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  • The EMBO Journal (2006) 25, 4284 - 4292
  • doi:10.1038/sj.emboj.7601302

Published online: 7 September 2006

Antiviral action of the tumor suppressor ARF

María A García1, Manuel Collado2, César Muñoz-Fontela3,a, Ander Matheu2, Laura Marcos-Villar3, Javier Arroyo3, Mariano Esteban1, Manuel Serrano2 and Carmen Rivas3

  1. Centro Nacional de Biotecnología (CNB), Universidad Autónoma de Madrid, Madrid, Spain
  2. Spanish National Cancer Centre (CNIO), 3 Melchor Fernández Almagro, Madrid, Spain
  3. Departamento de Microbiología II, Universidad Complutense de Madrid (UCM), Plaza Ramón y Cajal s/n, Madrid, Spain

Correspondence to:

Manuel Serrano, Spanish National Cancer Center (CNIO), 3 Melchor Fernández Almagro, Madrid 28029, Spain. Tel.: +34 91 7328032; Fax: +34 91 7328028; E-mail: mserrano@cnio.es

aPresent address: Department of Oncological Sciences, Mount Sinai School of Medicine, One Gustave L Levy Place, NY 10029, USA

Received 10 June 2006; Accepted 27 July 2006

Oncogenic viruses frequently target the pathways controlled by tumor suppressor genes, suggesting an extra function for these proteins as antiviral factors. The control exerted by the tumor suppressor Arf on cellular proliferation is crucial to restrict tumor development; however, a potential contribution of Arf to prevent viral infectivity has remained unexplored. In the present study, we investigated the consequences of loss or increased expression of Arf on viral infection. Our results reveal that ARF expression is induced by interferon and after viral infection. Furthermore, we show that ARF protects against viral infection in a gene dosage-dependent manner, and that this antiviral action is mediated in part by PKR through a mechanism that involves ARF-induced release of PKR from nucleophosmin complexes. Finally, Arf-null mice were hypersensitive to viral infection compared to wild-type mice. Together, our results reveal a novel and unexpected role for the tumor suppressor ARF in viral infection surveillance.

  • Keywords:

    • antiviral activity,
    • IFN,
    • ARF,
    • NPM,
    • PKR