Targeted degradation of USP7 in solid cancer cells reveals distinct effects of deubiquitinase degraders and inhibitors - PubMed
2 hours ago
- #PROTAC
- #USP7
- #Deubiquitinase
- The study uses a chemical biology approach to compare inhibition versus degradation of the deubiquitinase USP7 in melanoma and pancreatic cancer cells.
- Potent USP7 PROTACs (degraders) were identified and characterized, showing that degradation modulates both shared and distinct protein sets across cancers without affecting cell growth.
- Prolonged inhibitor treatment induced USP7-independent proteomic and metabolic dysregulation, revealing caveats for using hydroxypiperidine-based USP7 inhibitors.
- The work provides a chemical toolbox to distinguish on-target phenotypes, emphasizing the increased specificity of PROTAC-mediated degradation and its potential to elucidate cell-line specific DUB functions.