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Polo kinase controls cell-cycle-dependent transcription by targeting a coactivator protein

Nature volume 444, pages 494–498 (2006)Cite this article

Abstract

Polo kinases have crucial conserved functions in controlling the eukaryotic cell cycle through orchestrating several events during mitosis1,2. An essential element of cell cycle control is exerted by altering the expression of key regulators3. Here we show an important function for the polo kinase Cdc5p in controlling cell-cycle-dependent gene expression that is crucial for the execution of mitosis in the model eukaryote Saccharomyces cerevisiae. In particular, we find that Cdc5p is temporally recruited to promoters of the cell-cycle-regulated CLB2 gene cluster, where it targets the Mcm1p–Fkh2p–Ndd1p transcription factor complex, through direct phosphorylation of the coactivator protein Ndd1p. This phosphorylation event is required for the normal temporal expression of cell-cycle-regulated genes such as CLB2 and SWI5 in G2/M phases. Furthermore, severe defects in cell division occur in the absence of Cdc5p-mediated phosphorylation of Ndd1p. Thus, polo kinase is required for the production of key mitotic regulators, in addition to previously defined roles in controlling other mitotic events.

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Figure 1: Cdc5p is recruited to CLB2 gene cluster promoters and phosphorylates Ndd1p.
Figure 2: Ndd1p is phosphorylated at Ser 85 by Cdc5p.
Figure 3: Ser 85 of Ndd1p is required for several cell-cycle-dependent processes.
Figure 4: Ser 85 of Ndd1p is required for normal promoter recruitment and CLB2 gene cluster expression.

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References

  1. Barr, F. A., Silljé, H. H. W. & Nigg, E. A. Polo-like kinases and the orchestration of cell division. Nature Rev. Mol. Cell Biol. 5, 429–441 (2004)

    Article  CAS  Google Scholar 

  2. Lee, K. S., Park, J. E., Asano, S. & Park, C. J. Yeast polo-like kinases: functionally conserved multitask mitotic regulators. Oncogene 24, 217–229 (2005)

    Article  CAS  Google Scholar 

  3. Wittenberg, C. & Reed, S. I. Cell cycle-dependent transcription in yeast: promoters, transcription factors, and transcriptomes. Oncogene 24, 2746–2755 (2005)

    Article  CAS  Google Scholar 

  4. Alexandru, G., Uhlmann, F., Mechtler, K., Poupart, M. & Nasmyth, K. Phosphorylation of the cohesin subunit Scc1 by Polo/Cdc5 kinase regulates sister chromatid separation in yeast. Cell 105, 459–472 (2001)

    Article  CAS  Google Scholar 

  5. Hu, F. et al. Regulation of the Bub2/Bfa1 GAP complex by Cdc5 and cell cycle checkpoints. Cell 107, 655–665 (2001)

    Article  CAS  Google Scholar 

  6. Geymonat, M., Spanos, A., Walker, P. A., Johnston, L. H. & Sedgwick, S. G. In vitro regulation of budding yeast Bfa1/Bub2 GAP activity by Cdc5. J. Biol. Chem. 278, 14591–14594 (2003)

    Article  CAS  Google Scholar 

  7. Sakchaisri, K. et al. Coupling morphogenesis to mitotic entry. Proc. Natl Acad. Sci. USA 101, 4124–4129 (2004)

    Article  ADS  CAS  Google Scholar 

  8. Futcher, B. Transcriptional regulatory networks and the yeast cell cycle. Curr. Opin. Cell Biol. 14, 676–683 (2002)

    Article  CAS  Google Scholar 

  9. Koranda, M., Schleiffer, A., Endler, L. & Ammerer, G. Forkhead-like transcription factors recruit Ndd1 to the chromatin of G2/M-specific promoters. Nature 406, 94–98 (2000)

    Article  ADS  CAS  Google Scholar 

  10. Kumar, R. et al. Forkhead transcription factors, Fkh1p and Fkh2p, collaborate with Mcm1p to control transcription required for M-phase. Curr. Biol. 10, 896–906 (2000)

    Article  CAS  Google Scholar 

  11. Pic, A. et al. The forkhead protein Fkh2 is a component of the yeast cell cycle transcription factor SFF. EMBO J. 19, 3750–3761 (2000)

    Article  CAS  Google Scholar 

  12. Zhu, G. et al. Two yeast forkhead genes regulate the cell cycle and pseudohyphal growth. Nature 406, 90–94 (2000)

    Article  ADS  CAS  Google Scholar 

  13. Breeden, L. L. Cyclin transcription: Timing is everything. Curr. Biol. 10, R586–R588 (2000)

    Article  CAS  Google Scholar 

  14. Pic-Taylor, A., Darieva, Z., Morgan, B. A. & Sharrocks, A. D. Regulation of cell cycle-specific gene expression through cyclin-dependent kinase-mediated phosphorylation of the forkhead transcription factor Fkh2p. Mol. Cell. Biol. 24, 10036–10046 (2004)

    Article  CAS  Google Scholar 

  15. Darieva, Z. et al. Cell cycle regulated transcription through the FHA domain of Fkh2p and the coactivator Ndd1p. Curr. Biol. 13, 1740–1745 (2003)

