BET domain co-regulators in obesity, inflammation and cancer
By Anna C. Belkina, G. Denis. Nature Reviews. Cancer, 2012
696 citations recorded by the source corpus.
The bromodomain is a highly conserved motif of 110 amino acids that is bundled into four anti-parallel α-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.
Subfields: Molecular Biology, Virology
View Paper: https://www.semanticscholar.org/paper/69ecaffc8ff3f58573f07261a9e8e4932781c1f8
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In Molecular Biology
Citations in the corpus
- Hijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4. (2015, background): “The two BDs recognize and interact with acetylated lysine residues at the N-terminal tails of histones; the ET domain, which is not yet fully characterized, is largely considered to serve a scaffolding function in recruiting diverse transcriptional regulators (Belkina and Denis, 2012; Shi and Vakoc,”
- PROTAC-induced BET protein degradation as a therapy for castration-resistant prostate cancer (2016, background): “Given these emerging data, and because BET family proteins are known to have scaffolding functions whereby they interact with a variety of transcriptional regulators through their extraterminal and C-terminal domains (41, 42), we hypothesized that a BET degrader would have a more profound effect tha”
- Selective Small Molecule Induced Degradation of the BET Bromodomain Protein BRD4 (2015, neutral): “Proof-of-concept examples have been described where PROTACs were used to degrade the estrogen 20 - and androgen-receptor, 21 methionine aminopepti-dase-2, 22 as well as the aryl hydrocarbon receptor.”