Journal ArticleDOI
Restraining CDK1–cyclin B activation: PP2A on the cUSP(7)
TLDR
Galarreta et al. as mentioned in this paper showed that USP7 inhibition 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.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.read more
Citations
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Journal ArticleDOI
TRIM29 regulates the SETBP1/SET/PP2A axis via transcription factor VEZF1 to promote progression of ovarian cancer
TL;DR: In this paper , a global proteomics analysis identified SET binding protein 1 (SETBP1) as a crucial target of TRIM29, and the SETBP1/SET/Protein phosphatase 2 (PP2A) axis was confirmed to be required for the recovery of cancer stem cell (CSC)-like phenotype suppressed by TRIM 29 knockdown.
References
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Journal ArticleDOI
PP2A as a master regulator of the cell cycle
Nathan Wlodarchak,Yongna Xing +1 more
TL;DR: The involvement of PP2A in the regulation of three cell signaling pathways: wnt, mTOR and MAP kinase, as well as the G1→S transition, DNA synthesis and mitotic initiation are reviewed.
Journal ArticleDOI
Cell cycle checkpoint in cancer: a therapeutically targetable double-edged sword
TL;DR: Developing concepts on how targeting cell cycle checkpoints may provide substantial improvement to cancer therapy are summarized.
Journal ArticleDOI
An intrinsic S/G2 checkpoint enforced by ATR
Joshua C. Saldivar,Stephan Hamperl,Michael J. Bocek,Mingyu Chung,Thomas E. Bass,Fernanda Cisneros-Soberanis,Fernanda Cisneros-Soberanis,Kumiko Samejima,Linfeng Xie,James R. Paulson,William C. Earnshaw,David Cortez,Tobias Meyer,Karlene A. Cimprich +13 more
TL;DR: It is shown that cells transactivate the mitotic gene network as they exit the S phase through a CDK1 (cyclin-dependent kinase 1)–directed FOXM1 phosphorylation switch, which couples DNA replication with mitosis and preserves genome integrity by enforcing an S/G2 checkpoint.
Journal ArticleDOI
Spatial Positive Feedback at the Onset of Mitosis
TL;DR: It is proposed that spatial positive feedback ensures a rapid, complete, robust, and irreversible transition from interphase to mitosis and suggest that bistable spatiotemporal switches may be widespread in biological regulation.
Journal ArticleDOI
USP7 is a SUMO deubiquitinase essential for DNA replication
Emilio Lecona,Sara Rodriguez-Acebes,Julia Specks,Andrés J. López-Contreras,Isabel Ruppen,Matilde Murga,Javier Muñoz,Juan Méndez,Oscar Fernandez-Capetillo +8 more
TL;DR: This work identifies USP7 as a replisome-enriched SUMO deubiquitinase that is essential for DNA replication and provides a model explaining the differential accumulation of SUMO and Ub at replication forks and identifies an essential role ofUSP7 in DNA replication that should be considered in the development of USP6 inhibitors as anticancer agents.
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