The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
Chk1, but not Chk2, inhibits Cdc25 phosphatases by a novel common mechanism.
Open accessAbstract
Cdc25 phosphatases activate cyclin-dependent kinases (Cdks) and thereby promote cell cycle progression. In vertebrates, Chk1 and Chk2 phosphorylate Cdc25A at multiple N-terminal sites and target it for rapid degradation in response to genotoxic stress. Here we show that Chk1, but not Chk2, phosphorylates Xenopus Cdc25A at a novel C-terminal site (Thr504) and inhibits it from C-terminally interacting with various Cdk-cyclin complexes, including Cdk1-cyclin A, Cdk1-cyclin B, and Cdk2-cyclin E. Strikingly, this inhibition, rather than degradation itself, of Cdc25A is essential for the Chk1-induced cell cycle arrest and the DNA replication checkpoint in early embryos. 14-3-3 proteins bind to Chk1-phosphorylated Thr504, but this binding is not required for the inhibitory effect of Thr504 phosphorylation. A C-terminal site presumably equivalent to Thr504 exists in all known Cdc25 family members from yeast to humans, and its phosphorylation by Chk1 (but not Chk2) can also inhibit all examined Cdc25 family members from C-terminally interacting with their Cdk-cyclin substrates. Thus, Chk1 but not Chk2 seems to inhibit virtually all Cdc25 phosphatases by a novel common mechanism.
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“Chk1 then phosphorylates numerous downstream targets, including the Cdc25A phosphatase (Uto et al., 2004), which prompts Cdc25A proteasomal degradation (Mailand et al., 2000; Xiao et al., 2003).”
From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Uto et al., 2004
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Metadata
- Authors
- Uto, K., Inoue, D., Shimuta, K., Nakajo, N., & Sagata, N.
- Affiliations
- Kyushu University (JP)
- Corresponding author
- Sagata, Noriyuki
- ORCID
- Shimuta, Ken
- Venue
- The EMBO Journal
- Published
- 2004-07-22
- Volume
- 23
- Issue
- 16
- Pages
- 3386-3396
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC514503
- OpenAlex
- W2050348418
- Cited by
- 134
- References
- 47
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 7 · 2023: 5 · 2022: 4 · 2021: 9 · 2020: 6 · 2019: 5 · 2018: 2 · 2017: 5 · 2016: 4 · 2015: 4 · 2014: 10 · 2013: 9 · 2012: 6
- FWCI
- 3.56
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Science and Technology Agency (CREST)
- Core Research for Evolutional Science and Technology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Keywords
- Chk1, Chk2, CDC25A, Cdc25 phosphatase, cyclin-CDK complexes, CDK1/cyclin B, cyclin E/CDK2, DNA replication checkpoint, cell cycle arrest, 14-3-3 proteins, genotoxic stress, Xenopus embryo
- MeSH terms
- Checkpoint Kinase 1, Amino Acid Sequence, Animals, DNA Replication, Humans, Molecular Sequence Data, Mutation, Phosphorylation, Phosphothreonine, Protein Binding, Protein Kinases, Xenopus laevis, Cyclins, Sequence Alignment, Protein Serine-Threonine Kinases, cdc25 Phosphatases, Xenopus Proteins, 14-3-3 Proteins, Checkpoint Kinase 2
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