Bromodomain-containing protein 2 (BRD2) bromodomain 1 (BD1) (BRD2 BD1)

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 (UniProt P25440). It contains two highly conserved N-terminal bromodomains, BD1 and BD2, that specifically recognize and bind to acetylated lysine residues on histone tails, thereby facilitating the recruitment of transcriptional regulatory complexes to chromatin (PubMed: 24360278). BRD2 BD1 is essential for the regulation of genes involved in cell cycle progression, such as MYC and various cyclins, making it a critical node in cellular proliferation and survival (PubMed: 22464331). In oncology, BRD2 is frequently overexpressed or dysregulated, contributing to the pathogenesis of hematologic malignancies like B-cell lymphoma and various solid tumors (PubMed: 28473535). Beyond cancer, BRD2 has been identified as a key mediator of the inflammatory response and has recently been shown to regulate the expression of ACE2, the primary entry receptor for SARS-CoV-2 (PubMed: 33442033). Small-molecule inhibitors targeting the BD1 domain, such as pan-BET inhibitors or newer BD1-selective compounds, work by competitively displacing BRD2 from acetylated histones, leading to the suppression of oncogenic and pro-inflammatory gene expression (PubMed: 32523000). While therapeutic targeting of BET proteins has shown significant clinical potential, challenges remain regarding dose-limiting toxicities such as thrombocytopenia and gastrointestinal issues (PubMed: 27118431).

Other names

RING3RNF3NATD6S113EFemale sterile homeotic-related protein 1 (UniProt: P25440)

Competitive inhibition of the bromodomain-acetylated lysine interaction, resulting in the displacement of BRD2 from chromatin and subsequent suppression of downstream gene transcription (PubMed: 20871596).