Chk2/hCds1 functions as a DNA damage checkpoint in G1by stabilizing p53

Chehab, Nabil H.; Malikzay, Asra; Appel, Michael; Halazonetis, Thanos D.

doi:10.1101/gad.14.3.278

Cited by 806Cancer-related Molecular PathwaysDNA Repair MechanismsProtein Kinase Regulation and GTPase Signaling

Chk2/hCds1 functions as a DNA damage checkpoint in G1by stabilizing p53

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Chehab, Nabil H., Malikzay, Asra, Appel, Michael, Halazonetis, Thanos D.·2000·Genes & Development

DOI 10.1101/gad.14.3.278PMC PMC316357

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Abstract

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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hChk2 phosphorylates p53 at Ser20.
“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
These phosphorylation events disrupt p53-Mdm2 and Mdm2-DAXX interactions and promote degradation of Mdm2 and Mdm4.
“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
ATM activates Chk2, which phosphorylates p53 on serine 20 and inhibits MDM2 binding.
“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
Different conclusions have emerged from work with Chk2-null mice, Chk2-null HCT116 cells, and Chk2 small interfering RNA.
“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
The role of ATM in p53 response is well established, but the significance of Chk2 is debated.
“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

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p53, the cellular gatekeeper for growth and division
Levine, A. J. (1997) · Cell · doi:10.1016/s0092-8674(00)81871-1 · Cited by 7,693 · see citing works
Mdm2 promotes the rapid degradation of p53
Haupt, Y., Maya, R., Kazaz, A., & Oren, M. (1997) · Nature · doi:10.1038/387296a0 · Cited by 4,506 · see citing works
Participation of p53 protein in the cellular response to DNA damage.
Kastan, M. B., Onyekwere, O. C., Sidransky, D., Vogelstein, B., & Craig, R. W. (1991) · PubMed · Cited by 3,761 · see citing works
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 · see citing works
The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation
Momand, 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 · see citing works
A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia
Kastan, M. B., Zhan, Q., El-Deiry, W. S., Carrier, F., Jacks, T., Walsh, W. V., Plunkett, B. S., Vogelstein, B., & Fornace, A. J. (1992) · Cell · doi:10.1016/0092-8674(92)90593-2 · Cited by 3,047 · see citing works
p53 is required for radiation-induced apoptosis in mouse thymocytes
Lowe, S. W., Schmitt, E. M., Smith, S. W., Osborne, B. A., & Jacks, T. (1993) · Nature · doi:10.1038/362847a0 · Cited by 2,864 · see citing works
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 · see citing works
Thymocyte apoptosis induced by p53-dependent and independent pathways
Clarke, A. R., Purdie, C. A., Harrison, D. J., Morris, R. G., Bird, C. C., Hooper, M. L., & Wyllie, A. H. (1993) · Nature · doi:10.1038/362849a0 · Cited by 2,271 · see citing works
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 · see citing works
DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2
Shieh, S.-Y., Ikeda, M., Taya, Y., & Prives, C. (1997) · Cell · doi:10.1016/s0092-8674(00)80416-x · Cited by 2,100 · see citing works
Cell Cycle Checkpoints: Preventing an Identity Crisis
Elledge, S. J. (1996) · Science · doi:10.1126/science.274.5293.1664 · Cited by 2,047 · see citing works
Activation of the ATM Kinase by Ionizing Radiation and Phosphorylation of p53
Canman, C. E., Lim, D.-S., Cimprich, K. A., Taya, Y., Tamai, K., Sakaguchi, K., Appella, E., Kastan, M. B., & Siliciano, J. D. (1998) · Science · doi:10.1126/science.281.5383.1677 · Cited by 2,042 · see citing works
Wild-type p53 is a cell cycle checkpoint determinant following irradiation.
Kuerbitz, S. J., Plunkett, B., Walsh, W., & Kastan, M. B. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.16.7491 · Cited by 1,837 · see citing works
Enhanced Phosphorylation of p53 by ATM in Response to DNA Damage
Banin, S., Moyal, L., Shieh, S.-Y., Taya, Y., Anderson, C. W., Chessa, L., Smorodinsky, N. I., Prives, C., Reiss, Y., Shiloh, Y., et al. (1998) · Science · doi:10.1126/science.281.5383.1674 · Cited by 1,797 · see citing works
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 · see citing works
Conservation of the Chk1 Checkpoint Pathway in Mammals: Linkage of DNA Damage to Cdk Regulation Through Cdc25
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 · see citing works
DNA damage activates p53 through a phosphorylation–acetylation cascade
Sakaguchi, K., Herrera, J. E., Saito, S., Miki, T., Bustin, M., Vassilev, A., Anderson, C. W., & Appella, E. (1998) · Genes & Development · doi:10.1101/gad.12.18.2831 · Cited by 1,204 · see citing works
Primary structure and functional expression from complementary DNA of a human interleukin-1 receptor antagonist
Eisenberg, S. P., Evans, R. J., Arend, W. P., Verderber, E. L., Brewer, M. T., Hannum, C. H., & Thompson, R. C. (1990) · Nature · doi:10.1038/343341a0 · Cited by 1,088 · see citing works
A role for ATR in the DNA damage-induced phosphorylation of p53
Tibbetts, R. S., Brumbaugh, K. M., Williams, J. M., Sarkaria, J. N., Cliby, W. A., Shieh, S.-Y., Taya, Y., Prives, C., & Abraham, R. T. (1999) · Genes & Development · doi:10.1101/gad.13.2.152 · Cited by 1,046 · see citing works
The human homologs of checkpoint kinases Chk1 and Cds1 (Chk2) phosphorylate p53 at multiple DNA damage-inducible sites.
Shieh, S.-Y., Ahn, J., Tamai, K., Taya, Y., & Prives, C. (2000) · Genes & Development · doi:10.1101/gad.14.3.289 · Cited by 972 · see citing works
Heterozygous Germ Line hCHK2 Mutations in Li-Fraumeni Syndrome
Bell, D. W., Varley, J. M., Szydlo, T. E., Kang, D. H., Wahrer, D. C. R., Shannon, K. E., Lubratovich, M. L., Verselis, S. J., Isselbacher, K. J., Fraumeni, J. F., et al. (1999) · Science · doi:10.1126/science.286.5449.2528 · Cited by 899 · see citing works
UV Irradiation Stimulates Levels of p53 Cellular Tumor Antigen in Nontransformed Mouse Cells
Maltzman, W., & Czyzyk, L. (1984) · Molecular and Cellular Biology · doi:10.1128/mcb.4.9.1689 · Cited by 893 · see citing works
DNA damage induces phosphorylation of the amino terminus of p53
Siliciano, J. D., Canman, C. E., Taya, Y., Sakaguchi, K., Appella, E., & Kastan, M. B. (1997) · Genes & Development · doi:10.1101/gad.11.24.3471 · Cited by 818 · see citing works
p53 Sites Acetylated In Vitro by PCAF and p300 Are Acetylated In Vivo in Response to DNA Damage
Liu, L., Scolnick, D. M., Trievel, R. C., Zhang, H. B., Marmorstein, R., Halazonetis, T. D., & Berger, S. L. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.2.1202 · Cited by 776 · see citing works
Self-citation
Differential induction of transcriptionally active p53 following UV or lonizing radiation: Defects in chromosome instability syndromes?
Lü, X. (1993) · Cell · doi:10.1016/0092-8674(93)90496-d · Cited by 772 · see citing works
Induction of nuclear accumulation of the tumor-suppressor protein p53 by DNA-damaging agents.
Fritsche, M., Haessler, C., & Brandner, G. (1993) · PubMed · Cited by 763 · see citing works
Nucleo‐cytoplasmic shuttling of the hdm2 oncoprotein regulates the levels of the p53 protein via a pathway used by the human immunodeficiency virus rev protein
Roth, J., Dobbelstein, M., Freedman, D. A., Shenk, T., & Levine, A. J. (1998) · The EMBO Journal · doi:10.1093/emboj/17.2.554 · Cited by 610 · see citing works
Regulation of RAD53 by the ATM -Like Kinases MEC1 and TEL1 in Yeast Cell Cycle Checkpoint Pathways
Sanchez, Y., Desany, B. A., Jones, W. J., Liu, Q., Wang, B., & Elledge, S. J. (1996) · Science · doi:10.1126/science.271.5247.357 · Cited by 585 · see citing works
Phosphorylation of Ser-20 mediates stabilization of human p53 in response to DNA damage.
Chehab, N. H., Malikzay, A., Stavridi, E. S., & Halazonetis, T. D. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.24.13777 · Cited by 583 · see citing works
Self-citation
Cdc25 Mitotic Inducer Targeted by Chk1 DNA Damage Checkpoint Kinase
Furnari, B. A., Rhind, N., & Russell, P. R. (1997) · Science · doi:10.1126/science.277.5331.1495 · Cited by 542 · see citing works
Control of the DNA damage checkpoint by Chk1 and Rad53 protein kinases through distinct mechanisms
Sanchez, Y., Bachant, J., Wang, H., Hu, F., Liu, D., Tetzlaff, M., & Elledge, S. J. (1999) · Science · doi:10.1126/science.286.5442.1166 · Cited by 536 · see citing works
A reversible, p53-dependent G0/G1 cell cycle arrest induced by ribonucleotide depletion in the absence of detectable DNA damage.Preprint
Linke, S. P., Clarkin, K., Leonardo, A. D., Tsou, A.-P., & Wahl, G. M. (1996) · Genes & Development · doi:10.1101/gad.10.8.934 · Cited by 531 · see citing works
ATM associates with and phosphorylates p53: mapping the region of interaction
Khanna, K. K., Keating, K. E., Kozlov, S., Scott, S. P., Gatei, M. H., Hobson, K., Taya, Y., Gabrielli, B. G., Chan, D. W., Lees‐Miller, S. P., et al. (1998) · Nature Genetics · doi:10.1038/3882 · Cited by 481 · see citing works
ATM-dependent activation of p53 involves dephosphorylation and association with 14-3-3 proteins
Waterman, M. J. F., Stavridi, E. S., Waterman, J. L. F., & Halazonetis, T. D. (1998) · Nature Genetics · doi:10.1038/542 · Cited by 457 · see citing works
Self-citation
Regulation of p53 function and stability by phosphorylation.
Ashcroft, M., Kubbutat, M. H. G., & Vousden, K. H. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.3.1751 · Cited by 452 · see citing works
rad -Dependent Response of the chk1 -Encoded Protein Kinase at the DNA Damage Checkpoint
Walworth, N. C., & Bernards, R. (1996) · Science · doi:10.1126/science.271.5247.353 · Cited by 397 · see citing works
S-phase-specific activation of Cds1 kinase defines a subpathway of the checkpoint response in Schizosaccharomyces pombePreprint
Lindsay, H. D., Griffiths, D. J. F., Edwards, R. J., Christensen, P. U., Murray, J. M., Osman, F., Walworth, N. C., & Carr, A. M. (1998) · Genes & Development · doi:10.1101/gad.12.3.382 · Cited by 385 · see citing works
The Schizosaccharomyces pombe rad3 checkpoint gene.
