Ubiquitination Screening & Profiling

Ubiquitination is a post-translational modification in which one or more ubiquitin proteins are added to a substrate protein by a stepwise reaction requiring the sequential activity of 3 enzymes: ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2), and ubiquitin ligases (E3). While originally described as the process that labels proteins for degradation by the proteasome, ubiquitination was later found to have distinct functions such as altering protein localization, modulation of protein-protein interaction, and activation or inactivation of target proteins. In addition to the highly studied proteasomal degradation pathway and autophagy, ubiquitin modifications have been linked to the regulation of other important cellular processes, including inflammation, response to stress or viral infections, DNA repair, and stem cell differentiation. Dysfunctions in the pathway are known to result in developmental, neurodegenerative, immunological and metabolic disorders, as well as cancer.

Deubiquitinating enzymes (DUBs) remove ubiquitin molecules from proteins, counteracting ubiquitination effects. Since the balance between conjugating and deconjugating systems determines the result of the various ubiquitination signals, both processes are now targets for therapeutics that either enhance or prevent ubiquitination. Notably, the ubiquitin-driven proteasomal pathway is now used to specifically target proteins for degradation using Proteolysis Targeting Chimeras (PROTACs®) as a therapeutic approach.