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Centriole overduplication through the concurrent formation of multiple daughter centrioles at single maternal templates

Oncogene volume 26, pages 6280–6288 (2007)Cite this article

Abstract

Abnormal centrosome numbers are detected in virtually all cancers. The molecular mechanisms that underlie centrosome amplification, however, are poorly characterized. Based on the model that each maternal centriole serves as a template for the formation of one and only one daughter centriole per cell division cycle, the prevailing view is that centriole overduplication arises from successive rounds of centriole reproduction. Here, we provide evidence that a single maternal centriole can concurrently generate multiple daughter centrioles. This mechanism was initially identified in cells treated with the peptide vinyl sulfone proteasome inhibitor Z-L3VS. We subsequently found that the formation of more than one daughter at maternal centrioles requires cyclin E/cyclin-dependent kinase 2 as well as Polo-like kinase 4 and that overexpression of these proteins mimics this phenotype in the absence of a proteasome inhibitor. Moreover, we show that the human papillomavirus type 16 E7 oncoprotein stimulates aberrant daughter centriole numbers in part through the formation of more than one daughter centriole at single maternal templates. These results help to explain how oncogenic stimuli can rapidly induce abnormal centriole numbers within a single cell-division cycle and provide insights into the regulation of centriole duplication.

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Acknowledgements

We thank Michel Bornens, William R Brinkley, Philip W Hinds, Karl Münger, Jeffrey L Salisbury and Jens Westendorf for sharing important reagents and/or helpful suggestions. We are grateful to Joseph Suhan for invaluable help and support with electron microscopy. We thank Huib Ovaa for helpful discussions. This work was supported by NIH/NCI grant R01 CA112598, the Susan G Komen Breast Cancer Foundation and a Research Scholar Grant from the American Cancer Society (to SD).

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Authors and Affiliations

  1. Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    A Duensing

  2. Molecular Virology Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA

    A Duensing, Y Liu, S A Perdreau & S Duensing

  3. Department of Cell Biology, Max Planck Institute of Biochemistry, Martinsried, Germany

    J Kleylein-Sohn & E A Nigg

  4. Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    S Duensing

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  1. A Duensing
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Correspondence to S Duensing.

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

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Duensing, A., Liu, Y., Perdreau, S. et al. Centriole overduplication through the concurrent formation of multiple daughter centrioles at single maternal templates. Oncogene 26, 6280–6288 (2007). https://doi.org/10.1038/sj.onc.1210456

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