Bromodomain-containing protein 2 (BRD2), bromodomain 1 (BRD2-BD1)

Bromodomain-containing protein 2 (BRD2) is a member of the Bromodomain and Extra-Terminal (BET) family, serving as an epigenetic reader that recognizes acetylated lysine residues on histone tails (UniProt P25440). The first bromodomain (BD1) is located at the N-terminus and is essential for the protein's association with chromatin, where it facilitates the assembly of transcriptional complexes (PubMed: 20871596). BRD2-BD1 plays a pivotal role in regulating the expression of genes involved in the cell cycle, such as cyclins, and mediators of the inflammatory response (PubMed: 24855250). In many cancers, BRD2 is overexpressed or recruited to super-enhancers, driving the transcription of potent oncogenes like MYC (PubMed: 24120135). Small-molecule inhibitors targeting BRD2-BD1 displace the protein from chromatin, thereby suppressing the pathological gene expression programs associated with malignancy and chronic inflammation (PubMed: 22460902). Current drug development efforts focus on both pan-BET inhibitors and domain-selective molecules to optimize efficacy and minimize systemic toxicities like thrombocytopenia (PubMed: 28432110).

Other names

RING3RNF3D6S45Female sterile homeotic-related protein 1Bromodomain-containing protein 2

Competitive inhibition of acetylated lysine binding to the bromodomain pocket, preventing the recruitment of transcriptional machinery to chromatin.