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

Bromodomain-containing protein 2, bromodomain 2 (BRD2-BD2) is the second of two highly conserved N-terminal bromodomains in the BRD2 protein, a member of the Bromodomain and Extra-Terminal (BET) family [6, 18]. As an epigenetic reader, BRD2-BD2 specifically recognizes and binds to acetylated lysine residues on histone tails (notably H4K5ac and H4K12ac) and other nuclear proteins, playing a crucial role in chromatin remodeling and the regulation of gene transcription [18, 21]. BRD2 is particularly involved in the expression of genes related to the cell cycle, such as cyclin D1 and cyclin A, and the inflammatory response [13, 20]. Dysregulation of BRD2 is linked to various pathologies, including hematological malignancies, prostate cancer, glioblastoma, and chronic inflammatory diseases [5, 15, 23]. While early BET inhibitors were pan-inhibitors targeting both BD1 and BD2 across the family, recent therapeutic strategies focus on BD2-selective inhibition [1, 10]. This approach aims to achieve more specific gene modulation and reduce systemic toxicities, such as thrombocytopenia and gastrointestinal distress, which are frequently associated with pan-BET inhibition [1, 23].

Other names

RING3RNF3D6S113EFSHFSRG1NATO27.1.1Bromodomain-containing protein 2 domain 2

Competitive inhibition of the bromodomain's acetyl-lysine binding pocket, preventing the recruitment of BET proteins to chromatin and subsequent transcriptional activation of target genes [1, 10, 23].