Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

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

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.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

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.

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)

    CAS  Article  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)

    CAS  Article  Google Scholar 

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

    CAS  Article  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)

    CAS  Article  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)

    CAS  Article  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)

    CAS  Article  Google Scholar 

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

    ADS  CAS  Article  Google Scholar 

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

    CAS  Article  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)

    ADS  CAS  Article  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)

    CAS  Article  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)

    CAS  Article  Google Scholar 

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

    ADS  CAS  Article  Google Scholar 

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

    CAS  Article  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)

    CAS  Article  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)

    CAS  Article  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)

    CAS  Article  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)

    CAS  Article  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)

    CAS  Article  Google Scholar 

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

    CAS  Article  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)

    CAS  Article  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)

    CAS  Article  Google Scholar 

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

    CAS  Article  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)

    CAS  Article  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)

    CAS  Article  Google Scholar 

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

    CAS  Article  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)

    CAS  Article  Google Scholar 

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

    CAS  Article  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)

    ADS  CAS  Article  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)

    CAS  Article  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)

    CAS  Article  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.

Author information

Authors and Affiliations

Authors

Corresponding authors

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

Ethics declarations

Competing interests

Reprints and permissions information is available at www.nature.com/reprints. The authors declare no competing financial interests.

Supplementary information

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)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature05339

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing