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

  1. Author:
    Park, Jung-Eun [ORCID]
    Zhang, Liang [ORCID]
    Bang, Jeong Kyu [ORCID]
    Andresson,Thorkell
    DiMaio, Frank
    Lee, Kyung S [ORCID]

  2. Author Address

    Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD, 20892, USA., Division of Magnetic Resonance, Korea Basic Science Institute, 162 Yeongudanji-ro, Ochang-eup, Cheongju, 28119, Republic of Korea., Protein Characterization Laboratory, Frederick National Laboratory for Cancer Research and Leidos Biomedical Research Inc., 8560 Progress Drive, Frederick, MD, 21702, USA., Department of Biochemistry and Institute for Protein Design, University of Washington, 1705 NE Pacific Street, Seattle, WA, 98195, USA., Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD, 20892, USA. kyunglee@mail.nih.gov.,
    1. Year: 2019
    2. Date: Oct 31
    3. Epub Date: 2019 10 31
  2. Journal: Nature communications
    1. 10
    2. 1
    3. Pages: 4959
  4. Type of Article: Article
  5. Article Number: 4959
  6. ISSN: 2041-1723
  1. 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 39;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.

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External Sources

  1. View Full Text
  2. DOI: 10.1038/s41467-019-12619-2
  3. PMID: 31672968
  4. View record in Web of Science®
  5. WOS: 000493438700007
  6. PII : 10.1038/s41467-019-12619-2

Library Notes

  1. Fiscal Year: FY2019-2020
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