Bromodomain-containing proteins BRD2, BRD3, BRD4 (BRD2, BRD3, BRD4)

BRD2, BRD3, and BRD4 encode nuclear proteins of the BET family characterized by two tandem bromodomains and an Extra-Terminal (ET) domain. These domains recognize acetylated lysine residues on histones and non-histone proteins, functioning as epigenetic readers that regulate transcription, chromatin structure, cell cycle progression, and inflammatory responses. BRD4, the best-characterized member, additionally possesses kinase activity toward CDK9 and RNA polymerase II, acting as a pause–release factor that promotes transcriptional elongation by RNA polymerase II. Aberrant BET protein function drives pathogenesis in cancers (notably through fusion proteins such as BRD3-NUT or BRD4-NUT in NUT midline carcinoma), inflammation, metabolic syndromes, and viral infections. Small molecule inhibitors of BET proteins are in preclinical and clinical development with potential applications in oncology and immunology, but broad effects and toxicity remain therapeutic challenges.

Other names

RING3RING3-like protein (RING3L)ORFX

Competitive inhibition of bromodomains, preventing binding to acetylated histone lysine residues. Displacement of BRD2, BRD3, and BRD4 from chromatin. Downregulation of key oncogenes (e.g., c-MYC) and suppressing transcription of genes involved in proliferation and inflammation.