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RNA polymerase II transcription is required for human papillomavirus type 16 E7- and hydroxyurea-induced centriole overduplication

Oncogene volume 26, pages 215–223 (2007)Cite this article

Abstract

Aberrant centrosome numbers are detected in virtually all human cancers where they can contribute to chromosomal instability by promoting mitotic spindle abnormalities. Despite their widespread occurrence, the molecular mechanisms that underlie centrosome amplification are only beginning to emerge. Here, we present evidence for a novel regulatory circuit involved in centrosome overduplication that centers on RNA polymerase II (pol II). We found that human papillomavirus type 16 E7 (HPV-16 E7)- and hydroxyurea (HU)-induced centriole overduplication are abrogated by α-amanitin, a potent and specific RNA pol II inhibitor. In contrast, normal centriole duplication proceeded undisturbed in α-amanitin-treated cells. Centriole overduplication was significantly reduced by siRNA-mediated knock down of CREB-binding protein (CBP), a transcriptional co-activator. We identified cyclin A2 as a key transcriptional target of RNA pol II during HU-induced centriole overduplication. Collectively, our results show that ongoing RNA pol II transcription is required for centriole overduplication whereas it may be dispensable for normal centriole duplication. Given that many chemotherapeutic agents function through inhibition of transcription, our results may help to develop strategies to target centrosome-mediated chromosomal instability for cancer therapy and prevention.

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Acknowledgements

We are grateful to Michel Bornens, Karl Münger and Jeffrey L Salisbury for sharing important reagents and William Saunders for helpful suggestions. This work was supported by Public Health Service Grant NIH/NCI R01 CA112598 (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, N Spardy, M Tseng, J-A Kwon, X Teng & S Duensing

  3. Biochemistry and Molecular Genetics Graduate Program, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    N Spardy & K Bartoli

  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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Duensing, A., Liu, Y., Spardy, N. et al. RNA polymerase II transcription is required for human papillomavirus type 16 E7- and hydroxyurea-induced centriole overduplication. Oncogene 26, 215–223 (2007). https://doi.org/10.1038/sj.onc.1209782

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