Targeting bromodomian-containing protein 8 (BRD8): An advanced tool to interrogate BRD8

Epigenetic modifications play crucial roles in physiological processes, including cell differentiation, proliferation, and death. Bromodomain/Brd-containing proteins (BCPs) regulate abnormal gene expression in various diseases by recognizing the lysine-ε-N-acetylated residues (KAc) or by acting as transcriptional co-activators. Small molecule inhibitors targeting BCPs offer an attractive strategy for modulating aberrant gene expression. Besides the extensive research on the bromodomain and extra-terminal (BET) domain family proteins, the non-BET proteins have gained increasing attention. Bromodomain containing protein 8 (BRD8), a reader of KAc and co-activator of nuclear receptors (NRs), plays a key role in various cancers. This review provides a comprehensive analysis of the structure, disease-related functions, and inhibitor development of BRD8. Opportunities and challenges for future studies targeting BRD8 in disease treatment are discussed.