Conservation of the Chk1 Checkpoint Pathway in Mammals: Linkage of DNA Damage to Cdk Regulation Through Cdc25
Abstract
In response to DNA damage, mammalian cells prevent cell cycle progression through the control of critical cell cycle regulators. A human gene was identified that encodes the protein Chk1, a homolog of the Schizosaccharomyces pombe Chk1 protein kinase, which is required for the DNA damage checkpoint. Human Chk1 protein was modified in response to DNA damage. In vitro Chk1 bound to and phosphorylated the dual-specificity protein phosphatases Cdc25A, Cdc25B, and Cdc25C, which control cell cycle transitions by dephosphorylating cyclin-dependent kinases. Chk1 phosphorylates Cdc25C on serine-216. As shown in an accompanying paper by Peng et al . in this issue, serine-216 phosphorylation creates a binding site for 14-3-3 protein and inhibits function of the phosphatase. These results suggest a model whereby in response to DNA damage, Chk1 phosphorylates and inhibits Cdc25C, thus preventing activation of the Cdc2–cyclin B complex and mitotic entry.
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Chk1 phosphorylation increases its kinase activity, allowing it to phosphorylate substrates such as Cdc25, BLM, and FANCD2/FANCE and to promote cell cycle arrest and DNA repair.
“The phosphorylation of Chk1 enhances Chk1’s kinase activity, which in turn phosphorylates downstream substrates (e.g., Cdc25, BLM, and FANCD2/FANCE) and facilitates cell cycle arrest and DNA damage repair [91–93].”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [91]
Cites
Kozak, M. (1986) · Cell · doi:10.1016/0092-8674(86)90762-2 · Cited by 4,741 · see citing works
Mice Lacking p21CIP1/WAF1 undergo normal development, but are defective in G1 checkpoint control
Deng, C., Zhang, P., Wade Harper, J., Elledge, S. J., & Leder, P. (1995) · Cell · doi:10.1016/0092-8674(95)90039-x · Cited by 2,113 · see citing works
Self-citationCell 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
Self-citationPeng, 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 · see citing works
Self-citationRadiation-induced cell cycle arrest compromised by p21 deficiency
Brugarolas, J., Chandrasekaran, C., Gordon, J. I., Beach, D., Jacks, T., & Hannon, G. J. (1995) · Nature · doi:10.1038/377552a0 · Cited by 1,242 · see citing works
Wodarz, A., Hinz, U., Engelbert, M., & Knust, E. (1995) · Cell · doi:10.1016/0092-8674(95)90053-5 · Cited by 661 · see citing works
Enoch, T., & Nurse, P. (1990) · Cell · doi:10.1016/0092-8674(90)90669-6 · Cited by 460 · see citing works
Fission yeast chkl protein kinase links the rad checkpoint pathway to cdc2
Walworth, N. C., Davey, S. K., & Beach, D. (1993) · Nature · doi:10.1038/363368a0 · Cited by 452 · see citing works
Chk1 is a wee1 kinase in the G2 DNA damage checkpoint inhibiting cdc2 by Y15 phosphorylation
O’Connell, M. J., Raleigh, J., Verkade, H. M., & Nurse, P. (1997) · The EMBO Journal · doi:10.1093/emboj/16.3.545 · Cited by 398 · 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
Al-Khodairy, F. M., Fotou, E., Sheldrick, K. S., Griffiths, D. J. F., Lehmann, A. R., & Carr, A. M. (1994) · Molecular Biology of the Cell · doi:10.1091/mbc.5.2.147 · Cited by 341 · see citing works
Regulatory roles of cyclin dependent kinase phosphorylation in cell cycle control
Lew, D. J., & Kornbluth, S. A. (1996) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(96)80080-9 · Cited by 340 · see citing works
DNA-replication checkpoint control at the Drosophila midblastula transition
Sibon, O. C. M., Stevenson, V. A., & Theurkauf, W. E. (1997) · Nature · doi:10.1038/40439 · Cited by 258 · see citing works
Cdc2 tyrosine phosphorylation is required for the DNA damage checkpoint in fission yeast.Preprint
Rhind, N., Furnari, B. A., & Russell, P. R. (1997) · Genes & Development · doi:10.1101/gad.11.4.504 · Cited by 256 · see citing works
Role of inhibitory CDC2 phosphorylation in radiation-induced G2 arrest in human cells.
Jin, P., Gu, Y., & Morgan, D. O. (1996) · The Journal of Cell Biology · doi:10.1083/jcb.134.4.963 · Cited by 250 · see citing works
Fogarty, P. F., Campbell, S. D., Abu-Shumays, R. L., Phalle, B. D. S., Yu, K. R., Uy, G. L., Goldberg, M. L., & Sullivan, W. (1997) · Current Biology · doi:10.1016/s0960-9822(06)00189-8 · Cited by 208 · see citing works
Identification of phosphorylated sites in the mouse glucocorticoid receptor.
Bodwell, J. E., Ortí, E., Coull, J., Pappin, D., Smith, L. I., & Swift, F. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(20)89482-4 · Cited by 201 · see citing works
Requirement for tyrosine phosphorylation of Cdk4 in Gl arrest induced by ultraviolet irradiation
Terada, Y., Tatsuka, M., Jinno, S., & Okayama, H. (1995) · Nature · doi:10.1038/376358a0 · Cited by 187 · see citing works
Analysis of the ATM protein in wild-type and ataxia telangiectasia cells.
Lakin, N. D., Weber, P., Stanković, T., Rottinghaus, S. T., Taylor, A. M. R., & Jackson, S. P. (1996) · PubMed · Cited by 148 · see citing works
Vořechovský, I., Rasio, D., Luo, L., Monaco, C., Hammarström, L. L. G., WEBSTER, A. D. B., Žaloudík, J., Barbanti-Brodani, G., James, M. R., & Russo, G. (1996) · PubMed · Cited by 147 · see citing works
The Product of the ATM Gene Is a 370-kDa Nuclear Phosphoprotein
Chen, G., & Lee, E. Y.-H. P. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.52.33693 · Cited by 129 · see citing works
Purification of a serine kinase that associates with and phosphorylates human Cdc25C on serine 216.
Ogg, S., Gabrielli, B. G., & Piwnica-Worms, H. M. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)43836-7 · Cited by 100 · see citing works
Self-citationA manual sequencing method for identification of phosphorylated amino acids in phosphopeptides
Sullivan, S., & Wong, T. W. (1991) · Analytical Biochemistry · doi:10.1016/0003-2697(91)90356-x · Cited by 87 · see citing works
Kholodnyuk, I., Kost‐Alimova, M., Kashuba, V. I., Gizatullin, R. Z., Szeles, A., Stanbridge, E. J., Zabarovsky, E. R., Klein, G., & Imreh, S. (1997) · Genes Chromosomes and Cancer · doi:10.1002/(sici)1098-2264(199703)18:3 · Cited by 39 · see citing works
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Cellular processing of platinum anticancer drugs
Wang, D., & Lippard, S. J. (2005) · Nature Reviews Drug Discovery · doi:10.1038/nrd1691 · Cited by 3,801 · see citing works
Molecular Mechanisms of Mammalian DNA Repair and the DNA Damage Checkpoints
Sancar, A., Lindsey-Boltz, L. A., Ünsal-Kaçmaz, K., & Linn, S. (2004) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.73.011303.073723 · Cited by 3,317 · 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
Self-citationDNA double-strand breaks: signaling, repair and the cancer connection
Khanna, K. K., & Jackson, S. P. (2001) · Nature Genetics · doi:10.1038/85798 · Cited by 2,455 · 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
Cell cycle proteins as promising targets in cancer therapy
Otto, T., & Siciński, P. (2017) · Nature reviews. Cancer · doi:10.1038/nrc.2016.138 · Cited by 1,873 · see citing works
ATR: an essential regulator of genome integrity
Cimprich, K. A., & Cortez, D. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2450 · Cited by 1,798 · see citing works
The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer
Vermeulen, K., Bockstaele, D. R. V., & Berneman, Z. N. (2003) · Cell Proliferation · doi:10.1046/j.1365-2184.2003.00266.x · Cited by 1,766 · see citing works
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
Self-citation14-3-3 Proteins: Structure, Function, and Regulation
Fu, H., Subramanian, R. R., & Masters, S. C. (2000) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.40.1.617 · Cited by 1,569 · see citing works
Regulation of the G2/M transition by p53
Taylor, W. R., & Stark, G. R. (2001) · Oncogene · doi:10.1038/sj.onc.1204252 · Cited by 1,553 · see citing works
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 · see citing works
Self-citationDNA 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
Self-citationIs a p53-Regulated Inhibitor of G2/M Progression
Hermeking, H., Lengauer, C., Polyak, K., He, T.-C., Zhang, L., Thiagalingam, S., Kinzler, K. W., & Vogelstein, B. (1997) · Molecular Cell · doi:10.1016/s1097-2765(00)80002-7 · Cited by 1,251 · see citing works
ATR-Mediated Checkpoint Pathways Regulate Phosphorylation and Activation of Human Chk1
Zhao, H., & Piwnica-Worms, H. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.13.4129-4139.2001 · Cited by 1,091 · see citing works
Self-citationThe 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
(1999) · PubMed · Cited by 1,030 · see citing works
DNA interstrand crosslink repair and cancer
Deans, A. J., & West, S. C. (2011) · Nature reviews. Cancer · doi:10.1038/nrc3088 · Cited by 1,019 · see citing works
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
Targeting DNA damage response pathways in cancer
Groelly, F. J., Fawkes, M., Dagg, R. A., Blackford, A. N., & Tarsounas, M. (2022) · Nature reviews. Cancer · doi:10.1038/s41568-022-00535-5 · Cited by 868 · 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
Self-citationThe essential kinase ATR: ensuring faithful duplication of a challenging genome
Saldivar, J. C., Cortez, D., & Cimprich, K. A. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.67 · Cited by 829 · see citing works
Chk2/hCds1 functions as a DNA damage checkpoint in G<sub>1</sub>by stabilizing p53
Chehab, N. H., Malikzay, A., Appel, M., & Halazonetis, T. D. (2000) · Genes & Development · doi:10.1101/gad.14.3.278 · Cited by 805 · see citing works
Rapid Destruction of Human Cdc25A in Response to DNA Damage
Mailand, N., Falck, J., Lukas, C., Syljuåsen, R. G., Welcker, M., Bartek, J., & Lukas, J. (2000) · Science · doi:10.1126/science.288.5470.1425 · Cited by 787 · 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
CDC25 phosphatases in cancer cells: key players? Good targets?
