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APC/C is an essential regulator of centrosome clustering

Author

Listed:
  • Konstantinos Drosopoulos

    (Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research)

  • Chan Tang

    (Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research
    Present address: Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Archimedesweg 4-6, Leiden 2333 CN, The Netherlands)

  • William C. H. Chao

    (Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research
    Present address: London Research Institute, Cancer Research UK, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3LY, UK)

  • Spiros Linardopoulos

    (Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research
    Cancer Research UK, Cancer Therapeutics Unit, The Institute of Cancer Research)

Abstract

Centrosome amplification has been extensively associated with cancer. Cancer cells with extra centrosomes have the ability to cluster the extra centrosomes and divide in a bipolar fashion. Although a number of proteins have been shown to be involved in centrosome clustering, a mechanistic understanding of how this process is coordinated is not yet well defined. Here, to reveal regulators of centrosome clustering, we perform small interfering RNA (siRNA) screens with multiple assay readouts in a human isogenic cellular model. We find that APC/C activity is essential for centrosome clustering. We show that the motor kinesin Eg5 is a substrate of APC/C-CDH1, and that inhibition of APC/C results in stabilization of Eg5. Increased Eg5 protein levels disturb the balance of forces on the spindle and prevent centrosome clustering. This process is completely reversed after a short treatment with the Eg5 inhibitor, monastrol. These data advance our understanding of the regulation of centrosome clustering.

Suggested Citation

  • Konstantinos Drosopoulos & Chan Tang & William C. H. Chao & Spiros Linardopoulos, 2014. "APC/C is an essential regulator of centrosome clustering," Nature Communications, Nature, vol. 5(1), pages 1-13, September.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4686
    DOI: 10.1038/ncomms4686
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    1. Fijnanda van Klingeren & Vincent Buskens, 2024. "Graduated sanctioning, endogenous institutions and sustainable cooperation in common-pool resources: An experimental test," Rationality and Society, , vol. 36(2), pages 183-229, May.

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