Antiviral action of the tumor suppressor ARF
Open Access
- 7 September 2006
- journal article
- research article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 25 (18), 4284-4292
- https://doi.org/10.1038/sj.emboj.7601302
Abstract
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
This publication has 59 references indexed in Scilit:
- Senescence in premalignant tumoursNature, 2005
- p19 Arf Suppresses Growth, Progression, and Metastasis of Hras-Driven Carcinomas through p53-Dependent and -Independent PathwaysPLoS Biology, 2004
- Different Requirements for the Cytostatic and Apoptotic Effects of Type I InterferonsPublished by Elsevier BV ,2004
- Functional and Physical Interaction of the Human ARF Tumor Suppressor with Tat-binding Protein-1Published by Elsevier BV ,2004
- Pondering the Promyelocytic Leukemia Protein (PML) Puzzle: Possible Functions for PML Nuclear BodiesMolecular and Cellular Biology, 2002
- The Nucleolar Phosphoprotein B23 Interacts with Hepatitis Delta Antigens and Modulates the Hepatitis Delta Virus RNA ReplicationPublished by Elsevier BV ,2001
- Association of p19ARF with Mdm2 inhibits ubiquitin ligase activity of Mdm2 for tumor suppressor p53The EMBO Journal, 1999
- p53 and tumour viruses: Catching the guardian off-guardTrends in Microbiology, 1997
- Interferon‐Modulated Expression of Genes Encoding the Nuclear‐Dot‐Associated Proteins Sp100 and Promyelocytic Leukemia Protein (PML)JBIC Journal of Biological Inorganic Chemistry, 1996
- Cell Cycle Phase-Dependent Changes of Localization and Oligomerization States of Nucleophosmin / B23Biochemical and Biophysical Research Communications, 1995