Bromodomain-containing protein 2 (BRD2) second bromodomain (BD2) (BRD2 (BD2))

Bromodomain-containing protein 2 (BRD2) is a member of the Bromodomain and Extra-Terminal (BET) family of epigenetic readers, which also includes BRD3, BRD4, and BRDT. It contains two highly conserved tandem bromodomains, BD1 and BD2, that recognize and bind to acetylated lysine residues on histone tails and non-histone proteins like STAT3. This binding facilitates the recruitment of transcriptional machinery, such as RNA polymerase II and P-TEFb, to regulate genes essential for cell cycle progression (e.g., Cyclin A), inflammatory responses, and adipogenesis. BRD2 is implicated in several diseases; its overexpression is linked to hematological malignancies like B-cell lymphoma and solid tumors such as prostate cancer and glioblastoma, while its role in inflammation involves the differentiation of Th17 cells. Therapeutic interest has shifted toward targeting the second bromodomain (BD2) specifically, as BD2-selective inhibitors like ABBV-744 demonstrate potent anti-proliferative and anti-inflammatory effects with reduced dose-limiting toxicities, such as thrombocytopenia and gastrointestinal distress, compared to non-selective pan-BET inhibitors.

Other names

RING3RNF3NATD6S113EFSHFSRG1O27.1.1Bromodomain-containing protein 2

Competitive inhibition of the bromodomain (specifically the second bromodomain, BD2) binding to acetylated lysine residues on histones, which displaces the protein from chromatin and prevents the recruitment of transcriptional machinery, leading to the downregulation of oncogenic and pro-inflammatory genes.