Enhancement of proteasome activity by a small-molecule inhibitor of USP14

In Alex's class we discussed ubiquitin labeling technologies which can degrade proteins. Naturally proteins are ubquitinated via the E1,E2, E3 pathway and broken down by the proteasome. The protein USP14 is in a class of ubquitin trimming enzymes that prevent degradation of a target protein. This paper describes the discovery and use of a small molecule that inhibits USP14, which results in a increase in proteasomal degradation.