Designer polyQ fusion proteins sequester USP7/HDM2 for modulating P53 functionality.

ABSTRACT: Overexpression of USP7 and HDM2 inactivates P53 signaling in tumor cells and facilitates their progression, but suppression of these targets by conventional strategies to reactivate P53 function remains a challenge. We applied polyQ sequences and target-interacting peptides to engineer polyQ fusion proteins that specifically sequester the targets, hence depleting their availabilities and modulating the P53 functionality. We have revealed that the designer fusion Atx7_93Q-N172-IRF (IRF sequence: SPGEGPSGTG) sequesters USP7 and/or HDM2 into aggregates and thereby increases the P53 level, but it depends on the IRF repeats fused, suggesting that depletion of the USP7 availability plays a dual role in controlling P53 stability. Direct sequestration of HDM2 by Atx7_93Q-N172-P

SUBMITTER: Zhang XL 

PROVIDER: S-EPMC11914518 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature