Assessing the Suitability of Deubiquitylases As Substrates For Targeted Protein Degradation.

ABSTRACT: Deubiquitylases (DUBs) are a family of specialized proteases that hydrolyze the isopeptide bond between a lysine and the C-terminal carboxylate of Ubiquitin. DUBs are involved in a myriad of cellular processes and many are attractive drug targets. However, it has proven extremely difficult to develop selective inhibitors due to the high degree of homology between DUB active sites. Targeted protein degradation using a proteolysis-targeting chimera (PROTAC) that recognizes the DUB in a less conserved region outside of the catalytic domain constitutes an attractive alternative strategy for selectively inhibiting a given DUB. Such ligands are unlikely to block the catalytic activity of the enzyme, raising the concern that auto-deubiqtuiylation will make DUBs inherently poor substrates for PROT

SUBMITTER: Tong J 

PROVIDER: S-EPMC12259181 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature