Functions of bromodomain-containing proteins and their roles in homeostasis and cancer

Bromodomains (BRDs) are domains found in diverse proteins that recognize acetylated Lys residues, primarily on histones. Hence, BRD-containing proteins serve as readers of protein acetylation and engage in the regulation of gene expression. Recent studies have provided new insights into the physiological roles of BRD-containing proteins and their deregulation in cancer. Bromodomains (BRDs) are evolutionarily conserved protein–protein interaction modules that are found in a wide range of proteins with diverse catalytic and scaffolding functions and are present in most tissues. BRDs selectively recognize and bind to acetylated Lys residues — particularly in histones — and thereby have important roles in the regulation of gene expression. BRD-containing proteins are frequently dysregulated in cancer, they participate in gene fusions that generate diverse, frequently oncogenic proteins, and many cancer-causing mutations have been mapped to the BRDs themselves. Importantly, BRDs can be targeted by small-molecule inhibitors, which has stimulated many translational research projects that seek to attenuate the aberrant functions of BRD-containing proteins in disease.