APC/C is an essential regulator of centrosome clustering

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 understand...

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Veröffentlicht in:Nature communications 2014-04, Vol.5 (1), p.3686-3686, Article 3686
Hauptverfasser: Drosopoulos, Konstantinos, Tang, Chan, Chao, William C. H., Linardopoulos, Spiros
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Sprache:eng
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Zusammenfassung: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. Cells with multiple centrosomes, as are often observed in cancer, can still divide successfully because the centrosomes cluster to form a single spindle pole body. Drosopoulos et al. show that degradation of the kinesin Eg5 by APC/C-CDH1 is required for centrosome clustering.
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms4686