Bromodomain-containing protein 2 (BRD2) (BRD2)

Bromodomain-containing protein 2 (BRD2) is a key member of the Bromodomain and Extra-Terminal (BET) family of epigenetic reader proteins (UniProt P25440). It possesses two conserved N-terminal bromodomains (BD1 and BD2) that recognize and bind to acetylated lysine residues on histone tails, facilitating the recruitment of transcriptional machinery to chromatin (NCBI Gene 6046). BRD2 plays a critical role in regulating the expression of genes essential for cell cycle progression, particularly during the G1/S transition, and is a major mediator of the inflammatory response (PMID: 20971844). In various cancers, BRD2 is often associated with the upregulation of oncogenes like MYC, making it a high-priority target for therapeutic intervention (PMID: 24121015). Small-molecule BET inhibitors, which competitively bind to the bromodomains of BRD2, have shown promise in preclinical and clinical studies for treating hematological malignancies, solid tumors, and inflammatory diseases (ClinicalTrials.gov). Beyond oncology, BRD2 is also implicated in metabolic regulation and viral replication, including acting as a co-factor for SARS-CoV-2 entry (PMID: 32405101). These inhibitors work by displacing BRD2 from chromatin, thereby suppressing the transcription of downstream pathogenic genes. Despite their potential, therapeutic use is often limited by dose-dependent toxicities such as thrombocytopenia and gastrointestinal distress.

Other names

RING3RNF3NATD6S113EFemale sterile homeotic-related protein 1

Competitive inhibition of bromodomain binding to acetylated lysine residues on histones, resulting in the displacement of BET proteins from chromatin and the subsequent suppression of target gene transcription, such as MYC.