The Mechanisms behind the Therapeutic Activity of BET Bromodomain Inhibition

Shi, J., Vakoc, C. R. (June 2014) The Mechanisms behind the Therapeutic Activity of BET Bromodomain Inhibition. Molecular Cell, 54 (5). pp. 728-736. ISSN 1097-2765

URL: http://www.ncbi.nlm.nih.gov/pubmed/24905006
DOI: 10.1016/j.molcel.2014.05.016

Abstract

The bromodomain and extraterminal (BET) protein Brd4 recruits transcriptional regulatory complexes to acetylated chromatin. While Brd4 is considered to be a general transcriptional regulator, pharmacological inhibition of BET proteins shows therapeutic activity in a variety of different pathologies, particularly in models of cancer and inflammation. Such effects have been attributed to a specific set of downstream target genes whose expression is disproportionately sensitive to pharmacological targeting of BET proteins. Emerging evidence links the transcriptional consequences of BET inhibition to the association of Brd4 with enhancer elements, which tend to be involved in lineage-specific gene regulation. Furthermore, Brd4 engages in direct regulatory interactions with several DNA-binding transcription factors to influence their disease-relevant functions. Here we review the current understanding of molecular mechanisms that underlie the promising therapeutic effects of BET bromodomain inhibition.

Item Type: Paper
Subjects: diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > bromodomain and extraterminal protein
diseases & disorders > cancer > drugs and therapies
CSHL Authors:
Communities: CSHL labs > Vakoc lab
Depositing User: Matt Covey
Date: 5 June 2014
Date Deposited: 13 Jun 2014 15:06
Last Modified: 13 Jun 2014 15:06
Related URLs:
URI: http://repository.cshl.edu/id/eprint/30305

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