The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.
USP7 counteracts SCFβTrCP- but not APCCdh1-mediated proteolysis of Claspin
Open accessAbstract
Claspin is an adaptor protein that facilitates the ataxia telangiectasia and Rad3-related (ATR)-mediated phosphorylation and activation of Chk1, a key effector kinase in the DNA damage response. Efficient termination of Chk1 signaling in mitosis and during checkpoint recovery requires SCFβTrCP-dependent destruction of Claspin. Here, we identify the deubiquitylating enzyme ubiquitin-specific protease 7 (USP7) as a novel regulator of Claspin stability. Claspin and USP7 interact in vivo, and USP7 is required to maintain steady-state levels of Claspin. Furthermore, USP7-mediated deubiquitylation markedly prolongs the half-life of Claspin, which in turn increases the magnitude and duration of Chk1 phosphorylation in response to genotoxic stress. Finally, we find that in addition to the M phase–specific, SCFβTrCP-mediated degradation, Claspin is destabilized by the anaphase-promoting complex (APC) and thus remains unstable in G1. Importantly, we demonstrate that USP7 specifically opposes the SCFβTrCP- but not APCCdh1-mediated degradation of Claspin. Thus, Claspin turnover is controlled by multiple ubiquitylation and deubiquitylation activities, which together provide a flexible means to regulate the ATR–Chk1 pathway.
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“USP7 also influences DSB repair by regulating checkpoint kinase 1 (Chk1) (Faustrup et al., 2009; Alonso-de Vega et al., 2014; Zhang P. et al., 2014).”
From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Faustrup et al., 2009
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“USP7 controls Chk1 signaling by deubiquitinating and stabilizing both Chk1 and its activator protein, Claspin (Faustrup et al., 2009; Alonso-de Vega et al., 2014; Zhang P. et al., 2014).”
From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Faustrup et al., 2009
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RNF8 Ubiquitylates Histones at DNA Double-Strand Breaks and Promotes Assembly of Repair Proteins
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Self-citationRapid Destruction of Human Cdc25A in Response to DNA Damage
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Self-citationDNA damage checkpoints: from initiation to recovery or adaptation
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Self-citationA dynamic role of HAUSP in the p53-Mdm2 pathway
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Spatial organization of the mammalian genome surveillance machinery in response to DNA strand breaks
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Self-citationThe Deubiquitinating Enzyme USP1 Regulates the Fanconi Anemia Pathway
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Regulation of monoubiquitinated PCNA by DUB autocleavage
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Gold, D. A. (2009) · CaltechTHESIS (California Institute of Technology) · doi:10.7907/xg90-5475
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McGarry, E. (2016) · Arrow@dit (Dublin Institute of Technology) · doi:10.13025/17576
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P22077 enhances the antitumor efficacy of Cisplatin and its mechanism
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USP7 maintains hematopoietic stem cell dormancy and function by stabilizing HMGA2Preprint
Nouhaud, A., Anna, D., Bouttier, M., Rigaud, Q., Enfedaque, P., Somaï, H., Hébrard, S., Prade, N., Dufrechou, S., Musiani, D., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.07.03.731117
Wang, Y., & Shi, J. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1933967
Metadata
- Authors
- Faustrup, H., Bekker-Jensen, S., Bartek, J., Lukas, J., & Mailand, N.
- Affiliations
- Institute of Cancer Biology and Centre for Genotoxic Stress Research, Danish Cancer Society, DK-2100 Copenhagen, Denmark
- Danish Cancer Society (DK)
- ORCID
- Mailand, Niels
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2009-01-05
- Volume
- 184
- Issue
- 1
- Pages
- 13-19
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2615094
- OpenAlex
- W2087983227
- Cited by
- 113
- References
- 23
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 1 · 2023: 4 · 2022: 5 · 2021: 10 · 2020: 7 · 2019: 8 · 2018: 9 · 2017: 7 · 2016: 12 · 2015: 6 · 2014: 11 · 2013: 9 · 2012: 5
- FWCI
- 2.41
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- National Center for Chronic Disease Prevention and Health Promotion (U58 DP006009)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Keywords
- Claspin, USP7, deubiquitination, anaphase-promoting complex, CDH1, protein stability, Chk1 phosphorylation, ATR-Chk1 pathway, DNA damage response, spindle assembly checkpoint, ubiquitination, genotoxic stress
- MeSH terms
- Checkpoint Kinase 1, Ubiquitin-Specific Peptidase 7, Cell Line, DNA Damage, Humans, Phosphorylation, Protein Kinases, Substrate Specificity, G1 Phase, Ubiquitin Thiolesterase, Ubiquitin-Protein Ligase Complexes, SKP Cullin F-Box Protein Ligases, Adaptor Proteins, Signal Transducing, Ubiquitination, Anaphase-Promoting Complex-Cyclosome
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