Bromodomain-containing protein 4 bromodomain 2 (BRD4 BD2)

Bromodomain-containing protein 4 (BRD4) is a key member of the Bromodomain and Extra-Terminal (BET) family of epigenetic readers, characterized by two tandem N-terminal bromodomains, BD1 and BD2 (UniProt, Wikipedia). While BD1 primarily anchors BRD4 to acetylated histones on chromatin, the second bromodomain (BD2) is specifically responsible for recruiting transcriptional co-activators and transcription factors, such as the positive transcription elongation factor b (P-TEFb) and NF-κB (PubMed, NIH). This recruitment facilitates the expression of critical oncogenes like MYC and various pro-inflammatory cytokines, making BRD4 BD2 a pivotal regulator in cancer progression, chronic inflammation, and fibrotic diseases (ACS, NIH). Dysregulation of BRD4-mediated pathways is implicated in diverse pathologies, including acute myeloid leukemia, prostate cancer, and cardiovascular conditions like vein graft failure (UniProt, ACS). Pharmacological targeting of the BD2 domain has emerged as a promising therapeutic strategy, with selective BD2 inhibitors demonstrating improved safety profiles—specifically reduced gastrointestinal and hematological toxicities—compared to pan-BET inhibitors (Nature). These inhibitors work by competitively binding to the acetyl-lysine binding pocket of BD2, thereby disrupting the assembly of transcriptional complexes at super-enhancers and promoters (ACS, Nature). Selective targeting of BRD4 BD2 is currently being explored in clinical and preclinical settings to treat conditions ranging from atherosclerosis to advanced malignancies (ClinicalTrials.gov).

Other names

BRD4CAPCDLS6FSHRG4HUNK1HUNKIMCAPBromodomain-containing protein 4

Competitive inhibition of acetyl-lysine binding to the BD2 domain, disrupting the recruitment of transcriptional co-activators like P-TEFb and suppressing the expression of target genes.