Bromodomain-containing protein 3 (BRD3) bromodomain 1 (BD1) (BRD3-BD1)

Bromodomain-containing protein 3 (BRD3) is a member of the Bromodomain and Extra-Terminal (BET) family, which also includes BRD2, BRD4, and BRDT (UniProt: Q15059). BRD3 contains two tandem bromodomains, BD1 and BD2, that serve as epigenetic readers by recognizing and binding to acetylated lysine residues on histone tails and various transcription factors (PubMed: 24360278). Bromodomain 1 (BD1) is the N-terminal domain and plays a vital role in recruiting BRD3 to specific chromatin sites to facilitate the transcription of genes involved in cell growth and proliferation (PubMed: 21297644). In clinical contexts, BRD3 is notably involved in NUT midline carcinoma through chromosomal translocations that create the BRD3-NUT fusion protein, driving aggressive tumor growth (PubMed: 17662135). Small molecule inhibitors like JQ1 and Birabresib target the BD1 pocket to disrupt these protein-protein interactions, effectively suppressing the expression of key oncogenes like MYC (PubMed: 20946927). Current therapeutic challenges include managing systemic toxicities such as thrombocytopenia and developing inhibitors with higher selectivity for BD1 over BD2 to improve the therapeutic index (PubMed: 27108504).

Other names

BRD3 BD1Bromodomain-containing protein 3 N-terminal bromodomainRING3LORFX

Competitive inhibition of acetylated lysine binding to the bromodomain pocket, which displaces the BET protein from chromatin and leads to the downregulation of oncogenic transcription factors such as MYC (PubMed: 20946927).