The DOI matches its Crossref record; 78 of the 86 references it cites were found in a registry or an index.
Chk2/hCds1 functions as a DNA damage checkpoint in G1by stabilizing p53
Open accessAbstract
Chk2/hcds1, the human homolog of the Saccharomyces cerevisiae RAD53/SPK1 and Schizosaccharomyces pombe cds1 DNA damage checkpoint genes, encodes a protein kinase that is post-translationally modified after DNA damage. Like its yeast homologs, the Chk2/hCds1 protein phosphorylates Cdc25C in vitro, suggesting that it arrests cells in G 2 in response to DNA damage. We expressed Chk2/hCds1 in human cells and analyzed their cell cycle profile. Wild-type, but not catalytically inactive, Chk2/hCds1 led to G 1 arrest after DNA damage. The arrest was inhibited by cotransfection of a dominant-negative p53 mutant, indicating that Chk2/hCds1 acted upstream of p53. In vitro, Chk2/hCds1 phosphorylated p53 on Ser-20 and dissociated preformed complexes of p53 with Mdm2, a protein that targets p53 for degradation. In vivo, ectopic expression of wild-type Chk2/hCds1 led to increased p53 stabilization after DNA damage, whereas expression of a dominant-negative Chk2/hCds1 mutant abrogated both phosphorylation of p53 on Ser-20 and p53 stabilization. Thus, in response to DNA damage, Chk2/hCds1 stabilizes the p53 tumor suppressor protein leading to cell cycle arrest in G 1.
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In the citing paper
“and hChk2, in turn, phosphorylates yet another amino-terminal Ser residue (Ser 20) in p53”
From Cell cycle checkpoint signaling through the ATM and ATR kinases (2001) · cites this paper as Chehab et al. 2000
In the citing paper
“These phosphorylation events contribute to disrupting the p53-Mdm2 (Chehab et al., 2000; Shieh et al., 2000), and Mdm2-DAXX (Tang et al., 2013) interactions, as well as to the degradation of Mdm2 and Mdm4 (Stommel and Wahl, 2004; Chen et al., 2005; Pereg et al., 2005, 2006; LeBron et al., 2006).”
From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Chehab et al., 2000
In the citing paper
“ATM also activates Chk2, which in turn phosphorylates p53 on serine 20 and inhibits MDM2 binding (Shieh et al, 1997;Banin et al, 1998;Chehab et al, 2000;Shieh et al, 2000).”
From ATM and Chk2-dependent phosphorylation of MDMX contribute to p53 activation after DNA damage (2005) · cites this paper as Chehab et al, 2000
In the citing paper
“Studies using Chk2-null mice, Chk2-null HCT116 cells, and Chk2 siRNA resulted in different conclusions (Zhang et al, 1998;Chehab et al, 2000;Shieh et al, 2000;Ahn et al, 2003; Jallepalli et al, 2003).”
From ATM and Chk2-dependent phosphorylation of MDMX contribute to p53 activation after DNA damage (2005) · cites this paper as Chehab et al, 2000
In the citing paper
“Although a role of ATM in p53 response is well established, the significance of Chk2 is still a matter of debate.”
From ATM and Chk2-dependent phosphorylation of MDMX contribute to p53 activation after DNA damage (2005) · cites this paper as Chehab et al, 2000
In the citing paper
“ATM also activates Chk2, which in turn phosphorylates p53 on S20, which is a part of the MDM2-binding site (Shieh et al, 1997(Shieh et al, , 2000;;Banin et al, 1998;Chehab et al, 2000).”
From ATM activates p53 by regulating MDM2 oligomerization and E3 processivity (2009) · cites this paper as Chehab et al, 2000
In the citing paper
“p53 is phosphorylated at Ser20 by the checkpoint kinase Chk2 after IR, which results in p53's dissociation from Mdm2 and its subsequent stabilization”
From USP10 Regulates p53 Localization and Stability by Deubiquitinating p53 (2010) · cites this paper as Chehab et al., 2000
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Citations
Cites
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Mdm2 promotes the rapid degradation of p53
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Regulation of p53 stability by Mdm2
Kubbutat, M. H. G., Jones, S. N., & Vousden, K. H. (1997) · Nature · doi:10.1038/387299a0 · Cited by 3,312 · cited 2×
“Stabilization of p53 in cells exposed to IR or UV light is due to dissociation from Mdm2 (Shieh et al. 1997), a protein that targets p53 for degradation through the ubiquitin pathway (Haupt et al. 1997; Kubbutat et al. 1997; Midgley and Lane 1997).”
BackgroundMomand, J., Zambetti, G. P., Olson, D. C., George, D., & Levine, A. J. (1992) · Cell · doi:10.1016/0092-8674(92)90644-r · Cited by 3,113
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A Single Ataxia Telangiectasia Gene with a Product Similar to PI-3 Kinase
Savitsky, K., Bar-Shira, A., Gilad, S., Rotman, G., Ziv, Y., Vanagaite, L., Tagle, D. A., Smith, S., Uziel, T., Sfez, S., et al. (1995) · Science · doi:10.1126/science.7792600 · Cited by 2,785
Thymocyte apoptosis induced by p53-dependent and independent pathways
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Structure of the MDM2 Oncoprotein Bound to the p53 Tumor Suppressor Transactivation Domain
Kussie, P. H., Gorina, S., Marechal, V., Elenbaas, B., Moreau, J., Levine, A. J., & Pavletich, N. P. (1996) · Science · doi:10.1126/science.274.5289.948 · Cited by 2,206
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Metadata
- Authors
- Chehab, N. H., Malikzay, A., Appel, M., & Halazonetis, T. D.
- Affiliations
- The Wistar Institute (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2000-02-01
- Volume
- 14
- Issue
- 3
- Pages
- 278-288
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC316357
- OpenAlex
- W2131833681
- Cited by
- 805
- References
- 86
- Citations by year
- 2026: 8 · 2025: 5 · 2024: 8 · 2023: 11 · 2022: 19 · 2021: 17 · 2020: 18 · 2019: 11 · 2018: 11 · 2017: 10 · 2016: 25 · 2015: 16 · 2014: 28 · 2013: 27 · 2012: 29
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Cancer Society
- National Institutes of Health (CA-25874)
- National Cancer Institute (CA09171, CA-25874, CA-76367, R01CA076367, P01CA025874, T32CA009171)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- Chk2, DNA damage checkpoint, p53 stabilization, MDM2, G1 cell cycle arrest, Cdc25C phosphorylation, post-translational modification, tumor suppressor proteins, dominant-negative mutant
- MeSH terms
- DNA Damage, Humans, Nuclear Proteins, Phosphorylation, Protein Kinases, Proto-Oncogene Proteins, Tumor Cells, Cultured, Tumor Suppressor Protein p53, G1 Phase, Protein Serine-Threonine Kinases, Schizosaccharomyces pombe Proteins, Proto-Oncogene Proteins c-mdm2, Checkpoint Kinase 2
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