Abhinav K. [1 ,2 ,3 ]
Barton, Michelle C. [1 ,2 ,3 ,4 ]
机构
[1] Univ Texas MD Anderson Canc Ctr, Dept Epigenet & Mol Carcinogenesis, 1515 Holcombe Blvd,Unit 1000, Houston, TX 77030 USA
[2] Univ Texas MD Anderson Canc Ctr, Ctr Stem Cell & Dev Biol, Houston, TX 77030 USA
[3] Univ Texas MD Anderson Canc Ctr, Ctr Canc Epigenet, Houston, TX 77030 USA
[4] Univ Texas Houston, Grad Sch Biomed Sci Houston, Houston, TX 77030 USA
关键词
BET BROMODOMAINS; SELECTIVE-INHIBITION; THERAPEUTIC STRATEGY; EPIGENETIC READERS; EPIGENOME READER; PROSTATE-CANCER; DRUG DISCOVERY; PROTEIN BRD4; TARGET; MYC;
D O I
10.1016/j.jmb.2016.11.020
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (C) 2016 Elsevier Ltd. All rights reserved.
引用
收藏
页码:2003 / 2010
页数:8
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