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Polo‐like kinase‐1 triggers histone phosphorylation by Haspin in mitosis

Linli Zhou, Xiaoying Tian, Cailei Zhu, Fangwei Wang, Jonathan MG Higgins

Author Affiliations

  1. Linli Zhou1,,
  2. Xiaoying Tian1,,
  3. Cailei Zhu2,
  4. Fangwei Wang*,1 and
  5. Jonathan MG Higgins*,2,3
  1. 1Life Sciences Institute and Innovation Center for Cell Biology, Zhejiang University, Hangzhou, Zhejiang Province, China
  2. 2Division of Rheumatology, Immunology and Allergy, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA
  3. 3Institute for Cell and Molecular Biosciences The Medical School, Newcastle University, Newcastle‐upon‐Tyne, UK
  1. * Corresponding author. Tel: +86 571 88206127; Fax: +86 571 88206127; E‐mail: fwwang{at}zju.edu.cn

    Corresponding author. Tel: +1 617 525 1101; Fax: +1 617 525 1010; E‐mails: jhiggins{at}rics.bwh.harvard.edu or jonathan.higgins{at}ncl.ac.uk

  1. These authors contributed equally to this work.

  2. Author contributions

    LZ, XT, CZ, FW and JMGH carried out the experiments. FW and JMGH conceived and directed the project and wrote the paper.

Abstract

Histone modifications coordinate the chromatin localization of key regulatory factors in mitosis. For example, mitotic phosphorylation of Histone H3 threonine‐3 (H3T3ph) by Haspin creates a binding site for the chromosomal passenger complex (CPC). However, how these histone modifications are spatiotemporally controlled during the cell cycle is unclear. Here we show that Plk1 binds to Haspin in a Cdk1‐phosphorylation‐dependent manner. Reducing Plk1 activity decreases the phosphorylation of Haspin and inhibits H3T3ph, particularly in prophase, suggesting that Plk1 is required for initial activation of Haspin in early mitosis. These studies demonstrate that Plk1 can positively regulate CPC recruitment in mitosis.

Synopsis

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During mitosis, Haspin phosphorylates histone H3 at Thr 3 to recruit the chromosomal passenger complex (CPC). This study shows that this event is controlled by Plk1‐mediated phosphorylation of Haspin, which is required for H3 modification in early mitosis and thus for appropriate CPC recruitment.

  • Priming phosphorylation of Haspin by Cdk1‐Cyclin B promotes Plk1 binding

  • Plk1 interacts with the S‐pT128‐P motif of Haspin

  • Phosphorylation of Haspin by Plk1 stimulates histone H3 phosphorylation at Thr 3, particularly in early mitosis

  • Plk1 has a positive role in recruiting the CPC to centromeres

Footnotes

  • Conflict of interest

    The authors declare that they have no conflict of interest.

  • Received October 7, 2013.
  • Revision received December 9, 2013.
  • Accepted December 10, 2013.

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