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Phase separation of Polo-like kinase 4 by autoactivation and clustering drives centriole biogenesis

Author

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  • Jung-Eun Park

    (National Institutes of Health)

  • Liang Zhang

    (National Institutes of Health)

  • Jeong Kyu Bang

    (Korea Basic Science Institute)

  • Thorkell Andresson

    (Frederick National Laboratory for Cancer Research and Leidos Biomedical Research Inc.)

  • Frank DiMaio

    (University of Washington)

  • Kyung S. Lee

    (National Institutes of Health)

Abstract

Tight control of centriole duplication is critical for normal chromosome segregation and the maintenance of genomic stability. Polo-like kinase 4 (Plk4) is a key regulator of centriole biogenesis. How Plk4 dynamically promotes its symmetry-breaking relocalization and achieves its procentriole-assembly state remains unknown. Here we show that Plk4 is a unique kinase that utilizes its autophosphorylated noncatalytic cryptic polo-box (CPB) to phase separate and generate a nanoscale spherical condensate. Analyses of the crystal structure of a phospho-mimicking, condensation-proficient CPB mutant reveal that a disordered loop at the CPB PB2-tip region is critically required for Plk4 to generate condensates and induce procentriole assembly. CPB phosphorylation also promotes Plk4’s dissociation from the Cep152 tether while binding to downstream STIL, thus allowing Plk4 condensate to serve as an assembling body for centriole biogenesis. This study uncovers the mechanism underlying Plk4 activation and may offer strategies for anti-Plk4 intervention against genomic instability and cancer.

Suggested Citation

  • Jung-Eun Park & Liang Zhang & Jeong Kyu Bang & Thorkell Andresson & Frank DiMaio & Kyung S. Lee, 2019. "Phase separation of Polo-like kinase 4 by autoactivation and clustering drives centriole biogenesis," Nature Communications, Nature, vol. 10(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12619-2
    DOI: 10.1038/s41467-019-12619-2
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    Cited by:

    1. Jung-Eun Park & Tae-Sung Kim & Yan Zeng & Melissa Mikolaj & Jong Ahn & Muhammad S. Alam & Christina M. Monnie & Victoria Shi & Ming Zhou & Tae-Wook Chun & Frank Maldarelli & Kedar Narayan & Jinwoo Ahn, 2024. "Centrosome amplification and aneuploidy driven by the HIV-1-induced Vpr•VprBP•Plk4 complex in CD4+ T cells," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. Niccolò Banterle & Adrian P. Nievergelt & Svenja Buhr & Georgios N. Hatzopoulos & Charlène Brillard & Santiago Andany & Tania Hübscher & Frieda A. Sorgenfrei & Ulrich S. Schwarz & Frauke Gräter & Geor, 2021. "Kinetic and structural roles for the surface in guiding SAS-6 self-assembly to direct centriole architecture," Nature Communications, Nature, vol. 12(1), pages 1-14, December.

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