Bromodomain-containing protein (BRD) (BRD)

Bromodomain-containing proteins are a family of evolutionary conserved protein modules that function as epigenetic readers by recognizing and binding to acetylated lysine residues on histone tails and other nuclear proteins (UniProt, 2023). This binding facilitates the recruitment of various molecular complexes involved in chromatin remodeling and transcriptional regulation, thereby playing a pivotal role in controlling gene expression patterns. The most prominent members belong to the Bromodomain and Extra-Terminal (BET) family, including BRD2, BRD3, and BRD4, which are frequently dysregulated in human diseases (PubMed: 24463513). In many cancers, these proteins are hijacked to drive the high-level expression of key oncogenes such as MYC and BCL2, making them high-priority therapeutic targets. Small-molecule inhibitors designed to occupy the acetyl-lysine binding pocket have demonstrated significant efficacy in preclinical models and are currently being evaluated in clinical trials for malignancies and inflammatory disorders (Nature Reviews Drug Discovery, 2014). Despite their potential, the clinical development of bromodomain inhibitors faces challenges such as dose-limiting toxicities, particularly thrombocytopenia, and the development of resistance mechanisms (PubMed: 28418235).

Other names

Bromodomain proteinsBET proteinsAcetyl-lysine readersBromodomain-containing proteins

Bromodomain inhibitors (BETis) act by competitively binding to the acetyl-lysine recognition pocket of bromodomains. This prevents the proteins from docking onto acetylated histones, thereby disrupting the assembly of transcriptional elongation complexes and suppressing the expression of downstream target genes, most notably the MYC oncogene (PubMed: 20978148, PubMed: 24463513).