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Polo kinase links the stress pathway to cell cycle control and tip growth in fission yeast

Nature volume 435, pages 507–512 (2005)Cite this article

Abstract

Stress-activated mitogen-activated protein kinase cascades instigate a range of changes to enable eukaryotic cells to cope with particular insults. In Schizosaccharomyces pombe these responses include the transcription of specific gene sets and inhibition of entry into mitosis1,2. The S. pombe stress response pathway (SRP) also promotes commitment to mitosis in unperturbed cell cycles to allow cells to match their rate of division with nutrient availability1,3. The nature of this SRP function in cell cycle control is unknown. Entry into mitosis is controlled by mitosis-promoting factor (MPF; Cdc2/cyclin B) activity. Inhibitory phosphorylation of Cdc2 by Wee1 kinase inactivates MPF until Cdc25 removes this phosphate to promote mitosis4. The balance between Wee1 and Cdc25 activities is influenced by the recruitment of polo kinase (Plo1) to the spindle pole body (SPB)5. The SPB component Cut12 mediates this recruitment5,6. Hyper-activating mutations in either cut12 or plo1 enable Cdc25-defective cells to enter mitosis5,7. The hyperactive cut12.s11 mutation suppresses cdc25.22, as it promotes recruitment of active Plo1 to interphase SPBs6,7. Here we show that the SRP promotes phosphorylation of Plo1 on Ser 402. In unperturbed cell cycles, SRP-mediated phosphorylation of Ser 402 promotes Plo1 recruitment to SPBs and thus commitment to mitosis. Ser 402 phosphorylation also ensures efficient reinitiation of cell tip growth and cell division during recovery from particular stresses. Thus, phosphorylation of Plo1 Ser 402 not only enables SRP signalling to modulate the timing of mitotic commitment in response to nutrient status in unperturbed cycles, but also promotes the return to normal cell cycle control after stress.

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Figure 1: SRP-dependent phosphorylation of Plo1 on Ser 402 influences Plo1 function.
Figure 2: Ser 402 is phosphorylated in a manner dependent on cell cycle position and SRP, and can be mutated to compensate for the sty1.Δ mitotic commitment defect.
Figure 3: Phosphorylation of Plo1 on Ser 402 promotes its association with the SPB and influences its ability to control commitment to mitosis.
Figure 4: SRP dependent phosphorylation of Plo1 Ser 402 promotes tip growth and cell division after stress.

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References

  1. Toone, W. M. & Jones, N. in The Molecular Biology of Schizosaccharomyces pombe (ed. Egel, R.) 57–72 (Springer, Berlin, 2004)

    Book  Google Scholar 

  2. Chen, D. et al. Global transcriptional responses of fission yeast to environmental stress. Mol. Biol. Cell 14, 214–229 (2003)

    Article  CAS  Google Scholar 

  3. Shiozaki, K. & Russell, P. Cell-cycle control linked to extracellular environment by MAP kinase pathway in fission yeast. Nature 378, 739–743 (1995)

    Article  ADS  CAS  Google Scholar 

  4. Nurse, P. Universal control mechanism regulating onset of M-phase. Nature 344, 503–508 (1990)

    Article  ADS  CAS  Google Scholar 

  5. MacIver, F. H., Tanaka, K., Robertson, A. M. & Hagan, I. M. Physical and functional interactions between polo kinase and the spindle pole component Cut12 regulate mitotic commitment in S. pombe. Genes Dev. 17, 1507–1523 (2003)

    Article  CAS  Google Scholar 

  6. Mulvihill, D. P., Petersen, J., Ohkura, H., Glover, D. M. & Hagan, I. M. Plo1 kinase recruitment to the spindle pole body and its role in cell division in Schizosaccharomyces pombe. Mol. Biol. Cell 10, 2771–2785 (1999)

    Article  CAS  Google Scholar 

  7. Hudson, J. D., Feilotter, H. & Young, P. G. stf1: non wee mutations epistatic to cdc25 in the fission yeast Schizosaccharomyces pombe. Genetics 126, 309–315 (1990)

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Soloaga, A. et al. MSK2 and MSK1 mediate the mitogen- and stress-induced phosphorylation of histone H3 and HMG-14. EMBO J. 22, 2788–2797 (2003)

    Article  CAS  Google Scholar 

  9. Nowak, S. J. & Corces, V. G. Phosphorylation of histone H3: a balancing act between chromosome condensation and transcriptional activation. Trends Genet. 20, 214–220 (2004)

    Article  CAS  Google Scholar 

  10. Nurse, P. Genetic control of cell size at cell division in yeast. Nature 256, 547–551 (1975)

    Article  ADS  CAS  Google Scholar 

  11. Mitchison, J. M. & Nurse, P. Growth in cell length in the fission yeast Schizosaccharomyces pombe. J. Cell Sci. 75, 357–376 (1985)

    CAS  PubMed  Google Scholar 

  12. Qian, Y. W., Erikson, E. & Maller, J. L. Mitotic effects of a constitutively active mutant of the Xenopus polo-like kinase Plx1. Mol. Cell. Biol. 19, 8625–8632 (1999)

    Article  CAS  Google Scholar 

  13. Shiozaki, K., Shiozaki, M. & Russell, P. Heat stress activates fission yeast Spc1/StyI MAPK by a MEKK-independent mechanism. Mol. Biol. Cell 9, 1339–1349 (1998)

