Sculpting the proteome with small molecules

October 17th, 2014 by Randall W King

Nature Chemical Biology 10, 870 (2014). doi:10.1038/nchembio.1671

Authors: Randall W King & Daniel Finley

The ubiquitin-proteasome system (UPS) pervades the biology of eukaryotes. Because it depends on the activity of hundreds of different enzymes and protein-protein interactions, the UPS provides many opportunities for selective modulation of the pathway with small molecules. Here we discuss the principles that underlie the development of effective inhibitors or activators of the pathway. We emphasize insights from structural analysis and describe strategies for evaluating the selectivity of compounds.