Bromodomain-containing protein 4, Bromodomain 2 (BRD4 BD2)

Bromodomain-containing protein 4 (BRD4) is a key epigenetic reader belonging to the Bromodomain and Extra-Terminal (BET) family, featuring two conserved N-terminal bromodomains, BD1 and BD2 (UniProt: P21709). BRD4 BD2 specifically refers to the second bromodomain, which binds to acetylated lysine residues on histones and transcription factors to regulate gene expression, particularly during the elongation phase of transcription (PubMed: 32132175). In oncology, BRD4 BD2 is frequently associated with the over-expression of the MYC oncogene and the maintenance of super-enhancer-driven transcriptional programs in various malignancies, including acute myeloid leukemia and prostate cancer (PubMed: 32251035). Beyond cancer, BD2 plays a significant role in mediating inflammatory responses and cardiovascular pathologies, such as atherosclerosis and heart failure, by controlling the expression of pro-inflammatory cytokines (PubMed: 28434944). Therapeutic targeting of BD2 has emerged as a strategy to improve the therapeutic window of BET inhibitors; selective BD2 inhibitors like ABBV-744 have shown reduced systemic toxicities, such as thrombocytopenia, compared to pan-BET inhibitors (PubMed: 32251035). Clinical candidates like Apabetalone (RVX-208) specifically target BD2 to treat cardiovascular and metabolic diseases by modulating lipid metabolism and inflammatory pathways (PubMed: 24509435).

Other names

BRD4-BD2Bromodomain 2 of BRD4MCAPHUNK1Chromosome 19 open reading frame 9

Competitive inhibition of the acetyl-lysine binding pocket within the second bromodomain (BD2) of BRD4, which prevents the protein from docking onto acetylated histones and recruiting the Positive Transcription Elongation Factor b (p-TEFb) complex, thereby suppressing the transcription of pro-growth and pro-inflammatory genes (PubMed: 32251035).