USP14 and cancer: Additionally, the proteasome-associated DUB USP14 is also well known for suppressing substrate degradation by separating proteasome-bound polyubiquitin chains.445 USP14 works as an oncogene and is overexpressed in several cancers, which may be associated with WNT/β-catenin signaling.446,447 Moreover, USP14 is also positively correlated with tumor recurrence and poor prognosis.448,449 After chemical library screening, the inhibitor IU1 was identified to bind specifically to the activated form of USP14 and abrogate its enzymatic activity (Table 1).