Functions of bromodomain-containing proteins and their roles in homeostasis and cancer

被引:420
作者
Fujisawa, Takao [1 ,2 ]
Filippakopoulos, Panagis [1 ,2 ]
机构
[1] Ludwig Inst Canc Res, Old Rd Campus Res Bldg,Roosevelt Dr, Oxford OX3 7DQ, England
[2] Struct Genom Consortium, Old Rd Campus Res Bldg,Roosevelt Dr, Oxford OX3 7DQ, England
基金
英国惠康基金; 巴西圣保罗研究基金会; 加拿大创新基金会;
关键词
CHROMATIN-REMODELING COMPLEX; ACETYL-LYSINE RECOGNITION; PHD FINGER-BROMODOMAIN; NF-KAPPA-B; SOMATIC MUTATIONS; STRUCTURAL BASIS; DNA-DAMAGE; TRANSCRIPTIONAL ELONGATION; EMBRYONIC-DEVELOPMENT; HISTONE DEACETYLASES;
D O I
10.1038/nrm.2016.143
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Bromodomains (BRDs) are evolutionarily conserved protein-protein interaction modules that are found in a wide range of proteins with diverse catalytic and scaffolding functions and are present in most tissues. BRDs selectively recognize and bind to acetylated Lys residues - particularly in histones - and thereby have important roles in the regulation of gene expression. BRD-containing proteins are frequently dysregulated in cancer, they participate in gene fusions that generate diverse, frequently oncogenic proteins, and many cancer-causing mutations have been mapped to the BRDs themselves. Importantly, BRDs can be targeted by small-molecule inhibitors, which has stimulated many translational research projects that seek to attenuate the aberrant functions of BRD-containing proteins in disease.
引用
收藏
页码:246 / 262
页数:17
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