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Emerging roles of DNA tumor viruses in cell proliferation: new insights into genomic instability

Oncogene volume 22, pages 6508–6516 (2003)Cite this article

Abstract

The small DNA virus proteins E1A and E1B from human Adenovirus, E6 and E7 from human papillomavirus, and large T and small T antigens from SV40, are multifaceted molecular tools that can carry out an impressive number of tasks in the host cell. These viral factors, collectively termed ‘oncoproteins’ for their ability to induce cancer, can be viewed as paradigmatic oncogenic factors which can disrupt checkpoint controls at multiple levels – they interfere with both ‘gatekeeper’ cellular functions, including major control pathways of cell cycle and apoptosis, and with ‘caretaker’ functions, thereby inducing mitotic abnormalities and increasing genomic instability. Both E1A and E7 have been recently found to interact physically with the Ran GTPase. This interaction is key in uncoupling the centrosome cycle from the cell cycle, highlighting a direct link between viral infection and the induction of genomic instability. Further expanding our current knowledge in this field will be crucial to elucidate viral strategies leading to cellular transformation and cancer progression, as well as design novel preventive or therapeutic approaches to human cancer.

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Acknowledgements

Research in our laboratories was supported by Associazione Italiana per la Ricerca sul Cancro (AIRC), Agenzia Spaziale Italiana (ASI) and Ministero della Salute grants to MGP and PL.

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Authors and Affiliations

  1. Institute of Molecular Biology and Pathology, CNR National Research Council, Rome, Italy

    Patrizia Lavia

  2. Regina Elena Cancer Institute, Center for Experimental Research, Rome, Italy

    Anna Maria Mileo & Marco G Paggi

  3. Department of Biotechnology, Temple University, Philadelphia, PA, USA

    Antonio Giordano

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  1. Patrizia Lavia
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  2. Anna Maria Mileo
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  4. Marco G Paggi
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Correspondence to Marco G Paggi.

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While this review was in preparation, it has been shown that a fraction of the Ran GTPase itself is tightly associated to centrosomes (Keryer G, Di Fiore B, Celati C, Lechtreck KF, Mogensen M, Delouvée M, Lavia P, Bornens M and Tassin AM (2003) Mol. Biol. Cell, in press).

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Lavia, P., Mileo, A., Giordano, A. et al. Emerging roles of DNA tumor viruses in cell proliferation: new insights into genomic instability. Oncogene 22, 6508–6516 (2003). https://doi.org/10.1038/sj.onc.1206861

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