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

被引:430
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
巴西圣保罗研究基金会; 英国惠康基金; 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
相关论文
共 188 条
[1]   Recruitment of TIF1γ to Chromatin via Its PHD Finger-Bromodomain Activates Its Ubiquitin Ligase and Transcriptional Repressor Activities [J].
Agricola, Eleonora ;
Randall, Rebecca A. ;
Gaarenstroom, Tessa ;
Dupont, Sirio ;
Hill, Caroline S. .
MOLECULAR CELL, 2011, 43 (01) :85-96
[2]   The oncogenic BRD4-NUT chromatin regulator drives aberrant transcription within large topological domains [J].
Alekseyenko, Artyom A. ;
Walsh, Erica M. ;
Wang, Xin ;
Grayson, Adlai R. ;
Hsi, Peter T. ;
Kharchenko, Peter V. ;
Kuroda, Mitzi I. ;
French, Christopher A. .
GENES & DEVELOPMENT, 2015, 29 (14) :1507-1523
[3]   Large-Scale Computational Screening Identifies First in Class Multitarget Inhibitor of EGFR Kinase and BRD4 [J].
Allen, Bryce K. ;
Mehta, Saurabh ;
Ember, Stewart W. J. ;
Schonbrunn, Ernst ;
Ayad, Nagi ;
Schuerer, Stephan C. .
SCIENTIFIC REPORTS, 2015, 5
[4]   BRD4 Short Isoform Interacts with RRP1B, SIPA1 and Components of the LINC Complex at the Inner Face of the Nuclear Membrane [J].
Alsarraj, Jude ;
Faraji, Farhoud ;
Geiger, Thomas R. ;
Mattaini, Katherine R. ;
Williams, Mia ;
Wu, Josephine ;
Ha, Ngoc-Han ;
Merlino, Tyler ;
Walker, Renard C. ;
Bosley, Allen D. ;
Xiao, Zhen ;
Andresson, Thorkell ;
Esposito, Dominic ;
Smithers, Nicholas ;
Lugo, Dave ;
Prinjha, Rab ;
Day, Anup ;
Crawford, Nigel P. S. ;
Ozato, Keiko ;
Gardner, Kevin ;
Hunter, Kent W. .
PLOS ONE, 2013, 8 (11)
[5]   NuA4-dependent Acetylation of Nucleosomal Histones H4 and H2A Directly Stimulates Incorporation of H2A.Z by the SWR1 Complex [J].
Altaf, Mohammed ;
Auger, Andreanne ;
Monnet-Saksouk, Julie ;
Brodeur, Joelle ;
Piquet, Sandra ;
Cramet, Myriam ;
Bouchard, Nathalie ;
Lacoste, Nicolas ;
Utley, Rhea T. ;
Gaudreau, Luc ;
Cote, Jacques .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (21) :15966-15977
[6]   NUT Carcinoma of the Sublingual Gland [J].
Andreasen S. ;
French C.A. ;
Josiassen M. ;
Hahn C.H. ;
Kiss K. .
Head and Neck Pathology, 2016, 10 (3) :362-366
[7]   The Taf14 YEATS domain is a reader of histone crotonylation [J].
Andrews, Forest H. ;
Shinsky, Stephen A. ;
Shanle, Erin K. ;
Bridgers, Joseph B. ;
Gest, Anneliese ;
Tsun, Ian K. ;
Krajewski, Krzysztof ;
Shi, Xiaobing ;
Strahl, Brian D. ;
Kutateladze, Tatiana G. .
NATURE CHEMICAL BIOLOGY, 2016, 12 (06) :396-U33
[8]   Detection of Redundant Fusion Transcripts as Biomarkers or Disease- Specific Therapeutic Targets in Breast Cancer [J].
Asmann, Yan W. ;
Necela, Brian M. ;
Kalari, Krishna R. ;
Hossain, Asif ;
Baker, Tiffany R. ;
Carr, Jennifer M. ;
Davis, Caroline ;
Getz, Julie E. ;
Hostetter, Galen ;
Li, Xing ;
McLaughlin, Sarah A. ;
Radisky, Derek C. ;
Schroth, Gary P. ;
Cunliffe, Heather E. ;
Perez, Edith A. ;
Thompson, E. Aubrey .
CANCER RESEARCH, 2012, 72 (08) :1921-1928
[9]   Regulation of chromatin by histone modifications [J].
Bannister, Andrew J. ;
Kouzarides, Tony .
CELL RESEARCH, 2011, 21 (03) :381-395
[10]   CECR2, a protein involved in neurulation, forms a novel chromatin remodeling complex with SNF2L [J].
Banting, GS ;
Barak, O ;
Ames, TM ;
Burnham, AC ;
Kardel, MD ;
Cooch, NS ;
Davidson, CE ;
Godbout, R ;
McDermid, HE ;
Shiekhattar, R .
HUMAN MOLECULAR GENETICS, 2005, 14 (04) :513-524