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The role of Cdc25 phosphatases in cell cycle checkpoints

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Summary

The major driving forces in the eukaryotic cell cycle are the cyclin-dependent kinases (Cdk). Cdks can be activated through dephosphorylation of inhibitory phosphorylations catalyzed by the Cdc25 phosphatase family. In higher-eukaryotic cells, there exist three Cdc25 family members, Cdc25A, Cdc25B, and Cdc25C. While Cdc25A plays a major role at the G1-to-S phase transition, Cdc25B and C are required for entry into mitosis. The regulation of Cdc25C is crucial for the operation of the DNA-damage checkpoint. Two protein kinases, Chk1 and Cds1, can be activated in response to DNA damage or in the presence of unreplicated DNA. Chk1 and Cds1 may phosphorylate Cdc25C to prevent entry into mitosis through inhibition of Cdc2 (Cdk1) dephosphorylation.

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References

  • Amon A, Surana U, Muroff I, Nasmyth K (1992) Regulation of p34CDC28 tyrosine phosphorylation is not required for entry into mitosis in S. cerevisiae. Nature 355: 368–371

    PubMed  Google Scholar 

  • Blasina A, Van de Weyer I, Laus M, Luyten WAP, McGowan C (1999) A human homologue of the checkpoint kinase Cds1 directly inhibits Cdc25 phosphatase. Curr Biol 9: 1–10

    PubMed  Google Scholar 

  • Blomberg I, Hoffmann I (1999) Ectopic expression of Cdc25A accelerates the G1/S transition and leads to premature activation of cyclin E- and cyclin A-dependent kinases. Mol Cell Biol 19: 6183–6194

    PubMed  Google Scholar 

  • Boddy M, Funari B, Mondesert O, Russell P (1998) Replication checkpoint enforced by kinases Cds1 and Chk1. Science 280: 909–912

    PubMed  Google Scholar 

  • Enoch T, Nurse P (1991) Coupling M phase and S phase: controls maintaining the dependence of mitosis on chromosome replication. Cell 65: 921–923

    PubMed  Google Scholar 

  • Fauman E, Cogswell J, Lovejoy B, Rocque W, Holmes W, Montana V, Piwnica-Worms H, Rink M, Saper M (1998) Crystal structure of the catalytic domain of the human cell cycle control phosphatase, Cdc25A. Cell 93: 617–625

    PubMed  Google Scholar 

  • Funari B, Rhind N, Russell P (1997) Cdc25 mitotic inducer targeted by Chk1 DNA damage checkpoint kinase. Science 277: 1495–1497

    PubMed  Google Scholar 

  • Gabrielli B, DeSouza C, Tonks I, Clark J, Hayward N, Ellem K (1996) Cytoplasmic accumulation of cdc25B phosphatase in mitosis triggers centrosomal microtubule nucleation in HeLa cells. J Cell Sci 109: 1081–1093

    PubMed  Google Scholar 

  • Galaktionov K, Beach D (1991) Specific activation of cdc25 tyrosine phosphatase by B-type cyclins: evidence for multiple roles of mitotic cyclins. Cell 67: 1181–1194

    PubMed  Google Scholar 

  • —, Lee A, Eckstein J, Draetta G, Meckler J, Loda M, Beach D (1995) Cdc25 phosphatases as potential human oncogenes. Science 269: 1575–1577

    PubMed  Google Scholar 

  • Gasparotto D, Maestro R, Piccinin S, Vukosavljevic T, Barzan L, Sulfaro S, Boiocchi M (1997) Overexpression of Cdc25A and Cdc25B in head and neck cancers. Cancer Res 57: 2366–2368

    PubMed  Google Scholar 

  • Harper W, Elledge S (1998) The role of Cdk7 in CAK function, a retro-retrospective. Genes Dev 12: 285–289

    PubMed  Google Scholar 

  • Hernandez S, Hernandez I, Bea S, Cazorla M, Fernandez P, Nadal A, Muntane J, Mallofre C, Montserrat E, Cardesa A, Campo E (1998) Cdc25 cell cycle-activating phosphatases and c-myc expression in human non-Hodgkin's lymphomas. Cancer Res 58: 1762–1767

    PubMed  Google Scholar 

  • Hoffmann I, Clarke PR, Marcote MJ, Karsenti E, Draetta G (1993) Phosphorylation and activation of human cdc25C by Cdc2/cyclin B and its involvement in the self-amplification of MPF at mitosis. EMBO J 12: 53–63

    PubMed  Google Scholar 

  • —, Draetta G, Karsenti E (1994) The tyrosine phosphatase activity of human cdc25A is activated by cyclin E/cdk2 during the G1/S transition. EMBO J 13: 4302–4310

    PubMed  Google Scholar 

  • Izumi T, Maller J (1993) Elimination of cdc2 phosphorylation sites in the cdc25 phosphatase blocks initiation of M-phase. Mol Biol Cell 4: 1337–1350

    PubMed  Google Scholar 

  • Jinno S, Suto K, Nagata A, Igarashi M, Kanaoka Y, Nojima H, Okayama H (1994) Cdc25A is a novel phosphatase functioning early in the cell cycle. EMBO J 13: 1549–1556

    PubMed  Google Scholar 

  • Kumagai A, Dunphy WG (1992) Regulation of the cdc25 protein during the cell cycle inXenopus extracts. Cell 70: 139–151

    PubMed  Google Scholar 

  • — — (1996) Purification and molecular cloning of Plx1, a cdc25-stimulatory kinase fromXenopus egg extracts. Science 273: 1377–1380

    PubMed  Google Scholar 

  • —, Guo Z, Emami K, Wang S, Dunphy W (1998) TheXenopus Chk1 protein kinase mediates a caffeine-sensitive pathway of checkpoint controls in cell-free extracts. J Cell Biol 142: 1559–1569

    PubMed  Google Scholar 

  • Lammer C, Wagerer S, Saffrich R, Mertens D, Ansorge W, Hoffmann I (1998) The cdc25B phosphatase is essential for the G2/M phase transition in human cells. J Cell Sci 111: 2445–2453

    PubMed  Google Scholar 

  • Lew D, Kornbluth S (1996) Regulatory roles of cyclin dependent kinase phosphorylation in cell cycle control. Curr Opin Cell Biol 8: 795–804

    PubMed  Google Scholar 

  • —, Reed S (1995) A cell cycle checkpoint monitors cell morphogenesis in budding yeast. J Cell Biol 129: 739–749

    PubMed  Google Scholar 

  • Lopez-Girona A, Funari B, Mondesert O, Russell P (1999) Nuclear localization of Cdc25 is regulated by DNA damage and a 14-3-3 protein. Nature 397: 172–175

    PubMed  Google Scholar 

  • Matsuoka S, Huang M, Elledge S (1998) Linkage of ATM to cell cycle regulation by the Chk2 protein kinase. Science 282: 1893–1896

    PubMed  Google Scholar 

  • Millar JBA, Blevitt J, Gerace L, Sadhu K, Featherstone C, Russell P (1991) p55cdc25 is a nuclear protein required for initiation of mitosis in human cells. Proc Natl Acad Sci USA 88: 10500–10504

    PubMed  Google Scholar 

  • Morgan D (1995) Principles of cdk regulation. Nature 374: 131–134

    PubMed  Google Scholar 

  • Nagata A, Igarashi M, Jinno S, Suto K, Okayama H (1991) An additional homolog of the fission yeast cdc25 gene occurs in humans and is highly expressed in some cancer cells. New Biol 3: 959–967

    PubMed  Google Scholar 

  • Nishijima H, Nishitani H, Seki T, Nishimoto T (1997) A dualspecificity phosphatase cdc25B is an unstable protein and triggers p34cdc2/cyclinB activation in hamster BHK21 cells arrested with hydroxyurea. J Cell Biol 138: 1105–1116

    PubMed  Google Scholar 

  • Peng C, Graves P, Thoma R, Wu R, Shaw A, Piwnica-Worms H (1997) Mitotic and G2 checkpoint control: regulation of 14-3-3 protein binding by phosphorylation of cdc25C on serine-216. Science 277: 1501–1505

    PubMed  Google Scholar 

  • Rhind N, Russell P (1998) Tyrosine phosphorylation of Cdc2 is required for the replication checkpoint inSchizosaccharomyces pombe. Mol Cell Biol 18: 3782–3787

    PubMed  Google Scholar 

  • —, Furnari B, Russell P (1997) Cdc2 tyrosine phosphorylation is required for the DNA damage checkpouint in fission yeast. Genes Dev 11: 504–511

    PubMed  Google Scholar 

  • Sadhu K, Reed SI, Richardson H, Russell P (1990) Human homolog of fission yeastcdc25 is predominantly expressed in G1. Proc Natl Acad Sci USA 87: 5139–5143

    PubMed  Google Scholar 

  • Sanchez Y, Wong C, Thoma R, Richman R, Wu Z, Piwnica-Worms H, Elledge S (1997) Conservation of the chk1 checkpoint pathway in mammals: linkage of DNA damage to cdk regulation through cdc25. Science 277: 1497–1501

    PubMed  Google Scholar 

  • Sorger P, Murray A (1992) S-phase feedback control in budding yeast independent of tyrosine phosphorylation of p34cdc28. Nature 355: 365–368

    PubMed  Google Scholar 

  • Walworth N, Davey S, Beach D (1993) Fission yeast chkl protein kinase links the rad checkpoint pathway to cdc2. Nature 363: 368–371

    PubMed  Google Scholar 

  • Wu W, Fan Y, Kemp B, Walsh G, Mao L (1998) Overexpression of Cdc25A and Cdc25B is frequent in primary non-small cell lung cancer but is not associated with overexpression of c-myc. Cancer Res 58: 4082–4085

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Angewandte Tumorvirologie (F0400), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 242, D-69120, Heidelberg, Federal Republic of Germany

    Ingrid Hoffmann

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  1. Ingrid Hoffmann
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Hoffmann, I. The role of Cdc25 phosphatases in cell cycle checkpoints. Protoplasma 211, 8–11 (2000). https://doi.org/10.1007/BF01279894

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  • DOI: https://doi.org/10.1007/BF01279894

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