DUBs and disease: activity assays for inhibitor development.

Deubiquitinating enzymes (DUBs) cleave ubiquitin from substrate proteins and so influence the biochemical properties of these proteins, such as their half-life, by a reduction in proteasomal degradation. Several DUBs have been demonstrated to deubiquitinate oncogenic proteins and tumor suppressors, and their activities have been implicated in numerous processes related to disease, including cancer and neurodegeneration. The importance of various DUBs is well established, but the understanding of both their selectivity and reactivity in the ubiquitin-proteasome system is comparatively poor. In this review, the published methods that are available to study DUB action in vitro and their application in finding inhibitors are discussed.