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Complex formation of Plk1 and INCENP required for metaphase–anaphase transition

Nature Cell Biology volume 8, pages 180–187 (2006)Cite this article

An Erratum to this article was published on 01 February 2006

Abstract

Mitotic chromosomal dynamics is regulated by the coordinated activities of many mitotic kinases1, such as cyclin-dependent kinase 1 (Cdk1)2,3, Aurora-B4 or Polo-like kinase 1 (Plk1)5, but the mechanisms of their coordination remain unknown. Here, we report that Cdk1 phosphorylates Thr 59 and Thr 388 on inner centromere protein (INCENP), which regulates the localization4 and kinase activity6,7,8 of Aurora-B from prophase to metaphase. INCENP depletion disrupts Plk1 localization specifically at the kinetochore. This phenotype is rescued by the exogenous expression of INCENP wild type and INCENP mutated at Thr 59 to Ala (T59A), but not at Thr 388 to Ala (T388A). The replacement of endogenous INCENP with T388A resulted in the delay of progression from metaphase to anaphase. We propose that INCENP phosphorylation by Cdk1 is necessary for the recruitment of Plk1 to the kinetochore, and that the complex formation of Plk1 and Aurora-B on INCENP may play crucial roles in the regulation of chromosomal dynamics.

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Figure 1: INCENP phosphorylation by Cdk1.
Figure 2: Spatial and temporal localization of each INCENP phosphorylation.
Figure 3: Recruitment of Plk1 to the kinetochore via INCENP.
Figure 4: Requirement for phosphorylation of INCENP at Thr 388 in Plk1 recruitment to the kinetochore.
Figure 5: Function of INCENP phosphorylation at Thr 388 by Cdk1.

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Acknowledgements

The authors thank T. Yamaguchi, T. Yokoyama and Y. Hayashi for technical assistance and H. Masumoto for providing anti-centromere antibody (ACA). We are grateful to H. Silljé, A. Hanisch, A. Uldschmid and other members of the Max-Planck Institute for Biochemistry for providing pGEX vectors carrying PBD and for helpful discussions. We also thank M. Ohara for language assistance. This work was supported in part by Grants-in-Aid for Scientific Research and Cancer Research from the Ministry of Education, Science, Technology, Sports, and Culture of Japan; by a grant-in-aid for the Third Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health and Welfare, Japan; by The Naito Foundation; and by the Uehara Memorial Foundation.

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Authors and Affiliations

  1. Division of Biochemistry, Aichi Cancer Center Research Institute, Nagoya, 464-8681, Aichi, Japan

    Hidemasa Goto, Aie Kawajiri & Masaki Inagaki

  2. Virology Division, National Cancer Center Research Institute, Chuo-ku, Tokyo, 104-0045, Japan

    Tohru Kiyono

  3. Division of Molecular and Cell Biology, Shigei Medical Research Institute, Okayama, 701-0202, Okayama, Japan

    Yasuko Tomono

  4. Department of Biochemistry II, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Aichi, Japan

    Takeshi Urano & Koichi Furukawa

  5. Department of Cell Biology, Max-Planck Institute for Biochemistry, Martinstried, D-82152, Germany

    Erich A. Nigg

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Goto, H., Kiyono, T., Tomono, Y. et al. Complex formation of Plk1 and INCENP required for metaphase–anaphase transition. Nat Cell Biol 8, 180–187 (2006). https://doi.org/10.1038/ncb1350

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