Acetylation of lysine residues is a posttranslational modification that plays a key role in the regulation of chromatin structure and transcription. In cancer, aberrant lysine acetylation often leads to changes in gene expression resulting in inactivation of tumour suppressor functions and the activation of pro-survival and proliferation promoting pathways. Enzymes that "write" (acetyltransferases, HATs) and "erase" (histone deacetylases, HDACs) ε-N-acetyl-lysine (Kac) marks have therefore emerged as interesting targets for the development of novel drugs for cancer treatment. Recently also acetyl-lysine reader domains have gained interest as novel targets for pharmacological intervention. The acetyl-lysine mark is specifically recognized by the bromodomain family of protein interaction modules. Bromodomains are present in diverse nuclear proteins regulating the recruitment of transcriptional regulators and chromatin modifying enzymes and proteins to acetylated chromatin as well as proteins mediating the assembly of other nuclear protein complexes. Dysfunction of bromodomain containing proteins such as chromosomal rearrangements and aberrant expression of these proteins in cancer has been tightly linked to tumourigenesis. Recently identified inhibitors that selectively target bromodomains demonstrated potent anti-tumour activity, suggesting new avenues for the development of antineoplastic drugs. In this chapter we will review the current knowledge of the role of bromodomains in tumour development and identified selective inhibitors developed to disrupt acetyl-lysine dependent protein interactions mediated by this family of transcriptional regulators. © Springer Science+Business Media New York 2014.
CITATION STYLE
Müller, S., Lingard, H., & Knapp, S. (2014). Selective inhibition of acetyl-lysine effector domains of the bromodomain family in oncology. Cancer Drug Discovery and Development, 88, 279–298. https://doi.org/10.1007/978-1-4614-8039-6_11
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