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

Bromodomain-containing protein 3 (BRD3) is a member of the Bromodomain and Extra-Terminal (BET) family of epigenetic readers, which also includes BRD2, BRD4, and BRDT (UniProt Q15059). The BRD3-BD2 target specifically refers to the second of the two tandem bromodomains found in the BRD3 protein. These domains function by recognizing and binding to acetylated lysine residues on histone tails, thereby recruiting transcriptional machinery to specific chromatin sites to regulate gene expression (PubMed: 24360279). BRD3 plays a significant role in the regulation of genes associated with cell proliferation and the inflammatory response. Dysregulation of BRD3 is implicated in several pathologies, most notably in NUT midline carcinoma where it can form oncogenic fusion proteins, and in various hematological malignancies (PubMed: 17662135). Therapeutic strategies targeting the BD2 domain, such as those using Apabetalone or ABBV-744, are currently being explored to improve the safety profile of BET inhibitors (PubMed: 32433815). BD2-selective compounds may offer a wider therapeutic window compared to pan-BET inhibitors by reducing common side effects like thrombocytopenia and gastrointestinal distress (PubMed: 32134255).

Other names

Bromodomain-containing protein 3RING3-like proteinORFXBromodomain 2 of BRD3

Competitive inhibition of acetyl-lysine binding to the bromodomain, preventing the recruitment of transcriptional machinery to chromatin.