Boutros, R., Lobjois, V., & Ducommun, B. (2007) · Nature reviews. Cancer · doi:10.1038/nrc2169 · Cited by 710 · see citing works
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
GADD45 induction of a G <sub>2</sub> /M cell cycle checkpoint
Wang, X. W., Zhan, Q., Coursen, J. D., Khan, M. A., Kontny, H. U., Yu, L., Hollander, M. C., O’Connor, P. M., Fornace, A. J., & Harris, C. C. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.7.3706 · Cited by 634 · 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
Nuclear localization of Cdc25 is regulated by DNA damage and a 14-3-3 protein
Lopez‐Girona, A., Furnari, B. A., Mondésert, O., & Russell, P. R. (1999) · Nature · doi:10.1038/16488 · Cited by 574 · see citing works
Sørensen, C. S., Syljuåsen, R. G., Falck, J., Schroeder, T., Rönnstrand, L., Khanna, K. K., Zhou, B.-B., Bártek, J., & Lukas, J. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00048-5 · Cited by 560 · see citing works
Molecular Interaction Map of the Mammalian Cell Cycle Control and DNA Repair Systems
Kohn, K. W. (1999) · Molecular Biology of the Cell · doi:10.1091/mbc.10.8.2703 · Cited by 550 · see citing works
Syljuåsen, R. G., Sørensen, C. S., Hansen, L. T., Fugger, K., Lundin, C., Johansson, F., Helleday, T., Sehested, M., Lukas, J., & Bártek, J. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.9.3553-3562.2005 · Cited by 550 · see citing works
Gasch, A. P., Huang, M., Metzner, S., Botstein, D., Elledge, S. J., & Brown, P. O. (2001) · Molecular Biology of the Cell · doi:10.1091/mbc.12.10.2987 · Cited by 542 · see citing works
Self-citationGraves, P. R., Yu, L., Schwarz, J. K., Gales, J., Sausville, E. A., O'Connor, P. M., & Piwnica-Worms, H. M. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.8.5600 · Cited by 540 · see citing works
Self-citation14‐3‐3 proteins: key regulators of cell division, signalling and apoptosis
van Hemert, M. J., Steensma, H. Y., & van Heusden, G. P. H. (2001) · BioEssays · doi:10.1002/bies.1134 · Cited by 535 · see citing works
Initiation of a G2/M checkpoint after ultraviolet radiation requires p38 kinase
Bulavin, D. V., Higashimoto, Y., Popoff, I., Gaarde, W. A., Basrur, V., Potapova, O., Appella, E., & Fornace, A. J. (2001) · Nature · doi:10.1038/35075107 · Cited by 531 · see citing works
Shackelford, R. E., Kaufmann, W. K., & Paules, R. S. (2000) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(00)00224-0 · Cited by 520 · see citing works
Essential and dispensable roles of ATR in cell cycle arrest and genome maintenance
Brown, E. J., & Baltimore, D. (2003) · Genes & Development · doi:10.1101/gad.1067403 · Cited by 511 · see citing works
Huang, M., Zhou, Z., & Elledge, S. J. (1998) · Cell · doi:10.1016/s0092-8674(00)81601-3 · Cited by 499 · see citing works
Self-citationFei, P., & El‐Deiry, W. S. (2003) · Oncogene · doi:10.1038/sj.onc.1206677 · Cited by 497 · see citing works
BRCA1 regulates the G2/M checkpoint by activating Chk1 kinase upon DNA damage
Yarden, R. I., Pardo-Reoyo, S., Sgagias, M. K., Cowan, K. H., & Brody, L. C. (2002) · Nature Genetics · doi:10.1038/ng837 · Cited by 483 · see citing works
Aberrant cell cycle checkpoint function and early embryonic death in Chk1−/− micePreprint
Takai, H., Tominaga, K., Motoyama, N., Minamishima, Y. A., Nagahama, H., Tsukiyama, T., Ikeda, K., Nakayama, K., Nakanishi, M., & Nakayama, K. (2000) · Genes & Development · doi:10.1101/gad.14.12.1439 · Cited by 478 · see citing works
DNA damage checkpoint control in cells exposed to ionizing radiation
Iliakis, G. E., Wang, Y., Guan, J., & Wang, H. (2003) · Oncogene · doi:10.1038/sj.onc.1206682 · 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
Roles of Chk1 in cell biology and cancer therapy
