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Caffeine overrides the S-phase cell cycle block in sea urchin embryos

Published online by Cambridge University Press:  26 September 2008

Rajnikant Patel ,
Elizabeth M. Wright  and
Michael Whitaker
Rajnikant Patel
Affiliation:
Department of Biochemistry, University of Leicester, University Road, Leicester LE1 7RH, UK.
Elizabeth M. Wright
Affiliation:
Department of Physiological Scences, Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK
Michael Whitaker*
Affiliation:
Department of Physiological Scences, Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK
*
Michael Whitaker, Department of Physiological Sciences, Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK. Telephone: +44 (0)191 222 5475. Fax: +44 (0)191 222 6706.
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Summary

During the early mitotic cell cycles of the sea urchin embryo, the cell oscillates between S-phase and M-phase. In the presence of aphidicolin, a DNA synthesis inhibitor, a checkpoint control blocks the activation of the p34cdc2 protein kinase, by keeping it in the inactive, tyrosine phosphorylated form, and the embryos do not enter mitosis. Caffeine has been shown to bypass the G2/M-phase checkpoint in mammalian cells and in cycling Xenopus extracts and to induce mitosis despite the presence of damaged or unreplicated DNA. In this study we show that caffeine also induces mitosis and cell division in sea urchin embryos, in the presence of unreplicated DNA, by stimulating the tyrosine dephosphorylation of p34cdc2 and switching on its protein kinase activity. We also show that the caffeine-induced activation of the p34cdc2 protein kinase is not mediated by either of the two second messengers, calcium and cAMP, or by inhibition of the p34cdc2 tyrosine kinase. Thus, none of the mechanisms proposed for caffeine's action can explain how it overrides the S-phase checkpoint in the early cell cycles of the sea urchin embryo.

Keywords

AphidicolinCaffeineCell cyclep34cdc2Sea urchin
Type
Article
Information
Zygote , Volume 5 , Issue 2 , May 1997 , pp. 127 - 138
Copyright
Copyright © Cambridge University Press 1997

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References

Al-Khodairi, F. & Carr, A.M. (1992). DNA repair mutants defining G2 checkpoint pathways in Schizosacharomyces pombe. EMBO J. 11, 1343–50.CrossRefGoogle Scholar
Arion, D. & Meijer, L. (1989). M-phase-specific protein kinase from mitotic sea urchin eggs: cyclic activation depends on protein synthesis and phosphorylation but does not require DNA or RNA synthesis. Exp. Cell Res. 183, 361–75.CrossRefGoogle ScholarPubMed
Boynton, A.L., Whitfield, J.F., Isaacs, R.J. & Morton, H.J. (1974). Control of 3T3 cell proliferation by calcium. In Vitro 10, 12–17.CrossRefGoogle ScholarPubMed
Browne, C.L., Bower, W.A., Palazzo, R.E. & Rebhun, L.I. (1990). Inhibition of mitosis in fertilized sea urchin eggs by inhibition of the cyclic AMP-dependent protein kinase. Exp. Cell Res. 188, 122–8.CrossRefGoogle ScholarPubMed
Butcher, R.W. & Sutherland, E.W. (1962). Adenosine 3',5'-phosphate in biological materials. I. Purification and properties of cyclic 3',5'-nucleotide phosphodiesterase and use of this enzyme to characterize adenosine 3',5'-phosphate in human urine. J. Biol. Chem. 237, 1244–50.CrossRefGoogle Scholar
Ciapa, B., Crossley, I. & DeRenzis, G. (1988). Structural modifications induced by TPA (12-O-tetradecanoyl phorbol-13-acetate) in sea urchin eggs. Dev. Biol. 128, 142–9.CrossRefGoogle ScholarPubMed
Dasso, M. & Newport, J.W. (1990). Completion of DNA replication is monitored by a feedback system that controls the initiation of mitosis in vitro: studies in Xenopus. Cell 61, 811–23.CrossRefGoogle ScholarPubMed
Draetta, G., Luca, F., Westendorf, J., Ruderman, J. & Beach, D. (1989). cdc2 protein kinase is complexed with cyclin A and B: evidence for proteolytic inactivation of MPF. Cell 56, 829–38.CrossRefGoogle Scholar
Ducommun, B., Brambilla, P., Félix, M.A., Franza, B.R., Karsenti, E. & Draetta, G. (1991). cdc2 phosphorylation is required for its interaction with cyclin. EMBO J. 10, 3311–20.CrossRefGoogle ScholarPubMed
Dunphy, W.G. & Kumagai, A. (1991). The cdc25 protein contains an intrinsic phosphatase activity. Cell 67, 189–96.CrossRefGoogle ScholarPubMed
Dunphy, W.G. & Newport, J.W. (1989). Fission yeast pl3 blocks mitotic activation and tyrosine dephosphorylation of the Xenopus cdc2 protein kinase. Cell 58, 181–91.CrossRefGoogle Scholar
Edgecombe, M., Patel, R. & Whitaker, M. (1991). Cyclinabundance cycle-independent p35cdc2 tyrosine phosphorylation cycle in early sea urchin embryos. EMBO J. 10, 3769–75.CrossRefGoogle ScholarPubMed
Endo, M. (1977). Calcium release from the endoplasmic reticulum. Physiol. Rev. 57, 71–108.CrossRefGoogle Scholar
Enoch, T. & Nurse, P. (1990). Mutation of fission yeast cell cycle control genes abolishes dependence of mitosis on DNA replication. Cell 60, 665–73.CrossRefGoogle ScholarPubMed
Evans, T., Rosenthal, E.T., Youngbloom, J., Distel, D. & Hunt, T. (1983). Cyclin: a protein specified by maternal mRNA in sea urchin eggs that is destroyed at each cleavage division. Cell 33, 389–96.CrossRefGoogle ScholarPubMed
Fernandez, A., Vandromme, M., Basset, M., Cavadore, J.C. & Lamb, N.J.C. (1991). Active intracellular inhibition of the cAMP-dependent protein kinase by microinjection of a modified form of the specific inhibitor peptide PKI in living fibroblasts. Exp. Cell Res. 195, 468–77.CrossRefGoogle ScholarPubMed
Gautier, J., Minshull, J., Lohka, M., Glotzer, M., Hunt, T. & Maller, J. L. (1990). Cyclin is a component of maturation-promoting factor from Xenopus. Cell 60, 487–94.CrossRefGoogle ScholarPubMed
Goris, J., Hermann, P., Hendrix, R., Ozin, R. & Merlevede, W. (1989). Okadaic acid, a specific protein phosphatase inhibitor, induces maturation and MPF formation in Xenopus laevis oocytes. FEBS Lett. 245, 91–4.CrossRefGoogle ScholarPubMed
