Advancing our understanding of ubiquitination using the Ub-Toolkit
2017
Witting, Katharina F. | Mulder, Monique P.C. | Ovaa, Huib
Post-translational protein modification by ubiquitin (Ub) and ubiquitin-like modifiers (Ubl) is orchestrated by the sequential action of ubiquitin activating, conjugating, and ligating enzymes to regulate a vast array of fundamental biological processes. Unsurprisingly, the dysregulation of the intricate interplay between ubiquitination and deubiquitination gives rise to numerous pathologies, most notably cancer and neurodegenerative diseases. While activity-based probes (ABPs) and assay reagents have been extensively developed and applied for deubiquitinating enzymes (DUBs), similar tools for the ubiquitin cascade have only recently emerged. Given the recent efforts to develop inhibitors for the ubiquitin system, the urgency for developing ABPs and assay reagents is imminent. In this light, we comprehensively discuss the currently available ABPs with a focus on the newly developed reagents targeting the ubiquitin cascade, while illustrating their potential applications.
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