Effect of BET Missense Mutations on Bromodomain Function, Inhibitor Binding and Stability.

ABSTRACT: Lysine acetylation is an important epigenetic mark regulating gene transcription and chromatin structure. Acetylated lysine residues are specifically recognized by bromodomains, small protein interaction modules that read these modification in a sequence and acetylation dependent way regulating the recruitment of transcriptional regulators and chromatin remodelling enzymes to acetylated sites in chromatin. Recent studies revealed that bromodomains are highly druggable protein interaction domains resulting in the development of a large number of bromodomain inhibitors. BET bromodomain inhibitors received a lot of attention in the oncology field resulting in the rapid translation of early BET bromodomain inhibitors into clinical studies. Here we investigated the effects of mutations present

SUBMITTER: Lori L 

PROVIDER: S-EPMC4942050 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature