title: Beating the odds: BETs in disease.
abstract: Bromodomains (BRDs) are evolutionarily conserved protein interaction modules that specifically recognise acetyl-lysine on histones and other proteins, facilitating roles in regulating gene transcription. BRD-containing proteins bound to chromatin loci such as enhancers are often deregulated in disease leading to aberrant expression of proinflammatory cytokines and growth-promoting genes. Recent developments targeting the bromo and extraterminal (BET) subset of BRD proteins demonstrated remarkable efficacy in murine models providing a compelling rationale for drug development and translation to the clinic. Here we summarise recent advances in our understanding of the roles of BETs in regulating gene transcription in normal and diseased tissue as well as the current status of their clinical translation.
authors.affiliation: Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7DQ, UK.
authors.forename: Chen-Yi
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7DQ, UK; Structural Genomics Consortium, Nuffield Department of Clinical Medicine, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK. Electronic address: panagis.filippakopoulos@sgc.ox.ac.uk.
authors.forename: Panagis
authors.initials: P
authors.lastname: Filippakopoulos
mesh_terms: D000818:Animals; D002868:Chromosomal Proteins, Non-Histone / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D004194:Disease; D006801:Humans; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D002868:Chromosomal Proteins, Non-Histone
keywords: BETs; cancer; inflammation; small-molecule inhibitor; transcription; viral infection