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Polo-like kinases: conservation and divergence in their functions and regulation

Nature Reviews Molecular Cell Biology volume 10, pages 265–275 (2009)Cite this article

A Corrigendum to this article was published on 02 April 2009

Key Points

  • Polo-like kinases (Plks) are conserved from yeasts to humans but are absent from plants. The Plk family is characterized by the presence of an amino-terminal kinase domain and a carboxy-terminal Polo-box domain (PBD) that mediates protein interactions with target proteins.

  • Plks fulfil many roles in cell division, including the regulation of entry into M phase, spindle pole biogenesis and function, mitotic chromosome dynamics, mitotic exit and cytokinesis. Many of these functions have been characterized in detailed molecular terms, although some pathways remain to be elucidated.

  • The regulation of Plks is achieved through a combination of transcriptional control, reversible phosphorylation that changes the kinase activity, ubiquitin-dependent proteolysis and protein interactions. The precise mode of regulation differs between Plks and adapts according to the biological context.

  • Roles for Plks outside of basic cell division are now fast emerging. Plks function in coordinating cell division in the developmental programme of various organisms, including flies and worms, in the establishment of asymmetry in several situations, and even in differentiated cells, such as human neurons.

Abstract

Polo-like kinases (Plks) are potent regulators of M phase that are conserved from yeasts to humans. Their roles in mitotic entry, spindle pole functions and cytokinesis are broadly conserved despite physical and molecular differences in these processes in disparate organisms. Plks are characterized by their Polo-box domain, which mediates protein interactions. They are additionally controlled by phosphorylation, proteolysis and transcription, depending on the biological context. Plks are now recognized to link cell division to developmental processes and to function in differentiated cells. A comparison of Plk function and regulation between organisms offers insight into the rich variations of cell division.

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Figure 1: Summary of selected Polo-like kinase functions in the cell cycle.
Figure 2: Localization of Polo-like kinases during the cell cycle.
Figure 3: Four levels of regulation shared by many Polo-like kinases.
Figure 4: Developmental regulation of Polo-like kinases at entry into M phase.

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References

  1. Sunkel, C. E. & Glover, D. M. polo, a mitotic mutant of Drosophila displaying abnormal spindle poles. J. Cell Sci. 89, 25–38 (1988).

    Article  PubMed  Google Scholar 

  2. Llamazares, S. et al. polo encodes a protein kinase homolog required for mitosis in Drosophila. Genes Dev. 5, 2153–2165 (1991). References 1 and 2 report the initial isolation and phenotypic examination of polo mutants in D. melanogaster , the realization that this gene encodes a kinase, and its implication in mitosis.

    Article  CAS  PubMed  Google Scholar 

  3. Bettencourt-Dias, M. et al. SAK/PLK4 is required for centriole duplication and flagella development. Curr. Biol. 15, 2199–2207 (2005).

    Article  CAS  PubMed  Google Scholar 

  4. Habedanck, R., Stierhof, Y. D., Wilkinson, C. J. & Nigg, E. A. The Polo kinase Plk4 functions in centriole duplication. Nature Cell Biol. 7, 1140–1146 (2005). References 3 and 4 show that PLK4 is completely and specifically required for centriole duplication in D. melanogaster and human cells.

    Article  CAS  PubMed  Google Scholar 

  5. Lowery, D. M., Lim, D. & Yaffe, M. B. Structure and function of Polo-like kinases. Oncogene 24, 248–259 (2005).

    Article  CAS  PubMed  Google Scholar 

  6. 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). Identifies the PBD of human PLK1 as a functional unit that is capable of binding phosphorylated peptides and proteins in vitro and in vivo.

    Article  CAS  PubMed  Google Scholar 

  7. 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  PubMed  Google Scholar 

  8. Cheng, K. Y., Lowe, E. D., Sinclair, J., Nigg, E. A. & Johnson, L. N. The crystal structure of the human polo-like kinase-1 polo box domain and its phospho-peptide complex. EMBO J. 22, 5757–5768 (2003). References 7 and 8 solve crystal structures for the PBD of human PLK1 in complex with a phosphopeptide substrate.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Leung, G. C. et al. The Sak polo-box comprises a structural domain sufficient for mitotic subcellular localization. Nature Struct. Biol. 9, 719–724 (2002).

    Article  CAS  PubMed  Google Scholar 

  10. Petronczki, M., Lenart, P. & Peters, J. M. Polo on the rise-from mitotic entry to cytokinesis with Plk1. Dev. Cell 14, 646–659 (2008).

    Article  CAS  PubMed  Google Scholar 

  11. Strebhardt, K. & Ullrich, A. Targeting polo-like kinase 1 for cancer therapy. Nature Rev. Cancer 6, 321–330 (2006).

    Article  CAS  Google Scholar 

  12. Barr, F. A., Sillje, H. H. & Nigg, E. A. Polo-like kinases and the orchestration of cell division. Nature Rev. Mol. Cell Biol. 5, 429–440 (2004).

    Article  CAS  Google Scholar 

  13. van Vugt, M. A. & Medema, R. H. Getting in and out of mitosis with Polo-like kinase-1. Oncogene 24, 2844–2859 (2005).

    Article  CAS  PubMed  Google Scholar 

  14. van de Weerdt, B. C. & Medema, R. H. Polo-like kinases: a team in control of the division. Cell Cycle 5, 853–864 (2006).

    Article  CAS  PubMed  Google Scholar 

  15. Hagan, I. M. The spindle pole body plays a key role in controlling mitotic commitment in the fission yeast Schizosaccharomyces pombe. Biochem. Soc. Trans. 36, 1097–1101 (2008).

    Article  CAS  PubMed  Google Scholar 

  16. 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  PubMed  Google Scholar 

  17. Kumagai, A. & Dunphy, W. G. Purification and molecular cloning of Plx1, a Cdc25-regulatory kinase from Xenopus egg extracts. Science 273, 1377–1380 (1996). Reports the first isolation of X. laevis Plx1 by virtue of its interaction with Cdc25C. It also constitutes the first molecular implication of a Plk in regulating entry into M phase.

    Article  CAS  PubMed  Google Scholar 

  18. Watanabe, N. et al. M-phase kinases induce phospho-dependent ubiquitination of somatic Wee1 by SCFβ-TrCP. Proc. Natl Acad. Sci. USA 101, 4419–4424 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Inoue, D. & Sagata, N. The Polo-like kinase Plx1 interacts with and inhibits Myt1 after fertilization of Xenopus eggs. EMBO J. 24, 1057–1067 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Petersen, J. & Hagan, I. M. Polo kinase links the stress pathway to cell cycle control and tip growth in fission yeast. Nature 435, 507–512 (2005).

    Article  CAS  PubMed  Google Scholar 

  21. Petersen, J. & Nurse, P. TOR signalling regulates mitotic commitment through the stress MAP kinase pathway and the Polo and Cdc2 kinases. Nature Cell Biol. 9, 1263–1272 (2007).

    Article  CAS  PubMed  Google Scholar 

  22. 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  PubMed  Google Scholar 

  23. 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  PubMed  Google Scholar 

  24. Smits, V. A. et al. Polo-like kinase-1 is a target of the DNA damage checkpoint. Nature Cell Biol. 2, 672–676 (2000).

    Article  CAS  PubMed  Google Scholar 

  25. Bassermann, F. et al. The Cdc14B–Cdh1–Plk1 axis controls the G2 DNA-damage-response checkpoint. Cell 134, 256–267 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. van Vugt, M. A., Brás, 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  PubMed  Google Scholar 

  27. Macurek, L. et al. Polo-like kinase-1 is activated by aurora A to promote checkpoint recovery. Nature 455, 119–123 (2008).

    Article  CAS  PubMed  Google Scholar 

  28. Seki, A., Coppinger, J. A., Jang, C. Y., Yates, J. R. & Fang, G. Bora and the kinase Aurora A cooperatively activate the kinase Plk1 and control mitotic entry. Science 320, 1655–1658 (2008). References 27 and 28 report that Aurora A is responsible for the activating phosphorylation of human PLK1 in the T-loop at mitotic entry during recovery from the DNA damage checkpoint, and in an unperturbed cell cycle, respectively.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Lane, H. A. & Nigg, E. A. Antibody microinjection reveals an essential role for human polo-like kinase 1 (Plk1) in the functional maturation of mitotic centrosomes. J. Cell Biol. 135, 1701–1713 (1996). An elegant, pre-RNA interference set of experiments using PLK1 antibody microinjections, showing that PLK1 is required for centrosome maturation. This agrees with previous observations made in D. melanogaster polo mutants.

    Article  CAS  PubMed  Google Scholar 

  30. Ohkura, H., Hagan, I. M. & Glover, D. M. The conserved Schizosaccharomyces pombe kinase plo1, required to form a bipolar spindle, the actin ring, and septum, can drive septum formation in G1 and G2 cells. Genes Dev. 9, 1059–1073 (1995). The first examination of plo1 mutant phenotypes in fission yeast, including defects both in bipolar spindle formation and in the completion of mitotic division, thereby reconciling previous, seemingly contradictory observations made in the budding yeast cdc5 compared with fly polo mutants.

    Article  CAS  PubMed  Google Scholar 

  31. Snead, J. L. et al. A coupled chemical-genetic and bioinformatic approach to Polo-like kinase pathway exploration. Chem. Biol. 14, 1261–1272 (2007).