Bentley, N. J., Holtzman, D. A., Flaggs, G., Keegan, K. S., DeMaggio, A. J., Ford, J. C., Hoekstra, M. F., & Carr, A. M. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb01054.x · Cited by 366 · see citing works
Critical role for Ser20 of human p53 in the negative regulation of p53 by Mdm2
Unger, T., Juven‐Gershon, T., Moallem, E., Berger, M., Sionov, R. V., Lozano, G., Oren, M., & Haupt, Y. (1999) · The EMBO Journal · doi:10.1093/emboj/18.7.1805 · Cited by 365 · see citing works
Replication checkpoint requires phosphorylation of the phosphatase Cdc25 by Cds1 or Chk1
Zeng, Y., Forbes, K. C., Wu, Z., Moreno, S., Piwnica-Worms, H. M., & Enoch, T. (1998) · Nature · doi:10.1038/26766 · Cited by 341 · see citing works
Replication Checkpoint Enforced by Kinases Cds1 and Chk1
Boddy, M. N., Furnari, B., Mondesert, O., & Russell, P. (1998) · Science · doi:10.1126/science.280.5365.909 · Cited by 316 · see citing works
p53 protein stability in tumour cells is not determined by mutation but is dependent on Mdm2 binding
MIDGLEY, C. A., & Lane, D. P. (1997) · Oncogene · doi:10.1038/sj.onc.1201459 · Cited by 313 · see citing works
A human homologue of the checkpoint kinase Cds1 directly inhibits Cdc25 phosphatase
Blasina, A., de Weyer, I. V., Laus, M. C., Luyten, W. H. M. L., Parker, A. E., & McGowan, C. H. (1999) · Current Biology · doi:10.1016/s0960-9822(99)80041-4 · Cited by 301 · see citing works
Spk1/Rad53 is regulated by Mec1-dependent protein phosphorylation in DNA replication and damage checkpoint pathways.
Sun, Z., Fay, D. S., Marini, F., Foiani, M., & Stern, D. F. (1996) · Genes & Development · doi:10.1101/gad.10.4.395 · Cited by 300 · see citing works
DNA damage‐inducible phosphorylation of p53 at N‐terminal sites including a novel site, Ser20, requires tetramerization
Shieh, S.-Y., Taya, Y., & Prives, C. (1999) · The EMBO Journal · doi:10.1093/emboj/18.7.1815 · Cited by 299 · see citing works
cDNA cloning and gene mapping of a candidate human cell cycle checkpoint protein.
Cimprich, K. A., Shin, T. B., Keith, C. T., & Schreiber, S. L. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.7.2850 · Cited by 273 · see citing works
Cdc7p–Dbf4p kinase binds to chromatin during S phase and is regulated by both the APC and the RAD53 checkpoint pathway
Weinreich, M., & Stillman, B. (1999) · The EMBO Journal · doi:10.1093/emboj/18.19.5334 · Cited by 268 · see citing works
A human Cds1-related kinase that functions downstream of ATM protein in the cellular response to DNA damage
Brown, A. L., Lee, C. H., Schwarz, J. K., Mitiku, N., Piwnica-Worms, H. M., & Chung, J. H. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.7.3745 · Cited by 260 · see citing works
DNA Damage and Checkpoint Pathways
Weinert, T. A. (1998) · Cell · doi:10.1016/s0092-8674(00)81597-4 · Cited by 253 · see citing works
Ionizing radiation and UV induction of p53 protein by different pathways in ataxia-telangiectasia cells.
Khanna, K. K., & Lavin, M. F. (1993) · PubMed · Cited by 248 · see citing works
The p53-dependent G1 cell cycle checkpoint pathway and ataxia-telangiectasia.
Canman, C. E., Wolff, A. C., Chen, C.-Y., Fornace, A. J., & Kastan, M. B. (1994) · PubMed · Cited by 246 · see citing works
The structural basis for spectral variations in green fluorescent protein
Palm, G. J., Zdanov, A. S., Gaitanaris, G., Stauber, R. H., Pavlakis, G. N., & Wlodawer, A. (1997) · Nature Structural & Molecular Biology · doi:10.1038/nsb0597-361 · Cited by 243 · see citing works
UV Irradiation Stimulates Levels of p53 Cellular Tumor Antigen in Nontransformed Mouse Cells
Maltzman, W., & Czyzyk, L. (1984) · Molecular and Cellular Biology · doi:10.1128/mcb.4.9.1689-1694.1984 · Cited by 226 · see citing works
Functional activation of p53 via phosphorylation following DNA damage by UV but not γ radiation
Kapoor, M., & Lozano, G. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.6.2834 · Cited by 209 · see citing works
A functionally inactive p53 protein interatocarcinoma cells is activated by either DNA damage or cellular differentiation
Lutzker, S. G., & Levine, A. J. (1996) · Nature Medicine · doi:10.1038/nm0796-804 · Cited by 206 · see citing works
p53 is phosphorylated in vitro and in vivo by the delta and epsilon isoforms of casein kinase 1 and enhances the level of casein kinase 1 delta in response to topoisomerase-directed drugs
Knippschild, U., Milne, D., Campbell, L. E., DeMaggio, A. J., Christenson, E., Hoekstra, M. F., & Meek, D. W. (1997) · Oncogene · doi:10.1038/sj.onc.1201541 · Cited by 172 · see citing works
RAD9 and DNA polymerase epsilon form parallel sensory branches for transducing the DNA damage checkpoint signal in Saccharomyces cerevisiae.Preprint
Navas, T. A., Sánchez, Y., & Elledge, S. J. (1996) · Genes & Development · doi:10.1101/gad.10.20.2632 · Cited by 167 · see citing works
Ultraviolet radiation, but not γ radiation or etoposide-induced DNA damage, results in the phosphorylation of the murine p53 protein at serine-389
Lu, H., Taya, Y., Ikeda, M., & Levine, A. J. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.11.6399 · Cited by 162 · see citing works
The anaphase inhibitor of Saccharomyces cerevisiae Pds1p is a target of the DNA damage checkpoint pathway
Cohen‐Fix, O., & Koshland, D. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.26.14361 · Cited by 158 · see citing works
DNA damage induced p53 stabilization: no indication for an involvement of p53 phosphorylation
Blattner, C., Tobiasch, E., Litfen, M., Rahmsdorf, H. J., & Herrlich, P. (1999) · Oncogene · doi:10.1038/sj.onc.1202480 · Cited by 151 · see citing works
Rad53-dependent phosphorylation of Swi6 and down-regulation of CLN1 andCLN2 transcription occur in response to DNA damage inSaccharomyces cerevisiaePreprint
Sidorova, J. M., & Breeden, L. L. (1997) · Genes & Development · doi:10.1101/gad.11.22.3032 · Cited by 150 · see citing works
An Inhibitor of Nuclear Export Activates the p53 Response and Induces the Localization of HDM2 and p53 to U1A-Positive Nuclear Bodies Associated with the PODs
Laı́n, S., Midgley, C., Sparks, A., Lane, E. B., & Lane, D. P. (1999) · Experimental Cell Research · doi:10.1006/excr.1999.4433 · Cited by 135 · see citing works
A p53-dependent S-phase checkpoint helps to protect cells from DNA damage in response to starvation for pyrimidine nucleotides
Agarwal, M. L., Agarwal, A. M., Taylor, W. R., Chernova, O. B., Sharma, Y., & Stark, G. R. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.25.14775 · Cited by 110 · see citing works
Basis for the Checkpoint Signal Specificity That Regulates Chk1 and Cds1 Protein Kinases
