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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
The DNA damage response: putting checkpoints in perspective
Zhou, B.-B. S., & Elledge, S. J. (2000) · Nature · doi:10.1038/35044005 · Cited by 3,213
Checkpoints: Controls That Ensure the Order of Cell Cycle Events
Hartwell, L. H., & Weinert, T. A. (1989) · Science · doi:10.1126/science.2683079 · Cited by 3,053
Cell cycle checkpoint signaling through the ATM and ATR kinases
Abraham, R. T. (2001) · Genes & Development · doi:10.1101/gad.914401 · Cited by 1,966
Liu, Q., Guntuku, S., Cui, X.-S., Matsuoka, S., Cortez, D., Tamai, K., Luo, G., Carattini-Rivera, S., DeMayo, F., Bradley, A., et al. (2000) · Genes & Development · doi:10.1101/gad.14.12.1448 · Cited by 1,625
Chk1 and Chk2 kinases in checkpoint control and cancer
Bartek, J., & Lukas, J. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00110-7 · Cited by 1,513
Atm-Deficient Mice: A Paradigm of Ataxia Telangiectasia
Barlow, C., Hirotsune, S., Paylor, R. E., Liyanage, M., Eckhaus, M., Collins, F. S., Shiloh, Y., Crawley, J. N., Ried, T., Tagle, D. A., et al. (1996) · Cell · doi:10.1016/s0092-8674(00)80086-0 · Cited by 1,465
Peng, C.-Y., Graves, P. R., Thoma, R. S., Wu, Z., Shaw, A. S., & Piwnica-Worms, H. (1997) · Science · doi:10.1126/science.277.5331.1501 · Cited by 1,341
Linkage of ATM to Cell Cycle Regulation by the Chk2 Protein Kinase
Matsuoka, S. (1998) · Science · doi:10.1126/science.282.5395.1893 · Cited by 1,322
Sanchez, Y., Wong, C., Thoma, R. S., Richman, R., Wu, Z., Piwnica-Worms, H., & Elledge, S. J. (1997) · Science · doi:10.1126/science.277.5331.1497 · Cited by 1,320
The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA synthesis
Falck, J., Mailand, N., Syljuåsen, R. G., Bartek, J., & Lukas, J. (2001) · Nature · doi:10.1038/35071124 · Cited by 1,085
Flagged first, then by citations
Cited by
Sorted by citations
Items 101–137 of 137
KRCC1, a modulator of the DNA damage response
Neizer‐Ashun, F., Dwivedi, S. K. D., Dey, A., Thavathiru, E., Berry, W. L., Lees‐Miller, S. P., Mukherjee, P., & Bhattacharya, R. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac890 · Cited by 1
REGULATION OF CDK DEPHOSPHORYLATION
Lindqvist, A. (2005) · Figshare
Chk1 and Chk2 as Checkpoint Targets
Zhang, H., Xiao, Z., & Sowin, T. (2009) · Humana Press eBooks · doi:10.1007/978-1-60761-178-3_16 · Cited by 1
Sankunny, M. (2013) · D-Scholarship@Pitt (University of Pittsburgh)
Cyclin A/CDK2 regulates multiple G2 phase pathways
Oakes, V. (2012)
Regulation of DNA Double Strand Break Response
Chen, C. (2014) · DukeSpace (Duke University)
Study of the regulation and signalling of cdk2-Cyclin o complexes during apoptosis
Roset, R. (2008) · TDX (Tesis Doctorals en Xarxa)
Edwards, P. J. (2008) · Drug Discovery Today · doi:10.1016/j.drudis.2008.06.009
Interplay between ATM and ATR for the regulation of cellular responses to DNA damage
Fan, X. (2010) · DuEPublico (University of Duisburg-Essen)
The Role and Regulation of the Phosphatase PPM1D in Chemoresistant Gynecological Cancers
Ali, A. (2014) · uO Research (University of Ottawa) · doi:10.20381/ruor-3512
Post-translational Regulation of RPA32, ATM and Rad17 Controls the DNA Damage Response
Feng, J. (2009) · DukeSpace (Duke University)
Meccanismi di controllo della proliferazione delle cellule germinali primordiali
Sorrentino, E. (2007) · Cineca Institutional Research Information System (Tor Vergata University) · doi:10.58015/sorrentino-eleonora_phd2007-05
REGULATION OF CDK DEPHOSPHORYLATION
Lindqvist, A. (2005)
her2 hyper-activation through the production of carboxy-terminal fragments
Angelini, P. D. (2014) · TDX (Tesis Doctorals en Xarxa)
Chapter 16 Chk1 and Chk2 as Checkpoint Targets
Zhang, H., Xiao, Z., & Sowin, T. (2009)
REGULATION OF THE CDC25 MITOTIC INDUCER FOLLOWING REPLICATION ARREST AND DNA DAMAGE
Frazer, C. (2011) · QSpace (Queen's University Library)
RAD9A Stabilization and Destabilization Processes in Checkpoint Maintenance and Checkpoint Recovery
Zambrano, O., & Frend, W. H. C. (2015) · QSpace (Queen's University Library)
Carter, A. D. (2005) · VTechWorks (Virginia Tech)
Dravid, A. (2004) · VTechWorks (Virginia Tech)
The Role of Nej1-Lif1 in Double Strand Break Repair Pathway Choice and Non-Homologous End-Joining
Sorenson, K. (2017) · Libraries and Cultural Resources (University of Calgary) · doi:10.11575/prism/28337
Friedberg, E. C., Walker, G. C., Siede, W., Wood, R. D., Schultz, R. A., & Ellenberger, T. E. (2014) · ASM Press eBooks · doi:10.1128/9781555816704.ch21
KRCC1, a novel modulator of the DNA damage responsePreprint
Neizer‐Ashun, F., Dwivedi, S. K. D., Dey, A., Thavathiru, E., Berry, W. L., Lees‐Miller, S. P., Mukherjee, P., & Bhattacharya, R. (2022) · Research Square · doi:10.21203/rs.3.rs-1514922/v1
Chen, Y., Pereira, E., & Sánchez, Y. (2007) · AfCS-Nature Molecule Pages · doi:10.1038/mp.a000642.01
Uchida, S., Yoshioka, K., Kizu, R., Nakagama, H., Matsunaga, T., Ishizaka, Y., Poon, R. Y. C., & Yamashita, K. (2023) · doi:10.1158/0008-5472.c.6499226.v1
Ahmed, R. (2013) · University of Bedfordshire Repository (University of Bedfordshire)
Etude de l'organisation spatiale de la réparation des cassures double-brins de l'ADN
Choudjaye, J. (2016) · theses.fr (ABES) · doi:10.70675/32f25257z95d2z4be8zaf3dzb70b71274b8d
Origins of Cellular Lethality Resulting From a Defect in Homologous Recombination in Human Cells
THOMAS, M. L. (2021) · theses.fr (ABES) · doi:10.70675/294f7c6bz644bz42ddz8fb3zffd32551bc76
Regulation of the Akt/mTORC1 Pathway by HIV Transcriptional Activator Tat in B Cells
Akbay, B. (2021) · theses.fr (ABES) · doi:10.70675/2b579806z11cfz4545zb88az6987a56822bf · Cited by 1
BindingDB Entry 50045098: Development of synthetic lethality anticancer therapeutics.
BindingDB (2016) · UC San Diego · doi:10.7270/q2vd714c
Radiation Induced DNA Damage Checkpoints
Eriksson, D., Riklund, K., Johansson, L. F., & Stigbrand, T. I. (2008) · Springer eBooks · doi:10.1007/978-1-4020-8696-0_14
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