    Article  CAS  PubMed  Google Scholar 

  32. Budde, P. P., Kumagai, A., Dunphy, W. G. & Heald, R. Regulation of Op18 during spindle assembly in Xenopus egg extracts. J. Cell Biol. 153, 149–158 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Yarm, F. R. Plk phosphorylation regulates the microtubule-stabilizing protein TCTP. Mol. Cell. Biol. 22, 6209–6221 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. do Carmo Avides, M., Tavares, A. & Glover, D. M. Polo kinase and Asp are needed to promote the mitotic organizing activity of centrosomes. Nature Cell Biol. 3, 421–424 (2001).

    Article  CAS  PubMed  Google Scholar 

  35. Donaldson, M. M., Tavares, A. A., Ohkura, H., Deak, P. & Glover, D. M. Metaphase arrest with centromere separation in polo mutants of Drosophila. J. Cell Biol. 153, 663–676 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Maekawa, H., Priest, C., Lechner, J., Pereira, G. & Schiebel, E. The yeast centrosome translates the positional information of the anaphase spindle into a cell cycle signal. J. Cell Biol. 179, 423–436 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Casenghi, M. et al. Polo-like kinase 1 regulates Nlp, a centrosome protein involved in microtubule nucleation. Dev. Cell 5, 113–125 (2003).

    Article  CAS  PubMed  Google Scholar 

  38. Casenghi, M., Barr, F. A. & Nigg, E. A. Phosphorylation of Nlp by Plk1 negatively regulates its dynein–dynactin-dependent targeting to the centrosome. J. Cell Sci. 118, 5101–5108 (2005).

    Article  CAS  PubMed  Google Scholar 

  39. Oshimori, N., Ohsugi, M. & Yamamoto, T. The Plk1 target Kizuna stabilizes mitotic centrosomes to ensure spindle bipolarity. Nature Cell Biol. 8, 1095–1101 (2006).

    Article  CAS  PubMed  Google Scholar 

  40. De Luca, M., Lavia, P. & Guarguaglini, G. A functional interplay between Aurora-A, Plk1 and TPX2 at spindle poles: Plk1 controls centrosomal localization of Aurora-A and TPX2 spindle association. Cell Cycle 5, 296–303 (2006).

    Article  CAS  PubMed  Google Scholar 

  41. Soung, N. K. et al. Requirement of hCenexin for proper mitotic functions of polo-like kinase 1 at the centrosomes. Mol. Cell. Biol. 26, 8316–8335 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Sutterlin, C. et al. Polo-like kinase is required for the fragmentation of pericentriolar Golgi stacks during mitosis. Proc. Natl Acad. Sci. USA 98, 9128–9132 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Bettencourt-Dias, M. & Glover, D. M. Centrosome biogenesis and function: centrosomics brings new understanding. Nature Rev. Mol. Cell Biol. 8, 451–463 (2007).

    Article  CAS  Google Scholar 

  44. Rodrigues-Martins, A., Riparbelli, M., Callaini, G., Glover, D. M. & Bettencourt-Dias, M. Revisiting the role of the mother centriole in centriole biogenesis. Science 316, 1046–1050 (2007).

    Article  CAS  PubMed  Google Scholar 

  45. Warnke, S. et al. Polo-like kinase-2 is required for centriole duplication in mammalian cells. Curr. Biol. 14, 1200–1207 (2004).

    Article  CAS  PubMed  Google Scholar 

  46. Wang, X. et al. sSgo1, a major splice variant of Sgo1, functions in centriole cohesion where it is regulated by Plk1. Dev. Cell 14, 331–341 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Losada, A. Cohesin regulation: fashionable ways to wear a ring. Chromosoma 116, 321–329 (2007).

    Article  CAS  PubMed  Google Scholar 

  48. Alexandru, G., Uhlmann, F., Mechtler, K., Poupart, M. A. & Nasmyth, K. Phosphorylation of the cohesin subunit Scc1 by Polo/Cdc5 kinase regulates sister chromatid separation in yeast. Cell 105, 459–472 (2001). First demonstration of a Plk targeting cohesins to promote sister chromatid separation.

    Article  CAS  PubMed  Google Scholar 

  49. Hornig, N. C. & Uhlmann, F. Preferential cleavage of chromatin-bound cohesin after targeted phosphorylation by Polo-like kinase. EMBO J. 23, 3144–3153 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Sumara, I. et al. The dissociation of cohesin from chromosomes in prophase is regulated by Polo-like kinase. Mol. Cell 9, 515–525 (2002).

    Article  CAS  PubMed  Google Scholar 

  51. Hauf, S. et al. Dissociation of cohesin from chromosome arms and loss of arm cohesion during early mitosis depends on phosphorylation of SA2. PLoS Biol. 3, e69 (2005).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Lee, B. H. & Amon, A. Role of Polo-like kinase CDC5 in programming meiosis I chromosome segregation. Science 300, 482–486 (2003).

    Article  CAS  PubMed  Google Scholar 

  53. Clyne, R. K. et al. Polo-like kinase Cdc5 promotes chiasmata formation and cosegregation of sister centromeres at meiosis I. Nature Cell Biol. 5, 480–485 (2003).

    Article  CAS  PubMed  Google Scholar 

  54. Clarke, A. S., Tang, T. T., Ooi, D. L. & Orr-Weaver, T. L. POLO kinase regulates the Drosophila centromere cohesion protein MEI-S332. Dev. Cell 8, 53–64 (2005).

    Article  CAS  PubMed  Google Scholar 

  55. Riedel, C. G. et al. Protein phosphatase 2A protects centromeric sister chromatid cohesion during meiosis I. Nature 441, 53–61 (2006).

    Article  CAS  PubMed  Google Scholar 

  56. Kitajima, T. S. et al. Shugoshin collaborates with protein phosphatase 2A to protect cohesin. Nature 441, 46–52 (2006).

    Article  CAS  PubMed  Google Scholar 

  57. Tang, Z. et al. PP2A is required for centromeric localization of Sgo1 and proper chromosome segregation. Dev. Cell 10, 575–585 (2006).

    Article  CAS  PubMed  Google Scholar 

  58. Chen, F. et al. Multiple protein phosphatases are required for mitosis in Drosophila. Curr. Biol. 17, 293–303 (2007).

    Article  PubMed  CAS  Google Scholar 

  59. Kang, Y. H. et al. Self-regulated Plk1 recruitment to kinetochores by the Plk1–PBIP1 interaction is critical for proper chromosome segregation. Mol. Cell 24, 409–422 (2006).

    Article  CAS  PubMed  Google Scholar 

  60. Goto, H. et al. Complex formation of Plk1 and INCENP required for metaphase–anaphase transition. Nature Cell Biol. 8, 180–187 (2006).

    Article  CAS  PubMed  Google Scholar 

  61. Elowe, S., Hummer, S., Uldschmid, A., Li, X. & Nigg, E. A. Tension-sensitive Plk1 phosphorylation on BubR1 regulates the stability of kinetochore microtubule interactions. Genes Dev. 21, 2205–2219 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Qi, W., Tang, Z. & Yu, H. Phosphorylation- and polo-box-dependent binding of Plk1 to Bub1 is required for the kinetochore localization of Plk1. Mol. Biol. Cell 17, 3705–3716 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Ahonen, L. J. et al. Polo-like kinase 1 creates the tension-sensing 3F3/2 phosphoepitope and modulates the association of spindle-checkpoint proteins at kinetochores. Curr. Biol. 15, 1078–1089 (2005).

    Article  CAS  PubMed  Google Scholar 

  64. Wong, O. K. & Fang, G. Plx1 is the 3F3/2 kinase responsible for targeting spindle checkpoint proteins to kinetochores. J. Cell Biol. 170, 709–719 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Wong, O. K. & Fang, G. Cdk1 phosphorylation of BubR1 controls spindle checkpoint arrest and Plk1-mediated formation of the 3F3/2 epitope. J. Cell Biol. 179, 611–617 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Rosasco-Nitcher, S. E., Lan, W., Khorasanizadeh, S. & Stukenberg, P. T. Centromeric Aurora-B activation requires TD-60, microtubules, and substrate priming phosphorylation. Science 319, 469–472 (2008).

    Article  CAS  PubMed  Google Scholar 

  67. Lenart, P. et al. The small-molecule inhibitor BI 2536 reveals novel insights into mitotic roles of polo-like kinase 1. Curr. Biol. 17, 304–315 (2007).

    Article  CAS  PubMed  Google Scholar 

  68. Nishino, M. et al. NudC is required for Plk1 targeting to the kinetochore and chromosome congression. Curr. Biol. 16, 1414–1421 (2006).

    Article  CAS  PubMed  Google Scholar 

  69. Eckerdt, F. & Strebhardt, K. Polo-like kinase 1: target and regulator of anaphase-promoting complex/cyclosome-dependent proteolysis. Cancer Res. 66, 6895–6898 (2006).

    Article  CAS  PubMed  Google Scholar 

  70. Moshe, Y., Boulaire, J., Pagano, M. & Hershko, A. Role of Polo-like kinase in the degradation of early mitotic inhibitor 1, a regulator of the anaphase promoting complex/cyclosome. Proc. Natl Acad. Sci. USA 101, 7937–7942 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Hansen, D. V., Loktev, A. V., Ban, K. H. & Jackson, P. K. Plk1 regulates activation of the anaphase promoting complex by phosphorylating and triggering SCFβTrCP-dependent destruction of the APC inhibitor Emi1. Mol. Biol. Cell 15, 5623–5634 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Liu, J. & Maller, J. L. Calcium elevation at fertilization coordinates phosphorylation of XErp1/Emi2 by Plx1 and CaMK II to release metaphase arrest by cytostatic factor. Curr. Biol. 15, 1458–1468 (2005).

    Article  CAS  PubMed  Google Scholar 

  73. Rauh, N. R., Schmidt, A., Bormann, J., Nigg, E. A. & Mayer, T. U. Calcium triggers exit from meiosis II by targeting the APC/C inhibitor XErp1 for degradation. Nature 437, 1048–1052 (2005).

    Article  CAS  PubMed  Google Scholar 

  74. Hansen, D. V., Tung, J. J. & Jackson, P. K. CaMKII and polo-like kinase 1 sequentially phosphorylate the cytostatic factor Emi2/XErp1 to trigger its destruction and meiotic exit. Proc. Natl Acad. Sci. USA 103, 608–613 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Bardin, A. J. & Amon, A. MEN and SIN: what's the difference? Nature Rev. Mol. Cell Biol. 2, 815–826 (2001).

    Article  CAS  Google Scholar 

  76. Simanis, V. Events at the end of mitosis in the budding and fission yeasts. J. Cell Sci. 116, 4263–4275 (2003).

    Article  CAS  PubMed  Google Scholar 

  77. Bähler, J. et al. Role of Polo kinase and Mid1p in determining the site of cell division in fission yeast. J. Cell Biol. 143, 1603–1616 (1998).

    Article  PubMed  PubMed Central  Google Scholar 

  78. Carmena, M. et al. Drosophila polo kinase is required for cytokinesis. J. Cell Biol. 143, 659–671 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Neef, R. et al. Choice of Plk1 docking partners during mitosis and cytokinesis is controlled by the activation state of Cdk1. Nature Cell Biol. 9, 436–444 (2007).

    Article  CAS  PubMed  Google Scholar 

  80. D'Avino, P. P. et al. Recruitment of Polo kinase to the spindle midzone during cytokinesis requires the Feo/Klp3A complex. PLoS ONE 2, e572 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. Neef, R. et al. Phosphorylation of mitotic kinesin-like protein 2 by polo-like kinase 1 is required for cytokinesis. J. Cell Biol. 162, 863–75 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Burkard, M. E. et al. Chemical genetics reveals the requirement for Polo-like kinase 1 activity in positioning RhoA and triggering cytokinesis in human cells. Proc. Natl Acad. Sci. USA 104, 4383–4388 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Brennan, I. M., Peters, U., Kapoor, T. M. & Straight, A. F. Polo-like kinase controls vertebrate spindle elongation and cytokinesis. PLoS ONE 2, e409 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Petronczki, M., Glotzer, M., Kraut, N. & Peters, J. M. Polo-like kinase 1 triggers the initiation of cytokinesis in human cells by promoting recruitment of the RhoGEF Ect2 to the central spindle. Dev. Cell 12, 713–725 (2007).

    Article  CAS  PubMed  Google Scholar 

  85. Santamaria, A. et al. Use of the novel Plk1 inhibitor ZK-thiazolidinone to elucidate functions of Plk1 in early and late stages of mitosis. Mol. Biol. Cell 18, 4024–4036 (2007). References 82–85 closely examine the requirements for PLK1 in cytokinesis using chemical inhibition.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Yoshida, S. et al. Polo-like kinase Cdc5 controls the local activation of Rho1 to promote cytokinesis. Science 313, 108–111 (2006).

    Article  CAS  PubMed  Google Scholar 

  87. Uchiumi, T., Longo, D. L. & Ferris, D. K. Cell cycle regulation of the human polo-like kinase (PLK) promoter. J. Biol. Chem. 272, 9166–9174 (1997).

    Article  CAS  PubMed  Google Scholar 

  88. 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  CAS  PubMed  Google Scholar 

  89. 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  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  92. Darieva, Z. et al. Polo kinase controls cell-cycle-dependent transcription by targeting a coactivator protein. Nature 444, 494–498 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Papadopoulou, K. et al. Regulation of gene expression during M–G1-phase in fission yeast through Plo1p and forkhead transcription factors. J. Cell Sci. 121, 38–47 (2008).

    Article  CAS  PubMed  Google Scholar 

  94. Fu, Z. et al. Plk1-dependent phosphorylation of FoxM1 regulates a transcriptional programme required for mitotic progression. Nature Cell Biol. 10, 1076–1082 (2008).

    Article  CAS  PubMed  Google Scholar 

  95. Martin, B. T. & Strebhardt, K. Polo-like kinase 1: target and regulator of transcriptional control. Cell Cycle 5, 2881–2885 (2006).

    Article  CAS  PubMed  Google Scholar 

  96. Ren, B. et al. E2F integrates cell cycle progression with DNA repair, replication, and G2/M checkpoints. Genes Dev. 16, 245–256 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Gunawardena, R. W. et al. Hierarchical requirement of SWI/SNF in retinoblastoma tumor suppressor-mediated repression of Plk1. J. Biol. Chem. 279, 29278–29285 (2004).

    Article  CAS  PubMed  Google Scholar 

  98. Wen, H., Andrejka, L., Ashton, J., Karess, R. & Lipsick, J. S. Epigenetic regulation of gene expression by Drosophila Myb and E2F2–RBF via the Myb–MuvB/dREAM complex. Genes Dev. 22, 601–614 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Jang, Y. J., Ma, S., Terada, Y. & Erikson, R. L. Phosphorylation of threonine 210 and the role of serine 137 in the regulation of mammalian polo-like kinase. J. Biol. Chem. 277, 44115–44120 (2002).

    Article  CAS  PubMed  Google Scholar 

  100. 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). Identification of T-loop activation as a potent mechanism of activation of X. laevis Plx1, and of regulating progression through M phase.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Lindon, C. & Pines, J. Ordered proteolysis in anaphase inactivates Plk1 to contribute to proper mitotic exit in human cells. J. Cell Biol. 164, 233–241 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Hutterer, A. et al. Mitotic activation of the kinase Aurora-A requires its binding partner Bora. Dev. Cell 11, 147–157 (2006).

    Article  CAS  PubMed  Google Scholar 

  103. Chan, E. H., Santamaria, A., Sillje, H. H. & Nigg, E. A. Plk1 regulates mitotic Aurora A function through βTrCP-dependent degradation of hBora. Chromosoma 117, 457–469 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Seki, A. et al. Plk1- and β-TrCP-dependent degradation of Bora controls mitotic progression. J. Cell Biol. 181, 65–78 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Yamashiro, S. et al. Myosin phosphatase-targeting subunit 1 regulates mitosis by antagonizing polo-like kinase 1. Dev. Cell 14, 787–797 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. van de Weerdt, B. C. et al. Uncoupling anaphase-promoting complex/cyclosome activity from spindle assembly checkpoint control by deregulating polo-like kinase 1. Mol. Cell. Biol. 25, 2031–2044 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Maroto, B., Ye, M. B., von Lohneysen, K., Schnelzer, A. & Knaus, U. G. P21-activated kinase is required for mitotic progression and regulates Plk1. Oncogene 27, 4900–4908 (2008).

    Article  CAS  PubMed  Google Scholar 

  108. Archambault, V., Zhao, X., White-Cooper, H., Carpenter, A. T. & Glover, D. M. Mutations in Drosophila Greatwall/Scant reveal its roles in mitosis and meiosis and interdependence with Polo kinase. PLoS Genet. 3, e200 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  109. Yu, J., Zhao, Y., Li, Z., Galas, S. & Goldberg, M. L. Greatwall kinase participates in the Cdc2 autoregulatory loop in Xenopus egg extracts. Mol. Cell 22, 83–91 (2006).

    Article  CAS  PubMed  Google Scholar 

  110. Ferris, D. K., Maloid, S. C. & Li, C. C. Ubiquitination and proteasome mediated degradation of polo-like kinase. Biochem. Biophys. Res. Commun. 252, 340–344 (1998).

    Article  CAS  PubMed  Google Scholar 

  111. Engelbert, D., Schnerch, D., Baumgarten, A. & Wasch, R. The ubiquitin ligase APCCdh1 is required to maintain genome integrity in primary human cells. Oncogene 27, 907–917 (2008).

    Article  CAS  PubMed  Google Scholar 

  112. Garci-Higuera, I. et al. Genomic stability and tumour suppression by the APC/C cofactor Cdh1. Nature Cell Biol. 10, 802–811 (2008).

    Article  CAS  Google Scholar 

  113. Shirayama, M., Zachariae, W., Ciosk, R. & Nasmyth, K. The Polo-like kinase Cdc5p and the WD-repeat protein Cdc20p/fizzy are regulators and substrates of the anaphase promoting complex in Saccharomyces cerevisiae. EMBO J. 17, 1336–1349 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Charles, J. F. et al. The Polo-related kinase Cdc5 activates and is destroyed by the mitotic cyclin destruction machinery in S. cerevisiae. Curr. Biol. 8, 497–507 (1998).

    Article  CAS  PubMed  Google Scholar 

  115. Visintin, C. et al. APC/C–Cdh1-mediated degradation of the Polo kinase Cdc5 promotes the return of Cdc14 into the nucleolus. Genes Dev. 22, 79–90 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Yamashita, Y. et al. Sak serine–threonine kinase acts as an effector of Tec tyrosine kinase. J. Biol. Chem. 276, 39012–39020 (2001).

    Article  CAS  PubMed  Google Scholar 

  117. Zimmerman, W. C. & Erikson, R. L. Polo-like kinase 3 is required for entry into S phase. Proc. Natl Acad. Sci. USA 104, 1847–1852 (2007). A convincing case implicating human PLK3 in the promotion of S phase.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Cunha-Ferreira, I. et al. The SCF/Slimb ubiquitin ligase limits centrosome amplification through degradation of SAK/PLK4. Curr. Biol. 19, 43–49 (2009).

    Article  CAS  PubMed  Google Scholar 

  119. Seong, Y. S. et al. A spindle checkpoint arrest and a cytokinesis failure by the dominant-negative polo-box domain of Plk1 in U-2 OS cells. J. Biol. Chem. 277, 32282–32293 (2002).

    Article  CAS  PubMed  Google Scholar 

  120. Lee, K. S., Grenfell, T. Z., Yarm, F. R. & Erikson, R. L. Mutation of the polo-box disrupts localization and mitotic functions of the mammalian polo kinase Plk. Proc. Natl Acad. Sci. USA 95, 9301–9306 (1998). Well before the identification of the PBD as a phosphopeptide-binding unit, this paper shows that a Polo box of mouse PLK1 is essential for its ability to complement yeast cdc5 mutants and for its targeting to discrete subcellular structures, suggesting that Polo boxes might mediate protein interactions.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Archambault, V., D'Avino, P. P., Deery, M. J., Lilley, K. S. & Glover, D. M. Sequestration of Polo kinase to microtubules by phosphopriming-independent binding to Map205 is relieved by phosphorylation at a CDK site in mitosis. Genes Dev. 22, 2707–2720 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Lowery, D. M. et al. Proteomic screen defines the Polo-box domain interactome and identifies Rock2 as a Plk1 substrate. EMBO J. 26, 2262–2273 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. van de Weerdt, B. C. et al. Polo-box domains confer target specificity to the Polo-like kinase family. Biochim. Biophys. Acta 1783, 1015–1022 (2008).

    Article  CAS  PubMed  Google Scholar 

  124. Kothe, M. et al. Structure of the catalytic domain of human polo-like kinase 1. Biochemistry 46, 5960–5971 (2007).

    Article  CAS  PubMed  Google Scholar 

  125. Garcia-Alvarez, B., de Carcer, G., Ibanez, S., Bragado-Nilsson, E. & Montoya, G. Molecular and structural basis of polo-like kinase 1 substrate recognition: implications in centrosomal localization. Proc. Natl Acad. Sci. USA 104, 3107–3112 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Mirouse, V., Formstecher, E. & Couderc, J. L. Interaction between Polo and BicD proteins links oocyte determination and meiosis control in Drosophila. Development 133, 4005–4013 (2006).

    Article  CAS  PubMed  Google Scholar 

  127. Xiang, Y. et al. The inhibition of Polo kinase by matrimony maintains G2 arrest in the meiotic cell cycle. PLoS Biol. 5, e323 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  128. Nishi, Y., Rogers, E., Robertson, S. M. & Lin, R. Polo kinases regulate C. elegans embryonic polarity via binding to DYRK2-primed MEX-5 and MEX-6. Development 135, 687–697 (2008).

    Article  CAS  PubMed  Google Scholar 

  129. Rivers, D. M., Moreno, S., Abraham, M. & Ahringer, J. PAR proteins direct asymmetry of the cell cycle regulators Polo-like kinase and Cdc25. J. Cell Biol. 180, 877–885 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Budirahardja, Y. & Gonczy, P. PLK-1 asymmetry contributes to asynchronous cell division of C. elegans embryos. Development 135, 1303–1313 (2008).

    Article  CAS  PubMed  Google Scholar 

  131. Wang, H., Ouyang, Y., Somers, W. G., Chia, W. & Lu, B. Polo inhibits progenitor self-renewal and regulates Numb asymmetry by phosphorylating Pon. Nature 449, 96–100 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Wang, H. et al. Aurora-A acts as a tumor suppressor and regulates self-renewal of Drosophila neuroblasts. Genes Dev. 20, 3453–3463 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Seeburg, D. P., Pak, D. & Sheng, M. Polo-like kinases in the nervous system. Oncogene 24, 292–298 (2005).

    Article  CAS  PubMed  Google Scholar 

  134. Seeburg, D. P., Feliu-Mojer, M., Gaiottino, J., Pak, D. T. & Sheng, M. Critical role of CDK5 and Polo-like kinase 2 in homeostatic synaptic plasticity during elevated activity. Neuron 58, 571–583 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Myer, D. L., Bahassi el, M. & Stambrook, P. J. The Plk3–Cdc25 circuit. Oncogene 24, 299–305 (2005).

    Article  CAS  PubMed  Google Scholar 

  136. Xie, S. et al. Plk3 functionally links DNA damage to cell cycle arrest and apoptosis at least in part via the p53 pathway. J. Biol. Chem. 276, 43305–43312 (2001).

    Article  CAS  PubMed  Google Scholar 

  137. Bahassi el, M. et al. Mammalian Polo-like kinase 3 (Plk3) is a multifunctional protein involved in stress response pathways. Oncogene 21, 6633–6640 (2002).

    Article  PubMed  CAS  Google Scholar 

  138. Matthew, E. M. et al. Replication stress, defective S-phase checkpoint and increased death in Plk2-deficient human cancer cells. Cell Cycle 6, 2571–2578 (2007).

    Article  CAS  PubMed  Google Scholar 

  139. Swallow, C. J., Ko, M. A., Siddiqui, N. U., Hudson, J. W. & Dennis, J. W. Sak/Plk4 and mitotic fidelity. Oncogene 24, 306–312 (2005).

    Article  CAS  PubMed  Google Scholar 

  140. Morgan, D. O. The Cell Cycle: Principles of Control (New Science, London, 2007).

  141. D'Amours, D. & Amon, A. At the interface between signaling and executing anaphase — Cdc14 and the FEAR network. Genes Dev. 18, 2581–2595 (2004).

    Article  CAS  PubMed  Google Scholar 

  142. Jang, Y. J., Lin, C. Y., Ma, S., Erikson, R. L. Functional studies on the role of the C-terminal domain of mammalian polo-like kinase. Proc. Natl Acad. Sci. USA 99, 1984–1989 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We apologize to the authors of hundreds of original and significant papers that could not be cited because of space constraints. V.A. is supported by a Long-Term Fellowship from the Human Frontier Science Program. Research on Polo-like kinases in the Glover laboratory is supported by Cancer Research UK, the Medical Research Council and the Biotechnology and Biological Sciences Research Council.

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  1. Department of Genetics, Cancer Research UK Cell Cycle Genetics Research Group, University of Cambridge, Downing Street, Cambridge, CB2 3EH, UK

    Vincent Archambault & David M. Glover

  2. Vincent Archambault & David M. Glover

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Glossary

Cytokinesis

The process of cytoplasmic division in eukaryotic cells that gives rise to two daughter cells.

Centriole

A short, barrel-like array of microtubules at the centre of centrosomes, which organizes the organelle.

Spindle pole body

The yeast equivalent of the centrosome.

Cell cycle checkpoint

A control mechanism that ensures the fidelity of cell division in eukaryotic cells. A checkpoint verifies whether the processes at each phase of the cell cycle have been accurately completed before progression into the next phase.

Microtubule-organizing centre

(MTOC). A structure that nucleates and organizes microtubules. MTOCs include animal centrosomes and yeast spindle pole bodies.

Basal body

An organelle formed from a centriole. The basal body is found at the base of a eukaryotic cilium or flagellum, and serves as a nucleation site for the growth of axoneme microtubules.

Centromere

The region of a chromosome in which sister chromatid cohesion is preserved until anaphase onset and where a kinetochore is assembled.

Kinetochore

A multiprotein complex that assembles on centromeric DNA and mediates the attachment and movement of chromosomes along the microtubules of the mitotic spindle.

Central spindle

The central group of microtubules that extend uninterrupted between the spindle poles.

Imaginal disc

A single-cell layer epithelial structure of the Drosophila melanogaster larva that gives rise to wings, legs and other appendages.

T-loop

A structural loop that is highly conserved in the catalytic domains of protein kinases. Phosphorylation of this transactivation loop is often required for full catalytic activity.

Proteasome

A large protein complex that is responsible for degrading intracellular proteins that have been targeted for destruction, usually by the addition of ubiquitin polymers.

SCF ubiquitin ligase

A multisubunit ubiquitin ligase that contains SKP1, a member of the cullin family (CUL1) and an F-box-containing protein, as well as a RING-finger-containing protein (ROC1 or RBX1).

Midbody

A microtubule-containing structure that is derived from the central spindle and that persists at the end of animal cell division, just before the complete separation of the dividing cells.

Germinal vesicular breakdown

Nuclear envelope breakdown at the beginning of meiosis I.

Dendritic spine

A small, membranous protrusion from neuronal dendrites that receives input from a single synapse of an axon.

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Archambault, V., Glover, D. Polo-like kinases: conservation and divergence in their functions and regulation. Nat Rev Mol Cell Biol 10, 265–275 (2009). https://doi.org/10.1038/nrm2653

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