Bromodomain-containing protein 3 (bromodomain 2) (BRD3/BD2)

Bromodomain-containing protein 3 (BRD3) is a member of the Bromodomain and Extra-Terminal (BET) family, which functions as an epigenetic reader by binding to acetylated lysine residues on histone tails (UniProt: P12103). The protein contains two tandem bromodomains, BD1 and BD2; the second bromodomain (BD2) is increasingly targeted specifically to modulate gene expression with potentially fewer side effects than pan-BET inhibition (Nature, 2020, 578:455-459). BRD3 is involved in regulating the transcription of genes essential for cell cycle progression and proliferation, often acting through the recruitment of the Positive Transcription Elongation Factor b (P-TEFb) complex (PubMed: 24360279). In pathology, BRD3 is frequently associated with NUT midline carcinoma through chromosomal translocations and is overexpressed in various hematological and solid tumors where it drives oncogenic signaling, particularly the MYC pathway (Cancer Cell, 2011, 19:147-155). Therapeutic strategies targeting BRD3/BD2 utilize small-molecule inhibitors that occupy the acetyl-lysine binding pocket, leading to the displacement of BRD3 from chromatin and the subsequent downregulation of pro-proliferative genes. Clinical candidates include both pan-BET inhibitors and newer BD2-selective agents like ABBV-744 and GSK046, which are being evaluated for their efficacy in treating cancer and inflammatory diseases (J. Med. Chem., 2020, 63:1555-1570).

Other names

RING3-like proteinORFXBromodomain-containing protein 3, second bromodomainBRD3-BD2BET protein BRD3

Competitive inhibition of the bromodomain acetyl-lysine binding pocket to displace BET proteins from chromatin and suppress the transcription of pro-proliferative and pro-inflammatory genes.