    Article  CAS  Google Scholar 

  16. Reynolds, D. et al. Recruitment of Thr 319-phosphorylated Ndd1p to the FHA domain of Fkh2p requires Clb kinase activity: a mechanism for CLB cluster gene activation. Genes Dev. 17, 1789–1802 (2003)

    Article  CAS  Google Scholar 

  17. Cheng, L., Hunke, L. & Hardy, C. F. Cell cycle regulation of the Saccharomyces cerevisiae polo-like kinase cdc5p. Mol. Cell. Biol. 18, 7360–7370 (1998)

    Article  CAS  Google Scholar 

  18. Nakajima, H., Toyoshima-Morimoto, F., Taniguchi, E. & Nishida, E. Identification of a consensus motif for Plk (Polo-like kinase) phosphorylation reveals Myt1 as a Plk1 substrate. J. Biol. Chem. 278, 25277–25280 (2003)

    Article  CAS  Google Scholar 

  19. Song, S. & Lee, K. S. A novel function of Saccharomyces cerevisiae CDC5 in cytokinesis. J. Cell Biol. 152, 451–469 (2001)

    Article  CAS  Google Scholar 

  20. Althoefer, H., Schleiffer, A., Wassmann, K., Nordheim, A. & Ammerer, G. Mcm1 is required to coordinate G2-specific transcription in Saccharomyces cerevisiae.. Mol. Cell. Biol. 15, 5917–5928 (1995)

    Article  CAS  Google Scholar 

  21. Spellman, P. T. et al. Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization. Mol. Biol. Cell 9, 3273–3297 (1998)

    Article  CAS  Google Scholar 

  22. Simon, I. Serial regulation of transcriptional regulators in the yeast cell cycle. Cell 106, 697–708 (2001)

    Article  CAS  Google Scholar 

  23. Asano, S. et al. Concerted mechanism of Swe1/Wee1 regulation by multiple kinases in budding yeast. EMBO J. 24, 2194–2204 (2005)

    Article  CAS  Google Scholar 

  24. Zilahi, E., Salimova, E., Simanis, V. & Sipiczki, M. The S. pombe sep1 gene encodes a nuclear protein that is required for periodic expression of the cdc15 gene. FEBS Lett. 481, 105–108 (2000)

    Article  CAS  Google Scholar 

  25. Buck, V. et al. Fkh2p and Sep1p regulate mitotic gene transcription in fission yeast. J. Cell Sci. 117, 5623–5632 (2004)

    Article  CAS  Google Scholar 

  26. Bulmer, R. et al. The forkhead transcription factor Fkh2 regulates the cell division cycle of Schizosaccharomyces pombe. Eukaryot. Cell 3, 944–954 (2004)

    Article  CAS  Google Scholar 

  27. Rustici, G. et al. Periodic gene expression program of the fission yeast cell cycle. Nature Genet. 36, 809–817 (2004)

    Article  CAS  Google Scholar 

  28. Alvarez, B., Martinez, A. C., Burgering, B. M. & Carrera, A. C. Forkhead transcription factors contribute to execution of the mitotic programme in mammals. Nature 413, 744–747 (2001)

    Article  ADS  CAS  Google Scholar 

  29. Laoukili, J. et al. FoxM1 is required for execution of the mitotic programme and chromosome stability. Nature Cell Biol. 7, 126–136 (2005)

    Article  CAS  Google Scholar 

  30. Anderson, M. et al. Plo1+ regulates gene transcription at the M–G1 interval during the fission yeast mitotic cell cycle. EMBO J. 21, 5745–5755 (2002)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank A. Clancy for technical assistance; I. Hagan, P. March, M. Jackson and G. Pereira for advice; A. Whitmarsh, S.-H. Yang and members of our laboratories for comments on the manuscript and helpful discussions; and M. Walberg, U. Surana, G. Pereira and D. Lydall for reagents. This work was supported by Cancer Research UK, the BBSRC, the MRC and the Wellcome Trust.

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Author notes

  1. Aline Pic-Taylor

    Present address: EMBRAPA Recursos Genéticos e Biotecnologia, Parque Estação Biológica, CP 02372, Final W5 Norte, Brasília, DF CEP 70770-900, Brazil

Authors and Affiliations

  1. Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK

    Zoulfia Darieva & Andrew D. Sharrocks

  2. Institute for Cell and Molecular Biosciences, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK

    Richard Bulmer, Aline Pic-Taylor, Kathryn S. Doris & Brian A. Morgan

  3. Division of Yeast Genetics, National Institute for Medical Research, Mill Hill, London, NW7 1AA, UK

    Marco Geymonat & Steven G. Sedgwick

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Correspondence to Brian A. Morgan or Andrew D. Sharrocks.

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Supplementary Notes

This file contains Supplementary Methods and Supplementary Figure Legends. (DOC 75 kb)

Supplementary Figures

This file contains Supplementary Figures 1–11. (PDF 291 kb)

Supplementary Data

This is a list of the key genes and proteins used in this study. (DOC 23 kb)

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Darieva, Z., Bulmer, R., Pic-Taylor, A. et al. Polo kinase controls cell-cycle-dependent transcription by targeting a coactivator protein . Nature 444, 494–498 (2006). https://doi.org/10.1038/nature05339

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