Transcriptional Role of p53 in Interferon-Mediated Antiviral Immunity

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Transcriptional Role of p53 in Interferon-Mediated Antiviral Immunity

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dc.contributor.author Muñoz-Fontela, César
dc.contributor.author Macip, Salvador
dc.contributor.author Martínez-Sobrido, Luis
dc.contributor.author Ashour, Joseph
dc.contributor.author García-Sastre, Adolfo
dc.contributor.author Aaronson, Stuart A.
dc.contributor.author Brown, Lauren
dc.contributor.author Lee, Sam Whan
dc.date.accessioned 2011-03-27T20:46:46Z
dc.date.issued 2008
dc.identifier.citation Muñoz-Fontela, César, Salvador Macip, Luis Martínez-Sobrido, Lauren Brown, Joseph Ashour, Adolfo García-Sastre, Sam W. Lee, and Stuart A. Aaronson. 2008. Transcriptional role of p53 in interferon-mediated antiviral immunity. Journal of Experimental Medicine 205(8): 1929-1938. en_US
dc.identifier.issn 0022-1007 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:4774198
dc.description.abstract Tumor suppressor p53 is activated by several stimuli, including DNA damage and oncogenic stress. Previous studies (Takaoka, A., S. Hayakawa, H. Yanai, D. Stoiber, H. Negishi, H. Kikuchi, S. Sasaki, K. Imai, T. Shibue, K. Honda, and T. Taniguchi. 2003. Nature. 424:516–523) have shown that p53 is also induced in response to viral infections as a downstream transcriptional target of type I interferon (IFN) signaling. Moreover, many viruses, including SV40, human papillomavirus, Kaposi's sarcoma herpesvirus, adenoviruses, and even RNA viruses such as polioviruses, have evolved mechanisms designated to abrogate p53 responses. We describe a novel p53 function in the activation of the IFN pathway. We observed that infected mouse and human cells with functional p53 exhibited markedly decreased viral replication early after infection. This early inhibition of viral replication was mediated both in vitro and in vivo by a p53-dependent enhancement of IFN signaling, specifically the induction of genes containing IFN-stimulated response elements. Of note, p53 also contributed to an increase in IFN release from infected cells. We established that this p53-dependent enhancement of IFN signaling is dependent to a great extent on the ability of p53 to activate the transcription of IFN regulatory factor 9, a central component of the IFN-stimulated gene factor 3 complex. Our results demonstrate that p53 contributes to innate immunity by enhancing IFN-dependent antiviral activity independent of its functions as a proapoptotic and tumor suppressor gene. en_US
dc.language.iso en_US en_US
dc.publisher Rockefeller University Press en_US
dc.relation.isversionof doi:10.1084/jem.20080383 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2525597/pdf/ en_US
dash.license LAA
dc.title Transcriptional Role of p53 in Interferon-Mediated Antiviral Immunity en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal Journal of Experimental Medicine en_US
dash.depositing.author Lee, Sam Whan
dc.date.available 2011-03-27T20:46:46Z
dash.affiliation.other HMS^Dermatology-Massachusetts General Hospital en_US

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