BRD4 in physiology and pathology: ''BET'' on its partners

Bromodomain-containing 4 (BRD4), a member of Bromo and Extra-Terminal (BET) family, recognizes acetylated histones and is of importance in transcription, replication, and DNA repair. It also binds non-histone proteins, DNA and RNA, contributing to development, tissue growth, and various physiological processes. Additionally, BRD4 has been implicated in driving diverse diseases, ranging from cancer, viral infection, inflammation to neurological disorders. Inhibiting its functions with BET inhibitors (BETis) suppresses the progression of several types of cancer, creating an impetus for translating these chemicals to the clinic. The diverse roles of BRD4 are largely dependent on its interaction partners in different contexts. In this review we discuss the molecular mechanisms of BRD4 with its interacting partners in physiology and pathology. Current development of BETis is also summarized. Further understanding the functions of BRD4 and its partners will facilitate resolving the liabilities of present BETis and accelerate their clinical translation.

Automated summary

BRD4, a member of the BET family, plays important roles in transcription, replication, DNA repair, and various physiological processes. It is also implicated in driving diverse diseases such as cancer, viral infection, inflammation, and neurological disorders. Inhibiting BRD4 functions with BETis can suppress cancer progression, and current research is focused on the development of BET inhibitors.