    Article  CAS  Google Scholar 

  14. Nguyen, A. N. & Shiozaki, K. Heat-shock-induced activation of stress MAP kinase is regulated by threonine- and tyrosine-specific phosphatases. Genes Dev. 13, 1653–1663 (1999)

    Article  CAS  Google Scholar 

  15. May, J. & Mitchison, J. M. Length growth in fission yeast cells measured by two novel techniques. Nature 322, 752–754 (1986)

    Article  ADS  Google Scholar 

  16. Marks, J. & Hyams, J. S. Localization of F-actin through the cell-division cycle of Schizosaccharomyces pombe. Eur. J. Cell Biol. 39, 27–32 (1985)

    Google Scholar 

  17. Nurse, P., Thuriaux, P. & Nasmyth, K. Genetic control of the cell division cycle in the fission yeast Schizosaccharomyces pombe. Mol. Gen. Genet. 146, 167–178 (1976)

    Article  CAS  Google Scholar 

  18. Toczyski, D. P., Galgoczy, D. J. & Hartwell, L. H. CDC5 and CKII control adaptation to the yeast DNA damage checkpoint. Cell 90, 1097–1106 (1997)

    Article  CAS  Google Scholar 

  19. Yoo, H. Y., Kumagai, A., Shevchenko, A. & Dunphy, W. G. Adaptation of a DNA replication checkpoint response depends upon inactivation of claspin by the Polo-like kinase. Cell 117, 575–588 (2004)

    Article  CAS  Google Scholar 

  20. Van Vugt, M. A., Bras, A. & Medema, R. H. Polo-like kinase-1 controls recovery from a G2 DNA damage-induced arrest in mammalian cells. Mol. Cell 15, 799–811 (2004)

    Article  CAS  Google Scholar 

  21. Ogden, J. E. & Fantes, P. A. Isolation of a novel type of mutation in the mitotic control of Schizosaccharomyces pombe whose phenotypic-expression is dependent on the genetic background and nutritional environment. Curr. Genet. 10, 509–514 (1986)

    Article  CAS  Google Scholar 

  22. Moreno, S., Klar, A. & Nurse, P. Molecular genetic analysis of fission yeast Schizosaccharomyces pombe. Methods Enzymol. 194, 795–823 (1991)

    Article  CAS  Google Scholar 

  23. Maundrell, K. Thiamine-repressible expression vectors pREP and pRIP for fission yeast. Gene 123, 127–130 (1993)

    Article  CAS  Google Scholar 

  24. MacIver, F. H., Glover, D. M. & Hagan, I. M. A ‘marker switch’ approach for targeted mutagenesis of genes in Schizosaccharomyces pombe. Yeast 20, 587–594 (2003)

    Article  CAS  Google Scholar 

  25. Caspari, T. et al. Characterization of Schizosaccharomyces pombe Hus1: a PCNA-related protein that associates with Rad1 and Rad9. Mol. Cell. Biol. 20, 1254–1262 (2000)

    Article  CAS  Google Scholar 

  26. Elia, A. E. et al. The molecular basis for phosphodependent substrate targeting and regulation of Plks by the Polo-box domain. Cell 115, 83–95 (2003)

    Article  CAS  Google Scholar 

  27. Elia, A. E., Cantley, L. C. & Yaffe, M. B. Proteomic screen finds pSer/pThr-binding domain localizing Plk1 to mitotic substrates. Science 299, 1228–1231 (2003)

    Article  ADS  CAS  Google Scholar 

  28. Simanis, V. & Nurse, P. The cell-cycle control gene cdc2+ of fission yeast encodes a protein-kinase potentially regulated by phosphorylation. Cell 45, 261–268 (1986)

    Article  CAS  Google Scholar 

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Acknowledgements

We thank A. Grallert for technical assistance in the initial stages of the project; K. Gull, P. Russell, H. Ohkura and N. Jones for reagents; Paul Nurse for support; and N. Jones and P. Nurse for discussions. This work was supported by Cancer Research UK and Rockefeller University.

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Authors and Affiliations

  1. Cancer Research UK Cell Division Group, Paterson Institute for Cancer Research, Wilmslow Road, M20 4BX, Manchester, UK

    Janni Petersen & Iain M. Hagan

  2. The Rockefeller University, Box 5, Room 801, WRB, 1230 York Avenue, New York, New York, 10021, USA

    Janni Petersen

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  1. Janni Petersen
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Correspondence to Iain M. Hagan.

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Supplementary information

Supplementary Figures and Supplementary Table S1

Supplementary Figure S1 shows characterization of the phospho-S402 antibody and phosphorylation of serine 402 under different stress conditions. Supplementary Figure S2 shows the kinetics of S402 phosphorylation after heat shift of cdc25.22 and synchronized wild-type cells along with the kinetics of Spc1/Sty1 activation and the association between Plo1 and Spc1/Sty1 after heat stress. Supplementary Figure S3 shows that centrifugation de-polarizes the F-actin cytoskeleton. Supplementary Figure S4 shows that Plo1 does not dimerise after temperature shift because it is not possible to precipitate untagged Plo1 with epitope tagged Plo1. Supplementary Figure S5 shows a cartoon that summarizes the function of phosphorylation of S402 in cell cycle control and recovery from stress. (PPT 5761 kb)

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Petersen, J., Hagan, I. Polo kinase links the stress pathway to cell cycle control and tip growth in fission yeast. Nature 435, 507–512 (2005). https://doi.org/10.1038/nature03590

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