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

Bromodomain-containing protein 2 (BRD2) is a member of the Bromodomain and Extra-Terminal (BET) family, which plays a critical role in epigenetic signaling by reading acetylated lysine residues on histone tails (UniProt P25440). The second bromodomain (BD2) of BRD2 is one of two highly conserved amino-terminal domains that facilitate the recruitment of transcription factors and chromatin-remodeling complexes to specific genomic loci (PubMed: 24360278). BRD2 is essential for cell cycle progression, particularly the G1 to S phase transition, and is a key regulator of inflammatory gene expression (PubMed: 21248751). In various cancers, including leukemias and lymphomas, BRD2 is often dysregulated, leading to the constitutive activation of oncogenes like MYC. Therapeutic targeting of the BRD2 BD2 domain, often through small-molecule inhibitors, aims to disrupt these protein-protein interactions to suppress oncogenic signaling and inflammatory responses (PubMed: 32193340). While pan-BET inhibitors target both BD1 and BD2 across the family, recent drug development has focused on BD2-selective inhibitors to potentially improve the safety profile and therapeutic index by reducing systemic toxicities like thrombocytopenia (PubMed: 32193340).

Other names

RING3RNF3D6S113EBromodomain-containing protein 2Female sterile homeotic-related gene 1

Competitive inhibition of the bromodomain binding pocket, preventing the recognition of acetylated lysine residues on histones and subsequent recruitment of transcriptional complexes.