Zhang, Y., & Hunter, T. (2014) · International Journal of Cancer · doi:10.1002/ijc.28226 · Cited by 462 · see citing works
Zhao, H., Watkins, J. L., & Piwnica-Worms, H. M. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.182557299 · Cited by 459 · see citing works
Self-citationA unified view of the DNA-damage checkpoint
Melo, J. A., & Toczyski, D. P. (2002) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(02)00312-5 · Cited by 457 · see citing works
Dougherty, M. K., & Morrison, D. K. (2004) · Journal of Cell Science · doi:10.1242/jcs.01171 · Cited by 457 · see citing works
Recovery from DNA replicational stress is the essential function of the S-phase checkpoint pathwayPreprint
Desany, B. A., Alcasabas, A. A., Bachant, J. B., & Elledge, S. J. (1998) · Genes & Development · doi:10.1101/gad.12.18.2956 · Cited by 448 · see citing works
Self-citationCell cycle regulation by the Cdc25 phosphatase family
Nilsson, I., & Hoffmann, I. (2000) · Springer eBooks · doi:10.1007/978-1-4615-4253-7_10 · Cited by 445 · see citing works
Hallmarks of DNA replication stress
Saxena, S., & Zou, L. (2022) · Molecular Cell · doi:10.1016/j.molcel.2022.05.004 · Cited by 442 · 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
Regulating mammalian checkpoints through Cdc25 inactivation
Donzelli, M., & Draetta, G. F. (2003) · EMBO Reports · doi:10.1038/sj.embor.embor887 · Cited by 435 · see citing works
Hermeking, H. (2003) · Nature reviews. Cancer · doi:10.1038/nrc1230 · Cited by 434 · see citing works
DNA damage checkpoints in mammals
Niida, H., & Nakanishi, M. (2005) · Mutagenesis · doi:10.1093/mutage/gei063 · Cited by 431 · see citing works
Kumagai, A., & Dunphy, W. G. (2000) · Molecular Cell · doi:10.1016/s1097-2765(05)00092-4 · Cited by 430 · see citing works
Dasika, G. K., Lin, S.-C. J., Zhao, S., Sung, P., Tomkinson, A., & Lee, E. Y.-H. P. (1999) · Oncogene · doi:10.1038/sj.onc.1203283 · Cited by 427 · 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
Mammalian Chk2 is a downstream effector of the ATM-dependent DNA damage checkpoint pathway
Chaturvedi, P., Eng, W.-K., Zhu, Y., Mattern, M. R., Mishra, R., Hurle, M. R., Zhang, X., Annan, R. S., Lu, Q., Faucette, L. F., et al. (1999) · Oncogene · doi:10.1038/sj.onc.1202925 · Cited by 420 · see citing works
Guo, Z., Kumagai, A., Wang, S. X., & Dunphy, W. G. (2000) · Genes & Development · doi:10.1101/gad.842500 · Cited by 417 · see citing works
The when and wheres of CDC25 phosphatases
Boutros, R., Dozier, C., & Ducommun, B. (2006) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2006.02.003 · Cited by 417 · see citing works
Zabludoff, S., Deng, C., Grondine, M. R., Sheehy, A. M., Ashwell, S., Caleb, B. L., Green, S. A., Haye, H. R., Horn, C. L., Janetka, J. W., et al. (2008) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-08-0492 · Cited by 411 · 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
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
Control of mitosis by changes in the subcellular location of cyclin-B1–Cdk1 and Cdc25C
Takizawa, C. G., & Morgan, D. O. (2000) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(00)00149-6 · Cited by 390 · see citing works
PPM1D dephosphorylates Chk1 and p53 and abrogates cell cycle checkpoints
Lu, X., Nannenga, B., & Donehower, L. A. (2005) · Genes & Development · doi:10.1101/gad.1291305 · Cited by 389 · see citing works
Four-dimensional control of the cell cycle
Pines, J. (1999) · Nature Cell Biology · doi:10.1038/11041 · Cited by 389 · 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
Chk1 mediates S and G2 arrests through Cdc25A degradation in response to DNA-damaging agents
Xiao, Z., Chen, Z., Gunasekera, A. H., Sowin, T. J., Rosenberg, S. H., Fesik, S., & Zhang, H. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300229200 · Cited by 388 · see citing works
The G2-phase DNA-damage checkpoint
O’Connell, M. J., Walworth, N. C., & Carr, A. M. (2000) · Trends in Cell Biology · doi:10.1016/s0962-8924(00)01773-6 · Cited by 385 · see citing works
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
G2 checkpoint abrogators as anticancer drugs
Kawabe, T. (2004) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.513.3.4 · Cited by 376 · see citing works
Cell cycle checkpoint in cancer: a therapeutically targetable double-edged sword
Visconti, R., Monica, R. D., & Grieco, D. (2016) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-016-0433-9 · Cited by 364 · see citing works
Identification of chemically diverse Chk1 inhibitors by receptor-based virtual screening
Foloppe, N., Fisher, L. M., Howes, R., Potter, A. J., Robertson, A., & Surgenor, A. E. (2006) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2006.03.021 · Cited by 363 · see citing works
Thompson, L. H. (2012) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2012.06.002 · Cited by 357 · see citing works
Checking out the G2/M transition
Smits, V. A. J., & Medema, R. H. (2001) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/s0167-4781(01)00204-4 · Cited by 357 · see citing works
Phosphoserine/threonine-binding domains
Yaffe, M. B., & Elia, A. E. H. (2001) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(00)00189-7 · Cited by 350 · see citing works
Singh, S. V., Herman-Antosiewicz, A., Singh, A., Lew, K. L., Srivastava, S., Kamath, R., Brown, K. D., Zhang, L., & Rajasekaran, B. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m313538200 · Cited by 347 · see citing works
Vairapandi, M., Balliet, A. G., Hoffman‐Liebermann, B., & Liebermann, D. A. (2002) · Journal of Cellular Physiology · doi:10.1002/jcp.10140 · Cited by 343 · 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
Self-citationSCF<sup>β-TRCP</sup> links Chk1 signaling to degradation of the Cdc25A protein phosphatase
Jin, J., Shirogane, T., Xu, L., Nalepa, G., Qin, J., Elledge, S. J., & Harper, J. W. (2003) · Genes & Development · doi:10.1101/gad.1157503 · Cited by 340 · see citing works
Self-citationCentrosome-associated Chk1 prevents premature activation of cyclin-B–Cdk1 kinase
Krämer, A., Mailand, N., Lukas, C., Syljuåsen, R. G., Wilkinson, C. J., Nigg, E. A., Bártek, J., & Lukas, J. (2004) · Nature Cell Biology · doi:10.1038/ncb1165 · Cited by 338 · see citing works
Plk1 promotes nuclear translocation of human Cdc25C during prophase
Toyoshima, F., Taniguchi, E., & Nishida, E. (2002) · EMBO Reports · doi:10.1093/embo-reports/kvf069 · Cited by 338 · see citing works
MPF localization is controlled by nuclear export
Hagting, A., Karlsson, C., Clute, P., Jackman, M. R., & Pines, J. (1998) · The EMBO Journal · doi:10.1093/emboj/17.14.4127 · Cited by 333 · see citing works
Forced Mitotic Entry of S-Phase Cells as a Therapeutic Strategy Induced by Inhibition of WEE1
Aarts, M., Sharpe, R., García-Murillas, I., Gevensleben, H., Hurd, M. S., Shumway, S. D., Toniatti, C., Ashworth, A., & Turner, N. C. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-11-0320 · Cited by 327 · see citing works
Lecona, E., & Fernández-Capetillo, Ó. (2018) · Nature reviews. Cancer · doi:10.1038/s41568-018-0034-3 · Cited by 327 · see citing works
Activation of mammalian Chk1 during DNA replication arrest
Feijóo, C. G., Hall-Jackson, C. A., Wu, R., Jenkins, D., Leitch, J., Gilbert, D. M., & Smythe, C. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.200104099 · Cited by 318 · see citing works
Checkpoint kinase 1 in DNA damage response and cell cycle regulation
Patil, M., Pabla, N., & Dong, Z. (2013) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-013-1307-3 · Cited by 317 · see citing works
Sørensen, C. S., & Syljuåsen, R. G. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr697 · Cited by 316 · see citing works
Involvement of 14‐3‐3 proteins in nuclear localization of telomerase
Seimiya, H., Sawada, H., Muramatsu, Y., Shimizu, M., Ohko, K., Yamane, K., & Tsuruo, T. (2000) · The EMBO Journal · doi:10.1093/emboj/19.11.2652 · Cited by 314 · see citing works
(2000) · PubMed · Cited by 314 · see citing works
Profiling of UV-induced ATM/ATR signaling pathways
Stokes, M. P., Rush, A. J., MacNeill, J., Ren, J. M., Sprott, K. M., Nardone, J., Yang, V., Beausoleil, S. A., Gygi, S. P., Livingstone, M., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707579104 · Cited by 313 · see citing works
Signal Transduction and Cellular Radiation Responses
Schmidt‐Ullrich, R., Dent, P., Grant, S., Mikkelsen, R. B., & Valerie, K. C. (2000) · Radiation Research · doi:10.1667/0033-7587(2000)153[0245:stacrr]2.0.co;2 · Cited by 311 · see citing works
14-3-3 proteins in cell cycle regulation
Hermeking, H., & Benzinger, A. (2006) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2006.03.002 · Cited by 307 · see citing works
Mitotic and mitogenic Wnt signalling
Niehrs, C., & Acebron, S. P. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.124 · Cited by 305 · see citing works
The cdc25B phosphatase is essential for the G 2/M phase transition in human cells
Lammer, C., Wagerer, S., Saffrich, R., Mertens, D., Ansorge, W. J., & Hoffmann, I. (1998) · Journal of Cell Science · doi:10.1242/jcs.111.16.2445 · Cited by 305 · see citing works
Kumagai, A., & Dunphy, W. G. (1999) · Genes & Development · doi:10.1101/gad.13.9.1067 · Cited by 303 · see citing works
Laronga, C., Yang, H.-Y., Neal, C. L., & Lee, M. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m905616199 · Cited by 302 · see citing works
- Authors
- Sanchez, Y., Wong, C., Thoma, R. S., Richman, R., Wu, Z., Piwnica-Worms, H., & Elledge, S. J.
- Affiliations
- Y. Sanchez, C. Wong, S. J. Elledge, Verna and Marrs McLean Department of Biochemistry, Department of Molecular and Human Genetics, Howard Hughes Medical Institute, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
- Howard Hughes Medical Institute (US)
- Venue
- Science
- Published
- 1997-09-05
- Volume
- 277
- Issue
- 5331
- Pages
- 1497-1501
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2105592350
- Cited by
- 1,320
- References
- 24
- Citations by year
- 2026: 11 · 2025: 20 · 2024: 14 · 2023: 32 · 2022: 29 · 2021: 25 · 2020: 30 · 2019: 22 · 2018: 22 · 2017: 35 · 2016: 34 · 2015: 39 · 2014: 29 · 2013: 37 · 2012: 39
- FWCI
- 30.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1f32gm017763-01)
- National Institute of General Medical Sciences (GM-44664, GM17763)
- 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, DNA damage checkpoint, Cdc25 phosphatase, cyclin-dependent kinases, cell cycle regulation, 14-3-3 protein binding, mitotic entry, protein kinases, mammalian cells
- MeSH terms
- Checkpoint Kinase 1, F-Box-WD Repeat-Containing Protein 7, Amino Acid Sequence, Animals, Chromosome Mapping, Chromosomes, Human, Pair 11, Cytoskeletal Proteins, DNA Damage, HeLa Cells, Humans, Mitosis, Molecular Sequence Data, Phosphoprotein Phosphatases, Phosphorylation, Phosphoserine, Protein Kinases, Proteins, Recombinant Fusion Proteins, Transfection, Tyrosine 3-Monooxygenase, Signal Transduction, G2 Phase, CDC2 Protein Kinase, Protein Tyrosine Phosphatases, Cell Cycle Proteins, cdc25 Phosphatases, Schizosaccharomyces pombe Proteins, Ubiquitin-Protein Ligases, F-Box Proteins, 14-3-3 Proteins, Mice
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