Gould, K.L. & Nurse, P. (1989). Tyrosine phosphorylation of the fission yeast cdc2+ protein kinase regulates entry into mitosis. Nature 342, 39–45.CrossRefGoogle ScholarPubMed
Gould, K.L., Moreno, S., Owen, D.J., Sazer, S. & Nurse, P. (1991). Phosphorylation at Thrl67 is required for Schizosaccharomyces pombe p34cdc2 function. EMBO J. 10, 3297–309.CrossRefGoogle ScholarPubMed
Harris, P. (1994). Caffeine-induced calcium release in sea urchin eggs and the effect of continuous versus pulsed application on the mitotic apparatus. Dev. Biol. 161, 370–8.CrossRefGoogle ScholarPubMed
Hartwell, L.H. & Weinert, T.A. (1989). Checkpoints: controls that ensure the order of cell cycle events. Science 246, 629–34.CrossRefGoogle ScholarPubMed
Ishida, Y., Furukawa, Y., Decapria, J.A., Saito, M. & Griffin, J.D. (1992). Treatment of myeloid leukemic cells with the phosphatase inhibitor okadaic acid induces cell cycle arrest at either G1/S or G2/M depending on the dose. J. Cell Physiol. 150, 484–92.CrossRefGoogle ScholarPubMed
Jung, T. & Streffer, C. (1992). Effects of caffeine on protein phosphorylation and cell cycle progression in X-irradiated two-cell mouse embryos. Int. J. Radiat. Biol. 62, 161–8.CrossRefGoogle ScholarPubMed
Kanemura, Y., Rossowska, M.J., Narayanan, C.H. & Nakamoto, T. (1992). Effect of caffeine and zinc on DNA and protein synthesis of neonatal rat cardiac muscle cells in culture. Res. Exp. Med. (Berl.) 192, 115–22.CrossRefGoogle Scholar
Krek, W. & Nigg, E.A. (1991). Differential phosphorylation of vertebrate p34cdc2 kinase at the G1/S and G2/M transitions of the cell cycle: identification of the major phosphorylation sites. EMBO J. 10, 305–16.CrossRefGoogle ScholarPubMed
Labbé, J.C., Picard, A., Peaucellier, G., Cavadore, J., Nurse, P. & Dorée, M. (1989). Purification of MPF from starfish: identification as the H1 histone kinase p34cdc2 and a possible mechanism for its periodic activation. Cell 57, 253–63.CrossRefGoogle Scholar
Lau, C.C. & Pardee, A.B. (1982). Mechanism by which caffeine potentiates lethality of nitrogen mustard. Proc. Natl. Acad. Sci. USA 79, 2942–6.CrossRefGoogle ScholarPubMed
Lee, T.H., Solomon, M.J., Mumby, M.C. & Kirschner, M. (1991). INH, a negative regulator of MPF, is a form of protein phosphatase 2A. Cell 64, 415–23.CrossRefGoogle ScholarPubMed
Lundgren, K., Walworth, N., Booher, R., Dembski, M., Kirshner, M. & Beach, D. (1991). mik1 and wee1 cooperate in the inhibitory tyrosine phosphorylation of cdc2. Cell 64, 1111–22.CrossRefGoogle ScholarPubMed
Matsumoto, T. & Beach, D. (1991). Premature initiation of mitosis in yeast lacking RCC1 or an interacting GTPase. Cell 66, 347–60.CrossRefGoogle ScholarPubMed
Meijer, L., Arion, D., Golstein, R., Pines, J., Brizuela, L., Hunt, T. & Beach, D. (1989). Cyclin is a component of the sea urchin egg M-phase specific histone H1 kinase. EMBO J. 8, 2275–82.CrossRefGoogle ScholarPubMed
Meijer, L., Azzi, L. & Wang, J.Y.J. (1991). Cyclin B targets p34cdc2 for tyrosine phosphorylation. EMBO J. 10, 1545–54.CrossRefGoogle ScholarPubMed
Minshull, J., Golstyn, R., Hill, C.S. & Hunt, T. (1990). The A-and B-type cyclins rum on and off at different times in the cell cycle. EMBO J. 9, 2865–75.CrossRefGoogle Scholar
Morgan, D.O. (1995). Principles of CDK regulation. Nature 374, 131–4.CrossRefGoogle ScholarPubMed
Murray, A.W. (1992). Creative blocks: cell-cycle checkpoints and feedback controls. Nature 359, 599–604.CrossRefGoogle ScholarPubMed
Nishimoto, T., Eilen, E. & Basilico, C. (1978). Premature chromosome condensation in a ts DNA− mutant of BHK cells. Cell 15, 475–83.CrossRefGoogle Scholar
Norbury, C., Blow, J. & Nurse, P. (1991). Regulatory phosphorylation of the p34cdc2 protein kinase in vertebrates. EMBO J. 10, 3321–9.CrossRefGoogle ScholarPubMed
Nurse, P. (1990). Universal control mechanism regulating onset of M-phase. Nature 344, 503–8.CrossRefGoogle ScholarPubMed
Osmani, S.A., Engle, D.B., Doonan, J.H. & Morris, N.R. (1988). Spindle formation and chromatin condensation in cells blocked at interphase by mutation of a negative cell cycle control gene. Cell 52, 241–51.CrossRefGoogle ScholarPubMed
Patel, R., Twigg, J., Sheppard, B. & Whitaker, M. (1989). Calcium, cyclin and cell cycle control in sea urchin embryos. In Developmental Biology, UCLA Symposia in Molecular and Cellular Biology, New Series, vol. 125, ed. Davidson, E., Ruderman, J. & Posakony, J., pp. 21–35. New York: Wiley-Liss.Google Scholar
Patel, R. & Whitaker, M. (1991). Okadaic acid suppresses calcium regulation of mitosis onset in sea urchin embryos. Cell Regulation 2, 391–402.CrossRefGoogle ScholarPubMed
Picard, A., Capony, J.P., Brautigan, D.L. & Dorée, M. (1989). Involvement of protein phosphatases 1 and 2A in the control of M-phase-promoting factor activity in starfish. J. Cell Biol. 109, 3347–54.CrossRefGoogle ScholarPubMed
Roberge, M. (1992). Checkpoint controls that couple mitosis to completion of DNA replication. Trends Cell Biol. 2, 277–81.CrossRefGoogle ScholarPubMed
Rowley, R., Hudson, J. & Young, P.G. (1992). The weel protein kinase is required for radiation-induced mitotic delay. Nature 356, 353–5.CrossRefGoogle Scholar
Russell, P. & Nurse, P. (1987). Negative regulation of mitosis by weel +, a gene encoding a protein kinase homolog. Cell 49, 559–67.CrossRefGoogle Scholar
Schlegel, R. & Pardee, A.B. (1987). Caffeine-induced uncoupling of mitosis from the completion of DNA replication in mammalian cells. Science 232, 1264–6.CrossRefGoogle Scholar
Schlegel, R., Belinsky, G.S. & Harris, M.O. (1990). Premature mitosis induced in mammalian cells by the protein kinase inhibitors 2-aminopurine and 6-dimethylaminopurine. Cell Growth Differ. 1, 171–8.Google ScholarPubMed
Sluder, G. & Lewis, K. (1987). Relationship between nuclear DNA synthesis and centrosome reproduction in sea urchin eggs. J. Exp. Biol. 244, 89–100.Google ScholarPubMed
Sluder, G., Thompson, E.A., Rieder, C.L. & Miller, F.J. (1995). Nuclear envelope breakdown is under nuclear not cytoplasmic control in sea urchin zygotes. J. Cell Biol. 129, 1447–58.CrossRefGoogle Scholar
Smythe, C. & Newport, J.W. (1992). Coupling of mitosis to the completion of S phase in Xenopus occurs via modulation of the tyrosine kinase that phosphorylates p34cdc2. Cell 68, 787–97.CrossRefGoogle Scholar
Steinhardt, R.A. & Alderton, J. (1988). Intracellular free calcium rise triggers nuclear envelope breakdown in the sea urchin embryo. Nature 332, 364–6.CrossRefGoogle ScholarPubMed
Steinmann, K. E., Belionsky, G.S., Lee, D. & Schlegel, R. (1991). Chemically induced premature mitosis: differential response in rodent and human cells and the relationship to cyclin B synthesis and p34cdc2/cyclin B complex formation. Proc. Natl. Acad. Sci. USA 88, 6843–7.CrossRefGoogle ScholarPubMed
Twigg, J., Patel, R. & Whitaker, M.J. (1988). Translational control of InsP3-induced chromatin condensation during the early cell cycles of sea urchin embryos. Nature 332, 366–9.CrossRefGoogle ScholarPubMed
Wasserman, W.J. & Masui, Y. (1975). Effects of cycloheximide on a cytoplasmic factor initiating meiotic maturation in Xenopus oocytes. Exp. Cell Res. 91, 381–8.CrossRefGoogle Scholar
Yamashita, K., Yasuda, H., Pines, J., Yasumoto, K., Nishitani, H., Ohtsubo, M., Hunter, T., Sugimura, T. & Nishimoto, T. (1990). Okadaic acid, a potent inhibitor of type 1 and type 2A protein phosphatases, activates cdc2/H1 kinase and transiently induced a premature mitosis-like state in BHK21 cells. EMBO J. 9, 4331–8.CrossRefGoogle Scholar
Yasumasu, I., Fujiwara, A. & Ishida, K. (1973). Periodic changes in the content of adenosine 3',5'-cyclic monophosphate with close relation to the cycle of cleavage in the sea urchin egg. Biochem. Biophys. Res. Commun. 54, 628–32.CrossRefGoogle Scholar