Brondello, J., Boddy, M. N., Furnari, B. A., & Russell, P. R. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.6.4262 · Cited by 108 · see citing works
DNA damage triggers DRB-resistant phosphorylation of human p53 at the CK2 site
Blaydes, J. P., & Hupp, T. R. (1998) · Oncogene · doi:10.1038/sj.onc.1202014 · Cited by 107 · see citing works
Atm-dependent interactions of a mammalian Chk1 homolog with meiotic chromosomes
Flaggs, G., Plug, A. W., Dunks, K. M., Mundt, K., Ford, J. C., Quiggle, M. R. E., Taylor, E. M., Westphal, C. H., Ashley, T., Hoekstra, M. F., et al. (1997) · Current Biology · doi:10.1016/s0960-9822(06)00417-9 · Cited by 105 · see citing works
Role of Human Cds1 (Chk2) Kinase in DNA Damage Checkpoint and Its Regulation by p53
Tominaga, K., Morisaki, H., Kaneko, Y. S., Fujimoto, A., Tanaka, T., Ohtsubo, M., Hirai, M., Okayama, H., Ikeda, K., & Nakanishi, M. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.44.31463 · Cited by 100 · see citing works
Identification of an additional negative regulatory region for p53 sequence-specific DNA binding
Müller‐Tiemann, B., Halazonetis, T. D., & Elting, J. J. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.11.6079 · Cited by 89 · see citing works
Self-citation
Structure–based rescue of common tumor–derived p53 mutants
Wieczorek, A. M., Waterman, J. L. F., Waterman, M. J. F., & Halazonetis, T. D. (1996) · Nature Medicine · doi:10.1038/nm1096-1143 · Cited by 89 · see citing works
Self-citation
Diminished capacity for p53 in mediating a radiation-induced G1 arrest in established human tumor cell lines.
Li, C., Nagasawa, H., Dahlberg, W. K., & Jb, L. (1995) · PubMed · Cited by 55 · see citing works
The p53 activation and apoptosis induced by DNA damage are reversibly inhibited by salicylate
Chernov, M. V., & Stark, G. R. (1997) · Oncogene · doi:10.1038/sj.onc.1201104 · Cited by 46 · see citing works
p53 Transactivation and Protein Accumulation Are Independently Regulated by UV Light in Different Phases of the Cell Cycle
Haapajärvi, T., Pitkänen, K., Tsubari, M., & Laiho, M. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.6.3074 · Cited by 36 · see citing works
Absence of a radiation-induced first-cycle G1-S arrest in p53+ human tumor cells synchronized by mitotic selection.
Nagasawa, H., Keng, P., Maki, C. G., Yu, Y., & Little, J. B. (1998) · PubMed · Cited by 35 · see citing works
Loss of normal G1 checkpoint control is an early step in carcinogenesis, independent of p53 status.
Syljuåsen, R. G., Krolewski, B., & Little, J. B. (1999) · PubMed · Cited by 27 · see citing works
Change in oligomerization specificity of the p53 tetramerization domain by hydrophobic amino acid substitutions
Stavridi, E. S., Caruso, L. C., Chehab, N. H., & Halazonetis, T. D. (1999) · Protein Science · doi:10.1110/ps.8.9.1773 · Cited by 15 · see citing works
Self-citation
Separate pathways for p53 induction by ionizing radiation and N-(phosphonoacetyl)-L-aspartate.
Chen, C. Y., Hall, I. J., Lansing, T. J., Gilmer, T. M., Tlsty, T. D., & Kastan, M. B. (1996) · PubMed · Cited by 13 · see citing works
Many faces of ATM: Eighth International Workshop on Ataxia-Telangiectasia
Halazonetis, T. D., & Shiloh, Y. (1999) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/s0304-419x(99)00023-2 · Cited by 12 · see citing works
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DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation
Bakkenist, C. J., & Kastan, M. B. (2003) · Nature · doi:10.1038/nature01368 · Cited by 3,466 · see citing works
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 · see citing works
A DNA damage checkpoint response in telomere-initiated senescence
Fagagna, F. D. D., Reaper, P. M., Clay-Farrace, L., Fiegler, H., Carr, P., von Zglinicki, T., Saretzki, G., Carter, N. P., & Jackson, S. P. (2003) · Nature · doi:10.1038/nature02118 · Cited by 2,855 · see citing works
Somatic mutations affect key pathways in lung adenocarcinoma
Ding, L., Getz, G., Wheeler, D. A., Mardis, E. R., McLellan, M. D., Cibulskis, K., Sougnez, C., Greulich, H., Muzny, D. M., Morgan, M. B., et al. (2008) · Nature · doi:10.1038/nature07423 · Cited by 2,681 · see citing works
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 · see citing works
Chk1 is an essential kinase that is regulated by Atr and required for the G 2 /M DNA damage checkpoint
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 · see citing works
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 · see citing works
Cell cycle control in cancer
Matthews, H. K., Bertoli, C., & de Bruin, R. A. M. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00404-3 · Cited by 1,506 · see citing works
The ATM–Chk2 and ATR–Chk1 Pathways in DNA Damage Signaling and Cancer
Smith, J., Tho, L. M., Xu, N., & Gillespie, D. A. (2010) · Advances in cancer research · doi:10.1016/b978-0-12-380888-2.00003-0 · Cited by 1,279 · see citing works
Cell death by mitotic catastrophe: a molecular definition
Castedo, M., Perfettini, J.-L., Roumier, T., Andreau, K., Medema, R., & Kroemer, G. (2004) · Oncogene · doi:10.1038/sj.onc.1207528 · Cited by 1,269 · see citing works
p53AIP1, a Potential Mediator of p53-Dependent Apoptosis, and Its Regulation by Ser-46-Phosphorylated p53
Oda, K., Arakawa, H., Tanaka, T., Matsuda, K., Tanikawa, C., Mori, T., Nishimori, H., Tamai, K., Tokino, T., Nakamura, Y., et al. (2000) · Cell · doi:10.1016/s0092-8674(00)00073-8 · Cited by 1,162 · see citing works
Low-penetrance susceptibility to breast cancer due to CHEK2*1100delC in noncarriers of BRCA1 or BRCA2 mutations
The CHEK2-Breast Cancer Consortium (2002) · Nature Genetics · doi:10.1038/ng879 · Cited by 1,104 · see citing works
Role of cell cycle in mediating sensitivity to radiotherapy
Pawlik, T. M., & Keyomarsi, K. (2004) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2004.03.005 · Cited by 1,101 · see citing works
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 · see citing works
Post‐translational modifications and activation of p53 by genotoxic stresses
Appella, E., & Anderson, C. W. (2001) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.2001.02225.x · Cited by 1,071 · see citing works
Decision making by p53: life, death and cancer
Oren, M. (2003) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401183 · Cited by 1,063 · see citing works
BRCA1 and BRCA2: 1994 and beyond
Narod, S. A., & Foulkes, W. D. (2004) · Nature Reviews Cancer · doi:10.1038/nrc1431 · Cited by 967 · see citing works
The human homologs of checkpoint kinases Chk1 and Cds1 (Chk2) phosphorylate p53 at multiple DNA damage-inducible sites.
Shieh, S.-Y., Ahn, J., Tamai, K., Taya, Y., & Prives, C. (2000) · Genes & Development · doi:10.1101/gad.14.3.289 · Cited by 972 · see citing works
P53 Binding Protein 1 (53bp1) Is an Early Participant in the Cellular Response to DNA Double-Strand Breaks
Schultz, L. B., Chehab, N. H., Malikzay, A., & Halazonetis, T. D. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.151.7.1381 · Cited by 897 · see citing works
Self-citation
DNA damage-induced cell death: From specific DNA lesions to the DNA damage response and apoptosis
Roos, W. P., & Kaina, B. (2013) · Cancer Letters · doi:10.1016/j.canlet.2012.01.007 · Cited by 879 · see citing works
Ataxia telangiectasia-mutated phosphorylates Chk2 in vivo and in vitro
Matsuoka, S., Rotman, G., Ogawa, A., Shiloh, Y., Tamai, K., & Elledge, S. J. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.190030497 · Cited by 830 · see citing works
The MDM2-p53 interaction.
Moll, U. M., & Petrenko, O. (2003) · PubMed · Cited by 778 · see citing works
The many substrates and functions of ATM.
Kastan, M. B., & Lim, D.-S. (2000) · Nature Reviews Molecular Cell Biology · doi:10.1038/35043058 · Cited by 779 · see citing works
Toward Maintaining the Genome: DNA Damage and Replication Checkpoints
Nyberg, K. A., Michelson, R. J., Putnam, C. W., & Weinert, T. A. (2002) · Annual Review of Genetics · doi:10.1146/annurev.genet.36.060402.113540 · Cited by 770 · see citing works
Ubiquitination, phosphorylation and acetylation: the molecular basis for p53 regulation
Brooks, C. L., & Gu, W. J. (2003) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(03)00003-6 · Cited by 742 · see citing works
Regulation and function of the p53 tumor suppressor protein
Ryan, K. M., Phillips, A. C., & Vousden, K. H. (2001) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(00)00216-7 · Cited by 721 · see citing works
Acetylation of p53 Activates Transcription through Recruitment of Coactivators/Histone Acetyltransferases
Barlev, N. A., Liu, L., Chehab, N. H., Mansfield, K., Harris, K. G., Halazonetis, T. D., & Berger, S. L. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00414-2 · Cited by 710 · see citing works
Self-citation
USP10 Regulates p53 Localization and Stability by Deubiquitinating p53
Yuan, J., Luo, K., Zhang, L., Cheville, J. C., & Lou, Z. (2010) · Cell · doi:10.1016/j.cell.2009.12.032 · Cited by 637 · see citing works
“For example, p53 is phosphorylated at Ser20 by the checkpoint kinase Chk2 after IR, which results in p53’s dissociation from Mdm2 and its subsequent stabilization (Chehab et al., 2000; Hirao et al., 2000; Shieh et al., 2000).”
ATM and ATR as therapeutic targets in cancer
Weber, A. M., & Ryan, A. J. (2014) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2014.12.001 · Cited by 644 · see citing works
Cellular Responses to DNA Damage
Norbury, C. J., & Hickson, I. D. (2001) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.41.1.367 · Cited by 628 · see citing works
Regulation of HDM2 activity by the ribosomal protein L11
Lohrum, M. A. E., Ludwig, R. L., Kubbutat, M. H. G., Hanlon, M., & Vousden, K. H. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00134-x · Cited by 626 · see citing works
ATM and ATR: networking cellular responses to DNA damage
Shiloh, Y. (2001) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(00)00159-3 · Cited by 601 · see citing works
The molecular biology of cancer
Bertram, J. S. (2000) · Molecular Aspects of Medicine · doi:10.1016/s0098-2997(00)00007-8 · Cited by 592 · see citing works
Generation of oscillations by the p53-Mdm2 feedback loop: A theoretical and experimental study
Bar‐Or, R. L., Maya, R. B.-Y., Segel, L. A., Alon, U., Levine, A. J., & Oren, M. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.210171597 · Cited by 579 · see citing works
Mechanisms of human DNA repair: an update
Christmann, M., Tomicic, M. T., Roos, W. P., & Kaina, B. (2003) · Toxicology · doi:10.1016/s0300-483x(03)00287-7 · Cited by 578 · see citing works
Mammalian G1- and S-phase checkpoints in response to DNA damage
Bártek, J., & Lukas, J. (2001) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(00)00280-5 · Cited by 573 · see citing works
Ribosomal Protein L11 Negatively Regulates Oncoprotein MDM2 and Mediates a p53-Dependent Ribosomal-Stress Checkpoint Pathway
Zhang, Y., Wolf, G. W., Bhat, K., Jin, A., Allio, T., Burkhart, W., & Xiong, Y. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.23.8902-8912.2003 · Cited by 556 · see citing works
Mrc1 transduces signals of DNA replication stress to activate Rad53
Alcasabas, A. A., Osborn, A. J., Bachant, J., Hu, F., Werler, P., Bousset, K., Furuya, K., Diffley, J. F. X., Carr, A. M., & Elledge, S. J. (2001) · Nature Cell Biology · doi:10.1038/ncb1101-958 · Cited by 516 · see citing works
P53 and radiation responses
Fei, P., & El‐Deiry, W. S. (2003) · Oncogene · doi:10.1038/sj.onc.1206677 · Cited by 497 · see citing works
p53 and E2f: partners in life and death
Polager, S., & Ginsberg, D. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2718 · Cited by 498 · see citing works
Modification of p53 with O-linked N-acetylglucosamine regulates p53 activity and stability
Yang, W. H., Kim, J. E., Nam, H. W., Ju, J., Kim, H. S., Kim, Y. S., & Cho, J. W. (2006) · Nature Cell Biology · doi:10.1038/ncb1470 · Cited by 489 · see citing works
Distinct spatiotemporal dynamics of mammalian checkpoint regulators induced by DNA damage.
Lukas, C., Falck, J., Bartkova, J., Bartek, J., & Lukas, J. (2003) · Nature Cell Biology · doi:10.1038/ncb945 · Cited by 474 · see citing works
Cell cycle checkpoint signaling:
Pietenpol, J. A., & Stewart, Z. A. (2002) · Toxicology · doi:10.1016/s0300-483x(02)00460-2 · Cited by 472 · see citing works
Pathways governing G1/S transition and their response to DNA damage
Bartek, J. J., & Lukas, J. (2001) · FEBS Letters · doi:10.1016/s0014-5793(01)02114-7 · Cited by 467 · see citing works
CHEK2*1100delC and Susceptibility to Breast Cancer: A Collaborative Analysis Involving 10,860 Breast Cancer Cases and 9,065 Controls from 10 Studies
* (2004) · The American Journal of Human Genetics · doi:10.1086/421251 · Cited by 466 · see citing works
A CHEK2 Genetic Variant Contributing to a Substantial Fraction of Familial Breast Cancer
Vahteristo, P., Bártková, J., Eerola, H., Syrjäkoski, K., Ojala, S., Kilpivaara, O., Tamminen, A., Kononen, J., Aittomäki, K., Heikkilä, P., et al. (2002) · The American Journal of Human Genetics · doi:10.1086/341943 · Cited by 467 · see citing works
CHK2 kinase in the DNA damage response and beyond
Zannini, L., Delia, D., & Buscemi, G. (2014) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mju045 · Cited by 455 · see citing works
Selective induction of E2F1 in response to DNA damage, mediated by ATM-dependent phosphorylation.
Lin, W.-C., Lin, F., & Nevins, J. R. (2001) · PubMed Central · Cited by 440 · see citing works
Chk2‐deficient mice exhibit radioresistance and defective p53‐mediated transcription
Takai, H., Naka, K., Okada, Y., Watanabe, M., Harada, N., Saito, S., Anderson, C. W., Appella, E., Nakanishi, M., Suzuki, H., et al. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf506 · Cited by 435 · see citing works
De Novo Discovery of Mutated Driver Pathways in Cancer
Vandin, F., Upfal, E., & Raphael, B. J. (2011) · Lecture notes in computer science · doi:10.1007/978-3-642-20036-6_44 · Cited by 434 · see citing works
Homologous recombinational repair of DNA ensures mammalian chromosome stability
Thompson, L. H., & Schild, D. (2001) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/s0027-5107(01)00115-4 · Cited by 426 · see citing works
The FHA domain
Durocher, D., & Jackson, S. P. (2001) · FEBS Letters · doi:10.1016/s0014-5793(01)03294-x · Cited by 421 · see citing works
Requirement for Atr in phosphorylation of Chk1 and cell cycle regulation in response to DNA replication blocks and UV-damaged DNA in Xenopus egg extracts
Guo, Z., Kumagai, A., Wang, S. X., & Dunphy, W. G. (2000) · Genes & Development · doi:10.1101/gad.842500 · Cited by 417 · see citing works
Recombinational DNA repair and human disease
Thompson, L. H., & Schild, D. (2002) · Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis · doi:10.1016/s0027-5107(02)00224-5 · Cited by 417 · see citing works
Drosophila p53 Is a Structural and Functional Homolog of the Tumor Suppressor p53
Ollmann, M. M., Young, L. M., Como, C. J. D., Karim, F. D., Belvin, M. P., Robertson, S., Whittaker, K. L., Demsky, M., Fisher, W. W., Buchman, A. R., et al. (2000) · Cell · doi:10.1016/s0092-8674(00)80626-1 · Cited by 413 · see citing works
Chk2 kinase — a busy messenger
Bártek, J., Falck, J., & Lukas, J. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35103059 · Cited by 400 · see citing works
Chk2 Is a Tumor Suppressor That Regulates Apoptosis in both an Ataxia Telangiectasia Mutated (ATM)-Dependent and an ATM-Independent Manner
Hirao, A., Cheung, A., Duncan, G. S., Girard, P.-M., Elia, A., Wakeham, A. C., Okada, H., Sarkissian, T., Wong, J. A., Sakai, T., et al. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.18.6521-6532.2002 · Cited by 404 · see citing works
Threonine 68 phosphorylation by ataxia telangiectasia mutated is required for efficient activation of Chk2 in response to ionizing radiation.
Ahn, J. Y., Schwarz, J. K., Piwnica-Worms, H. M., & Canman, C. E. (2000) · PubMed · Cited by 396 · see citing works
COP9 signalosome‐specific phosphorylation targets p53 to degradation by the ubiquitin system
Bech‐Otschir, D., Kraft, R., Huang, X., Henklein, P., Kapelari, B., Pollmann, C., & Dubiel, W. (2001) · The EMBO Journal · doi:10.1093/emboj/20.7.1630 · Cited by 396 · see citing works
Targeting the checkpoint kinases: chemosensitization versus chemoprotection
Zhou, B. S., & Bártek, J. (2004) · Nature reviews. Cancer · doi:10.1038/nrc1296 · Cited by 390 · see citing works
Cell cycle checkpoints and their inactivation in human cancer
Molinari, M. (2000) · Cell Proliferation · doi:10.1046/j.1365-2184.2000.00191.x · Cited by 389 · see citing works
Chk2 activates E2F-1 in response to DNA damage
Stevens, C., Smith, L. M., & Thangue, N. B. L. (2003) · Nature Cell Biology · doi:10.1038/ncb974 · Cited by 386 · see citing works
A p53 Amino-Terminal Nuclear Export Signal Inhibited by DNA Damage-Induced Phosphorylation
Zhang, Y., & Xiong, Y. (2001) · Science · doi:10.1126/science.1058637 · Cited by 378 · see citing works
Phosphorylation and rapid relocalization of 53BP1 to nuclear foci upon DNA damage
Anderson, L., Henderson, C., & Adachi, Y. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.5.1719-1729.2001 · Cited by 367 · see citing works
SIRT1 Regulates Apoptosis and Nanog Expression in Mouse Embryonic Stem Cells by Controlling p53 Subcellular Localization
Han, M., Song, E.-K., Guo, Y., Ou, X., Mantel, C., & Broxmeyer, H. E. (2008) · Cell stem cell · doi:10.1016/j.stem.2008.01.002 · Cited by 368 · see citing works
p53 Acetylation: Regulation and Consequences
Reed, S. M., & Quelle, D. E. (2014) · Cancers · doi:10.3390/cancers7010030 · Cited by 330 · see citing works
A role for p53 in base excision repair
Zhou, J., Ahn, J., Wilson, S. H., & Prives, C. (2001) · The EMBO Journal · doi:10.1093/emboj/20.4.914 · Cited by 333 · see citing works
MDC1 is coupled to activated CHK2 in mammalian DNA damage response pathways
Lou, Z., Minter‐Dykhouse, K., Wu, X., & Chen, J. (2003) · Nature · doi:10.1038/nature01447 · Cited by 328 · see citing works
Regulation of p53 Function
Woods, D. B., & Vousden, K. H. (2001) · Experimental Cell Research · doi:10.1006/excr.2000.5141 · Cited by 318 · see citing works
Drosophila melanogaster MNK/Chk2 and p53 Regulate Multiple DNA Repair and Apoptotic Pathways following DNA Damage
Brodsky, M. H., Weinert, B. T., Tsang, G., Rong, Y. S., McGinnis, N., Golic, K. G., Rio, D. C., & Rubin, G. M. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.3.1219-1231.2004 · Cited by 310 · see citing works
Activation and activities of the p53 tumour suppressor protein
Bálint, É., & Vousden, K. H. (2001) · British Journal of Cancer · doi:10.1054/bjoc.2001.2128 · Cited by 310 · see citing works
Threonine 68 is required for radiation-induced phosphorylation and activation of Cds1
Melchionna, R., Chen, X., Blasina, A., & McGowan, C. H. (2000) · Nature Cell Biology · doi:10.1038/35036406 · Cited by 307 · see citing works
ATM Mediates Phosphorylation at Multiple p53 Sites, Including Ser46, in Response to Ionizing Radiation
Saito, S., Goodarzi, A. A., Higashimoto, Y., Noda, Y., Lees‐Miller, S. P., Appella, E., & Anderson, C. W. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.c200093200 · Cited by 302 · see citing works
ATM: Genome stability, neuronal development, and cancer cross paths
(2001) · Advances in Cancer Research · doi:10.1016/s0065-230x(01)83007-4 · Cited by 299 · see citing works
The evolution of diverse biological responses to DNA damage: insights from yeast and p53
Wahl, G. M., & Carr, A. M. (2001) · Nature Cell Biology · doi:10.1038/ncb1201-e277 · Cited by 376 · see citing works
Damage Tolerance Protein Mus81 Associates with the FHA1 Domain of Checkpoint Kinase Cds1
Boddy, M. N., Lopez‐Girona, A., Shanahan, P., Interthal, H., Heyer, W., & Russell, P. R. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.23.8758-8766.2000 · Cited by 287 · see citing works
CHK2 kinase: cancer susceptibility and cancer therapy – two sides of the same coin?
Antoni, L., Sodha, N., Collins, I., & Garrett, M. D. (2007) · Nature reviews. Cancer · doi:10.1038/nrc2251 · Cited by 287 · see citing works
The Wip1 Phosphatase Acts as a Gatekeeper in the p53-Mdm2 Autoregulatory Loop
Lu, X., Ma, O., Nguyen, T., Jones, S. N., Oren, M., & Donehower, L. A. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.08.033 · Cited by 282 · see citing works
Multiple roles of the tumor suppressor p53
Bargonetti, J., & Manfredi, J. J. (2002) · Current Opinion in Oncology · doi:10.1097/00001622-200201000-00015 · Cited by 332 · see citing works
ATM, ATR and DNA-PK: initiators of the cellular genotoxic stress responses
Yang, H. J. (2003) · Carcinogenesis · doi:10.1093/carcin/bgg137 · Cited by 275 · see citing works
ATM and Chk2-dependent phosphorylation of MDMX contribute to p53 activation after DNA damage
Chen, L., Gilkes, D. M., Pan, Y., Lane, W. S., & Chen, J. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600812 · Cited by 260 · see citing works
Ubiquitin Ligases and Cell Cycle Control
Teixeira, L. K., & Reed, S. I. (2013) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060410-105307 · Cited by 253 · see citing works
ATM, a central controller of cellular responses to DNA damage
Khanna, K. K., Lavin, M. F., Jackson, S. P., & Mulhern, T. D. (2001) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4400874 · Cited by 251 · see citing works
Mechanism of p53 stabilization by ATM after DNA damage
Cheng, Q., & Chen, J. (2010) · Cell Cycle · doi:10.4161/cc.9.3.10556 · Cited by 248 · see citing works
Chk2 Mediates Stabilization of the FoxM1 Transcription Factor To Stimulate Expression of DNA Repair Genes
Tan, Y., Raychaudhuri, P., & Costa, R. H. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.01068-06 · Cited by 245 · see citing works
p38 Mitogen-Activated Protein Kinase- and HuR-Dependent Stabilization of p21 Cip1 mRNA Mediates the G 1 /S Checkpoint
Lafarga, V., Cuadrado, A., de Silanes, I. L., Bengoechea, R., Fernández-Capetillo, Ó., & Nebreda, Á. R. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00210-09 · Cited by 242 · see citing works
The Chk2 protein kinase
Ahn, J., Urist, M. J., & Prives, C. L. (2004) · DNA repair · doi:10.1016/j.dnarep.2004.03.033 · Cited by 240 · see citing works
PML-dependent apoptosis after DNA damage is regulated by the checkpoint kinase hCds1/Chk2
Yang, S., Kuo, C. S., Bisi, J., & Kim, M. K. (2002) · Nature Cell Biology · doi:10.1038/ncb869 · Cited by 238 · see citing works
Cellular Senescence: Molecular Mechanisms, In Vivo Significance, and Redox Considerations
Müller, M. K. (2008) · Antioxidants and Redox Signaling · doi:10.1089/ars.2008.2104 · Cited by 237 · see citing works
p73 induction after DNA damage is regulated by checkpoint kinases Chk1 and Chk2Preprint
Urist, M. J., Tanaka, T., Poyurovsky, M. V., & Prives, C. L. (2004) · Genes & Development · doi:10.1101/gad.1221004 · Cited by 234 · see citing works
Structural and Functional Versatility of the FHA Domain in DNA-Damage Signaling by the Tumor Suppressor Kinase Chk2
Li, J., Williams, B. L., Haire, L. F., Goldberg, M., Wilker, E., Durocher, D., Yaffe, M. B., Jackson, S. P., & Smerdon, S. J. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00527-0 · Cited by 229 · see citing works
p53-Mdm2--the affair that never ends
Alarcon-Vargas, D. (2002) · Carcinogenesis · doi:10.1093/carcin/23.4.541 · Cited by 231 · see citing works
Rad9 Phosphorylation Sites Couple Rad53 to the Saccharomyces cerevisiae DNA Damage Checkpoint
Schwartz, M. F., Duong, J., Sun, Z., Morrow, J. S., Pradhan, D., & Stern, D. F. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00532-4 · Cited by 228 · see citing works
Plk3 Functionally Links DNA Damage to Cell Cycle Arrest and Apoptosis at Least in Part via the p53 Pathway
Xie, S., Wu, H., Wang, Q., Cogswell, J. P., Husain, I., Conn, C. W., Stambrook, P. J., Jhanwar‐Uniyal, M., & Dai, W. H. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m106050200 · Cited by 226 · see citing works
Cellular Responses to DNA Damage: One Signal, Multiple Choices
Su, T. T. (2006) · Annual Review of Genetics · doi:10.1146/annurev.genet.40.110405.090428 · Cited by 227 · see citing works
The effects of wild-type p53 tumor suppressor activity and mutant p53 gain-of-function on cell growth
Cadwell, C., & Zambetti, G. P. (2001) · Gene · doi:10.1016/s0378-1119(01)00696-5 · Cited by 225 · see citing works
Rereplication by Depletion of Geminin Is Seen Regardless of p53 Status and Activates a G2/M Checkpoint
Zhu, W., Chen, Y., & Dutta, A. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.16.7140-7150.2004 · Cited by 222 · see citing works
Dial 9-1-1 for p53: Mechanisms of p53 Activation by Cellular Stress
Ljungman, M. E. (2000) · Neoplasia · doi:10.1038/sj.neo.7900073 · Cited by 218 · see citing works
Chk1 and Cds1: linchpins of the DNA damage and replication checkpoint pathways
Rhind, N., & Russell, P. R. (2000) · Journal of Cell Science · doi:10.1242/jcs.113.22.3889 · Cited by 217 · see citing works
The role of p53 and pRB in apoptosis and cancer
Hickman, E. S. (2002) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(01)00265-9 · Cited by 214 · see citing works

Role of Human Cds1 (Chk2) Kinase in DNA Damage Checkpoint and Its Regulation by p53
Tominaga, K., Morisaki, H., Kaneko, Y. S., Fujimoto, A., Tanaka, T., Ohtsubo, M., Hirai, M., Okayama, H., Ikeda, K., & Nakanishi, M. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.44.31463 · Cited by 100 · see citing works
Questioning the Role of Checkpoint Kinase 2 in the p53 DNA Damage Response
Ahn, J., Urist, M., & Prives, C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m213185200 · Cited by 99 · see citing works
The human homologs of checkpoint kinases Chk1 and Cds1 (Chk2) phosphorylate p53 at multiple DNA damage-inducible sites.
Shieh, S.-Y., Ahn, J., Tamai, K., Taya, Y., & Prives, C. (2000) · Genes & Development · doi:10.1101/gad.14.3.289 · Cited by 972 · see citing works
DNA Damage-Induced Activation of p53 by the Checkpoint Kinase Chk2
Hirao, A., Kong, Y., Matsuoka, S., Wakeham, A. C., Ruland, J., Yoshida, H., Liu, D., Elledge, S. J., & Mak, T. W. (2000) · Science · doi:10.1126/science.287.5459.1824 · Cited by 1,288 · see citing works
Conservation of the Chk1 Checkpoint Pathway in Mammals: Linkage of DNA Damage to Cdk Regulation Through Cdc25
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 · see citing works

Authors: Chehab, N. H., Malikzay, A., Appel, M., & Halazonetis, T. D.
Affiliations: The Wistar Institute (US)
ORCID: Halazonetis, Thanos D.
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
DOI: 10.1101/gad.14.3.278
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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Chk2/hCds1 functions as a DNA damage checkpoint in G1by stabilizing p53

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