The deubiquitinase inhibitor WP1130 drives nuclear aggregation and reactivation of mutant p53 for selective cancer cell targeting.

ABSTRACT: Mutations in the TP53 gene may lead to the loss of its tumor suppressor function and the acquisition of oncogenic properties. The enhanced stability of mutant p53 (mutp53) is one of the pivotal factors for its oncogenic functions, rendering proteins implicated in mutp53 stabilization as promising targets for therapeutic intervention. Although deubiquitinases (DUBs) are commonly deregulated in various cancers, their specific impact on mutp53 stabilization remains largely unexplored. In this study, we demonstrated the involvement of DUBs-USP5 and USP9X in-enhancing mutp53 stability while revealing the effects of DUB inhibitor WP1130 in selectively destabilizing different p53 mutants in cancer cells of various origins. Mechanistically, WP1130 induced mutp53 ubiquitination and nuclear aggregat

SUBMITTER: Oak S 

PROVIDER: S-EPMC12138167 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature