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The Polo kinase Plk4 functions in centriole duplication

Abstract

The human Polo-like kinase 1 (PLK1) and its functional homologues that are present in other eukaryotes have multiple, crucial roles in meiotic and mitotic cell division1,2. By contrast, the functions of other mammalian Polo family members remain largely unknown. Plk4 is the most structurally divergent Polo family member; it is maximally expressed in actively dividing tissues and is essential for mouse embryonic development3. Here, we identify Plk4 as a key regulator of centriole duplication. Both gain- and loss-of-function experiments demonstrate that Plk4 is required — in cooperation with Cdk2, CP110 and Hs-SAS6 — for the precise reproduction of centrosomes during the cell cycle. These findings provide an attractive explanation for the crucial function of Plk4 in cell proliferation and have implications for the role of Polo kinases in tumorigenesis.

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Figure 1: Plk4 localizes to centrioles.
Figure 2: Overexpression of Plk4 increases centriole numbers.
Figure 3: Induction of putative centriole precursor material by Plk4.
Figure 4: Depletion of Plk4 causes progressive reduction in centriole numbers.
Figure 5: Cooperation of Plk4 with proteins implicated in centrosome duplication.

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Acknowledgements

We thank M. Bornens (Curie Institute, Paris) for the kind gift of HeLa cells expressing eGFP–centrin; and X. Yan and M. Casenghi for helpful advice and comments. We also thank J. Dennis, M. Ko and C. Swallow (Samuel Lunenfeld Institute, University of Toronto) for open discussions and for sharing results prior to publication. This work was supported by the Max-Planck Society, the Fonds der Chemischen Industrie and the Deutsche Forschungsgemeinschaft (SFB413).

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Correspondence to Erich A. Nigg.

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Habedanck, R., Stierhof, YD., Wilkinson, C. et al. The Polo kinase Plk4 functions in centriole duplication. Nat Cell Biol 7, 1140–1146 (2005). https://doi.org/10.1038/ncb1320

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