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

Bromodomain-containing protein 3 (BRD3) is a member of the Bromodomain and Extra-Terminal (BET) family, which functions as an epigenetic reader by binding to acetylated lysine residues on histone tails (UniProt Q15059). It contains two highly conserved N-terminal bromodomains, BD1 and BD2, which are essential for its recruitment to chromatin and subsequent regulation of gene transcription (PubMed: 24703830). BRD3 is particularly significant in the context of NUT midline carcinoma, where it can form oncogenic fusion proteins with the NUT (Nuclear Protein in Testis) gene, driving aggressive tumor growth (NCBI Gene: 8019). Beyond fusions, BRD3 supports the expression of key oncogenes like MYC in various hematologic and solid malignancies (PubMed: 27153392). Therapeutic targeting of the second bromodomain (BD2) has emerged as a strategy to achieve more specific transcriptional modulation with potentially fewer side effects than pan-BET inhibition (PubMed: 32139344). Small molecule inhibitors, such as ABBV-744, specifically target the BD2 domain to disrupt the assembly of transcriptional complexes at enhancers and promoters (PubMed: 32139344). While effective in preclinical models, clinical use of BET inhibitors is often limited by toxicities such as thrombocytopenia and gastrointestinal distress (PubMed: 28418267).

Other names

Bromodomain-containing protein 3BRD3RING3-like proteinORFXRING3L

Competitive inhibition of the binding of bromodomains to acetylated lysine residues on histone tails, thereby preventing the recruitment of transcriptional regulatory complexes to chromatin.