BET domain co-regulators in obesity, inflammation and cancer

被引：582

作者：

Belkina, Anna C. ^{[1
]}

Denis, Gerald V. ^{[1
]}

机构：

[1] Boston Univ, Dept Med & Pharmacol, Canc Res Ctr, Nutr Obes Res Ctr,Sch Med, Boston, MA 02118 USA

来源：

NATURE REVIEWS CANCER | 2012年 / 12卷 / 07期

基金：

美国国家卫生研究院;

关键词：

BROMODOMAIN PROTEIN BRD4; PAPILLOMAVIRUS E2 PROTEIN; FRAGMENT-BASED DISCOVERY; LATENT NUCLEAR ANTIGEN; ACUTE MYELOID-LEUKEMIA; CELL-CYCLE; GENE-EXPRESSION; TRANSCRIPTIONAL ACTIVATION; METABOLICALLY HEALTHY; HISTONE DEACETYLASE;

D O I：

10.1038/nrc3256

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The bromodomain is a highly conserved motif of 110 amino acids that is bundled into four anti-parallel alpha-helices and found in proteins that interact with chromatin, such as transcription factors, histone acetylases and nucleosome remodelling complexes. Bromodomain proteins are chromatin 'readers'; they recruit chromatin-regulating enzymes, including 'writers' and 'erasers' of histone modification, to target promoters and to regulate gene expression. Conventional wisdom held that complexes involved in chromatin dynamics are not 'druggable' targets. However, small molecules that inhibit bromodomain and extraterminal (BET) proteins have been described. We examine these developments and discuss the implications for small molecule epigenetic targeting of chromatin networks in cancer.

引用

页码：465 / 477

页数：13

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