UbiScout™

Protein ubiquitination is a critical aspect of cellular protein regulation in which proteins are post-translationally modified to attach a ubiquitin (Ub) moiety. This addition typically targets the modified protein for proteasomal degradation, a phenomenon which has been harnessed for therapeutic purposes by modalities such as PROTACs and molecular glue degrader (MGDs). UbiScout™ is a global ubiquitinome profiling technology that quantitatively analyzes ubiquitination sites across the proteome. In addition to characterizing fundamental biological processes, these data can reveal PROTAC/MGD selectivity and provide structural and mechanistic insights into ternary complex formation of targets and their respective E3 ligase complexes. Our UbiScout™ workflow can incorporate proteasome inhibition strategies to prevent the degradation of ubiquitinated proteins, thereby enhancing ubiquitin signal. UbiScout™ is a valuable tool for the profiling of compound-induced protein ubiquitination, with particular utility in the development of targeted protein degradation modalities. This assay is well-suited as a follow-up to proteome-wide protein degradation profiling (ProteomeScout™), and ubiquitinome profiling data can be integrated with protein turnover data (TurnoverScout™, Protein Turnover Atlas™) to obtain comprehensive insights into compound activity.