Targeting USP2 regulation of VPRBP-mediated degradation of p53 | ResearchBunny

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Abstract

Mdm2 inhibitors, while effective in reactivating p53 in pre-clinical models, show serious toxicity in clinical trials. This study identifies the USP2-VPRBP axis as a crucial regulator of p53 and PD-L1. VPRBP, a p53 repressor, is stabilized by USP2. The combination of a USP2 inhibitor and anti-PD1 antibody leads to complete tumor regression in wild-type p53 tumors, without the toxicity observed with Mdm2 inhibitors. This USP2/VPRBP targeting strategy offers a promising p53-based cancer therapy.

Publisher

Nature Communications

Published On

Apr 06, 2023

Authors

Jingjie Yi, Omid Tavana, Huan Li, Donglai Wang, Richard J. Baer, Wei Gu

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