Restraining CDK1–cyclin B activation: PP2A on the cUSP(7)

Abstract

USP7 inhibitors are gaining momentum as a therapeutic strategy to stabilize p53 through their ability to induce MDM2 degradation. However, these inhibitors come with an unexpected p53-independent toxicity, via an unknown mechanism. In this issue of The EMBO Journal, Galarreta et al report how inhibition of USP7 leads to redistribution of PP2A from cytoplasm to nucleus and an increase of deleterious CDK1-dependent phosphorylation throughout the cell cycle, revealing a new regulatory mechanism for the progression of Sphase cells toward mitosis to maintain genomic integrity.