ArticleThe EMBO journal2021
USP7 limits CDK1 activity throughout the cell cycle.
Article in The EMBO journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
- Eriodictyol in Cancer Therapy: Reviewing Mechanistic Insights and Translational Opportunities.International journal of molecular sciences · 2026Review
- Regulatory roles of five key USP family deubiquitinases in cancer: from mechanisms to targeted therapy advances.Frontiers in pharmacology · 2026Review
- Ubiquitin specific protease 7 deubiquitinates and regulates Aurora B-mediated cytokinesis.BMB reports · 2025Article
- An inherited predisposition allele promotes gastric cancer via enhancing deubiquitination-mediated activation of epithelial-to-mesenchymal transition signaling.The Journal of clinical investigation · 2025Article
- CARM1 S217 phosphorylation by CDK1 in late G2 phase facilitates mitotic entry.Cell death & disease · 2025Article
- Targeting the USP7-CDK1 axis suppresses estrogen receptor-positive breast cancer progression.Cancer cell international · 2025Article
- CDK1 promotes the phosphorylation of KIFC1 to regulate the tumorgenicity of endometrial carcinoma.Journal of gynecologic oncology · 2024Article
- The role of USP7-YY1 interaction in promoting colorectal cancer growth and metastasis.Cell death & disease · 2024Article
- USP7 Deregulation Impairs S Phase Specific DNA Repair after Irradiation in Breast Cancer Cells.Biomedicines · 2024Article
- Deubiquitinases in cancer.Nature reviews. Cancer · 2023Review
- Inhibition of USP7 upregulates USP22 and activates its downstream cancer-related signaling pathways in human cancer cells.Cell communication and signaling : CCS · 2023Article
- Targeting CDK1 in cancer: mechanisms and implications.NPJ precision oncology · 2023Review
- Article
- Prognostic and immunological characteristics of CDK1 in lung adenocarcinoma: A systematic analysis.Frontiers in oncology · 2023Article
- Article
- Targeting E2F Sensitizes Prostate Cancer Cells to Drug-Induced Replication Stress by Promoting Unscheduled CDK1 Activity.Cancers · 2022Article
- USP7 regulates the ERK1/2 signaling pathway through deubiquitinating Raf-1 in lung adenocarcinoma.Cell death & disease · 2022Article
- p16 Represses DNA Damage Repair via a Novel Ubiquitin-Dependent Signaling Cascade.Cancer research · 2022Article
- Coordinating DNA Replication and Mitosis through Ubiquitin/SUMO and CDK1.International journal of molecular sciences · 2021Review
- Review
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chemical inhibitors of the deubiquitinase USP7 are currently being developed as anticancer agents based on their capacity to stabilize P53. Regardless of this activity, USP7 inhibitors also generate DNA damage in a p53-independent manner. However, the mechanism of this genotoxicity and its contribution to the anticancer effects of USP7 inhibitors are still under debate. Here we show that, surprisingly, even if USP7 inhibitors stop DNA replication, they also induce a widespread activation of CDK1 throughout the cell cycle, which leads to DNA damage and is toxic for mammalian cells. In addition, USP7 interacts with the phosphatase PP2A and supports its active localization in the cytoplasm. Accordingly, inhibition of USP7 or PP2A triggers very similar changes of the phosphoproteome, including a widespread increase in the phosphorylation of CDK1 targets. Importantly, the toxicity of USP7 inhibitors is alleviated by lowering CDK1 activity or by chemical activation of PP2A. Our work reveals that USP7 limits CDK1 activity at all cell cycle stages, providing a novel mechanism that explains the toxicity of USP7 inhibitors through untimely activation of CDK1.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.