Putting proteomics on target: activity-based profiling of ubiquitin and ubiquitin-like processing enzymes.
Modification of proteins with ubiquitin (Ub) and Ub-like modifiers (Ubls) plays a fundamental role in cell biology. As a consequence, proteomics-based efforts were developed to characterize proteins that are modified by Ub or Ubls. A more focused functional proteomics strategy relies on active-site probes based on the Ub/Ubl scaffold, which specifically targets Ub/Ubl-processing enzymes. Activity-based profiling with such tools led to the identification of novel gene products with Ub/Ubl-processing activity and uncovered novel control mechanisms regulating their activity. This review discusses recent advances in chemistry-based functional proteomics applications, and how this information can provide a framework for drug development against Ub/Ubl-processing enzymes.
Kessler
Benedikt M
BM
Nuffield Department of Clinical Medicine, University of Oxford, Oxford, OX3 7BN, UK. bmk@ccmp.ox.ac.uk
D000818:Animals; D020134:Catalytic Domain; D006801:Humans; D011485:Protein Binding; D040901:Proteomics / Q000379:methods*; D013379:Substrate Specificity; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism*; D014452:Ubiquitins / Q000378:metabolism*
D014452:Ubiquitins; D043743:Ubiquitin-Protein Ligase Complexes