Bromodomain-containing protein 3, bromodomain 1 (BRD3/BD1)

Bromodomain-containing protein 3 (BRD3) is a member of the Bromodomain and Extra-Terminal (BET) family of epigenetic readers, which play a critical role in regulating gene expression by binding to acetylated lysine residues on histone tails (UniProt P78527). BRD3 contains two highly conserved N-terminal bromodomains, BD1 and BD2, which facilitate the recruitment of transcriptional machinery to specific chromatin sites (PMID: 24360279). In many cancers, BRD3 is involved in the dysregulation of oncogenic drivers, most notably through the formation of the BRD3-NUT fusion protein in NUT midline carcinoma, a highly aggressive malignancy (PMID: 17634284). Beyond its role in cancer, BRD3 is implicated in inflammatory responses and the regulation of hematopoiesis (PMID: 21909115). Therapeutic strategies targeting BRD3/BD1 primarily involve small-molecule inhibitors that competitively bind to the acetyl-lysine pocket, thereby displacing the protein from chromatin and suppressing the transcription of downstream targets like MYC (PMID: 20871596). While pan-BET inhibitors have shown clinical activity, research is increasingly focused on domain-selective inhibitors, such as those targeting BD1, to improve the therapeutic index and reduce systemic toxicities like thrombocytopenia (PMID: 32188940).

Other names

RING3LORFXBromodomain-containing protein 3RING3-like protein

Competitive inhibition of the acetyl-lysine binding pocket within the first bromodomain (BD1), preventing the protein from binding to acetylated histones and recruiting transcriptional co-activators to oncogenic promoters.