Bromodomain-containing protein 2 bromodomain 2 (BRD2 BD2) (BRD2 BD2)

Bromodomain-containing protein 2 (BRD2) is a member of the Bromodomain and Extra-Terminal (BET) family of epigenetic readers, which also includes BRD3, BRD4, and BRDT (UniProt: O60885). It contains two tandem N-terminal bromodomains, BD1 and BD2, that function as readers of acetylated lysine residues on histone tails and other nuclear proteins (PubMed: 20871596). The second bromodomain (BD2) of BRD2 is specifically involved in the recruitment of transcriptional machinery to promoters and enhancers, facilitating the expression of genes critical for cell cycle progression, such as cyclin A, and inflammatory responses (PubMed: 32193360). In diseases like glioblastoma, BRD2 BD2 is essential for maintaining the mesenchymal phenotype and promoting therapy resistance (PubMed: 35410381). Small-molecule inhibitors targeting the BD2 domain, such as ABBV-744 and GSK046, are designed to competitively bind the acetyl-lysine pocket, thereby displacing BRD2 from chromatin and suppressing oncogenic or pro-inflammatory gene expression (PubMed: 31969702). These selective inhibitors are being developed to improve therapeutic windows and reduce the systemic toxicities, such as thrombocytopenia, often associated with non-selective pan-BET inhibition (PubMed: 32193360).

Other names

RING3RNF3FSHFSRG1NATO27.1.1Bromodomain-containing protein 2 (second bromodomain)BRD2-BD2

Competitive inhibition of acetyl-lysine binding in the bromodomain hydrophobic pocket, displacing the protein from chromatin and disrupting transcriptional complexes.