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

Marilynn Chow-Castro; Shandee D. Dixon; Joshua C. Saldivar

doi:10.15252/embj.2021108486

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

Marilynn Chow-Castro, Shandee D. Dixon, Joshua C. Saldivar

Knight Cancer Institute

Research output: Contribution to journal › Comment/debate › peer-review

1 Scopus citations

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 re-distribution 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 S-phase cells toward mitosis to maintain genomic integrity.

Original language	English (US)
Article number	e108486
Journal	EMBO Journal
Volume	40
Issue number	11
DOIs	https://doi.org/10.15252/embj.2021108486
State	Published - Jun 1 2021

ASJC Scopus subject areas

Neuroscience(all)
Molecular Biology
Biochemistry, Genetics and Molecular Biology(all)
Immunology and Microbiology(all)

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title = "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 re-distribution 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 S-phase cells toward mitosis to maintain genomic integrity.",

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T2 - PP2A on the cUSP(7)

AU - Chow-Castro, Marilynn

AU - Dixon, Shandee D.

AU - Saldivar, Joshua C.

PY - 2021/6/1

Y1 - 2021/6/1

N2 - 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 re-distribution 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 S-phase cells toward mitosis to maintain genomic integrity.

AB - 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 re-distribution 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 S-phase cells toward mitosis to maintain genomic integrity.

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JO - EMBO Journal

JF - EMBO Journal

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M1 - e108486

ER -

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

Abstract

ASJC Scopus subject areas

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