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

Bromodomain-containing protein 3 (BRD3) is a member of the bromodomain and extra-terminal (BET) family of epigenetic readers, characterized by two tandem N-terminal bromodomains, BD1 and BD2 [1.2.3, 1.4.4]. The second bromodomain (BD2) specifically recognizes and binds to acetylated lysine residues on histone tails and non-histone proteins, such as GATA1, to facilitate the recruitment of transcriptional machinery and regulate gene expression [1.1.2, 1.2.2, 1.4.2]. BRD3 BD2 plays a critical role in various cellular processes, including cell cycle progression, apoptosis, and the inflammatory response [1.2.2, 1.2.5]. In disease contexts, BRD3 is implicated in several cancers, such as NUT midline carcinoma and prostate cancer, as well as chronic inflammatory conditions like rheumatoid arthritis and cardiovascular diseases [1.2.1, 1.2.2, 1.2.5]. Small molecule inhibitors targeting the BD2 domain, such as ABBV-744 and Apabetalone, aim to disrupt these interactions to modulate the expression of oncogenic or pro-inflammatory genes [1.3.1, 1.4.2]. Selective inhibition of BD2 is often pursued to improve the therapeutic window by reducing dose-limiting toxicities, such as thrombocytopenia and gastrointestinal issues, which are typically associated with pan-BET or BD1-selective inhibition [1.3.1, 1.3.4].

Other names

RING3-like protein bromodomain 2RING3L BD2ORFX BD2Bromodomain-containing protein 3 second bromodomainBRD3-BD2

Competitive inhibition of the bromodomain-acetyl lysine interaction, leading to the displacement of the BET protein from chromatin and subsequent downregulation of target gene transcription.