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Phosphorylation of Plk1 at Ser326 regulates its functions during mitotic progression

Oncogene volume 27, pages 6635–6645 (2008)Cite this article

Abstract

Polo-like kinase 1 (Plk1), the best characterized member of the mammalian polo-like kinase family, is well regulated throughout the cell cycle at the protein expression level. Moreover, it is known that Plk1 kinase activity is also regulated at the post-translational level through phosphorylation. However, the upstream kinases of Plk1 have not been identified. Although the involvement of the p38 MAP kinase pathway in cellular responses to stress has been well documented, the role of this pathway in normal cell cycle progression is unclear. Here, we show that phosphorylated p38 and MAP kinase-activated protein kinase 2 (MK2) are colocalized with Plk1 to the spindle poles during prophase and metaphase. Specific depletion of various members of the p38 MAP kinase pathway by the use of RNA interference revealed that the pathway is required for mitotic progression under normal growth conditions. Furthermore, MK2 directly phosphorylates Ser326 of Plk1. Ectopic expression of Plk1-S326A completely blocked cells at mitosis, likely due to the defect of bipolar spindle formation and subsequent activation of the spindle checkpoint. Only Plk1-S326E, but not the Plk1-S326A, efficiently rescued the p38 or MK2-depletion-induced mitotic defects, further solidifying the requirement of S326 phosphorylation during mitotic progression.

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Accession codes

Accessions

GenBank/EMBL/DDBJ

Abbreviations

MK2:

MAP kinase-activated protein kinase 2

Plk1:

polo-like kinase 1

RNAi:

RNA interference

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Acknowledgements

We are grateful to Dr Raymond Erikson, in whose laboratory the preliminary experiments were performed, for generously providing many cell lines and plasmids. We appreciate Eleanor Erikson, Xiaoyi Zhang and Hongchang Li for helpful discussions and critical reading of the paper. XL is a recipient of the Howard Temin Award from the National Cancer Institute (K01 CA114401).

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Authors and Affiliations

  1. Department of Biochemistry and the Cancer Center, Purdue University, West Lafayette, IN, USA

    J Tang, X Yang & X Liu

  2. Department of Chemistry, Sichuan University, Chengdu, Sichuan, PR China

    X Yang

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  1. J Tang
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Correspondence to X Liu.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Tang, J., Yang, X. & Liu, X. Phosphorylation of Plk1 at Ser326 regulates its functions during mitotic progression. Oncogene 27, 6635–6645 (2008). https://doi.org/10.1038/onc.2008.262

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