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Publication : Antiviral action of the tumor suppressor ARF.

First Author  García MA Year  2006
Journal  EMBO J Volume  25
Issue  18 Pages  4284-92
PubMed ID  16957780 Mgi Jnum  J:144668
Mgi Id  MGI:3831487 Doi  10.1038/sj.emboj.7601302
Citation  Garcia MA, et al. (2006) Antiviral action of the tumor suppressor ARF. EMBO J 25(18):4284-92
abstractText  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.
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