Bromodomain-containing protein 2; Bromodomain-containing protein 3 (BRD2; BRD3)

Bromodomain-containing protein 2 (BRD2) and Bromodomain-containing protein 3 (BRD3) are multifunctional nuclear proteins of the BET family that contain two tandem bromodomains and an extra-terminal domain. They recognize acetylated lysine residues on histone tails, facilitating transcriptional activation by recruiting co-activators and remodeling chromatins. Both proteins play central roles in cell cycle progression, differentiation, and response to metabolic and proliferative cues. Pathologically, their dysregulation contributes to cancer, cardiac hypertrophy, inflammation, and other diseases. Therapeutic targeting is possible via BET inhibitors, which block their bromodomain-acetyllysine interactions and thus the transcription of associated disease-driving genes. While functionally somewhat redundant, BRD3 and BRD2 have unique protein partners and disease implications; for instance, BRD3 is specifically implicated in NUT midline carcinoma via gene fusion. The biological complexity and essential roles of BET proteins present both therapeutic opportunities and safety challenges.

Other names

BRD2: RING3, bromodomain containing 2BRD3: RING3-like protein, RING3L, ORFX, bromodomain containing 3

Competitive inhibition of bromodomain-acetylated lysine binding; Displacement of BRD2/BRD3 from chromatin, leading to reduced transcription of oncogenes and pathological gene programs