Cargando…

Transcriptional role of p53 in interferon-mediated antiviral immunity

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Muñoz-Fontela, César, Macip, Salvador, Martínez-Sobrido, Luis, Brown, Lauren, Ashour, Joseph, García-Sastre, Adolfo, Lee, Sam W., Aaronson, Stuart A.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2525597/
https://www.ncbi.nlm.nih.gov/pubmed/18663127
http://dx.doi.org/10.1084/jem.20080383
_version_ 1782158671424258048
author Muñoz-Fontela, César
Macip, Salvador
Martínez-Sobrido, Luis
Brown, Lauren
Ashour, Joseph
García-Sastre, Adolfo
Lee, Sam W.
Aaronson, Stuart A.
author_facet Muñoz-Fontela, César
Macip, Salvador
Martínez-Sobrido, Luis
Brown, Lauren
Ashour, Joseph
García-Sastre, Adolfo
Lee, Sam W.
Aaronson, Stuart A.
author_sort Muñoz-Fontela, César
collection PubMed
description 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.
format Text
id pubmed-2525597
institution National Center for Biotechnology Information
language English
publishDate 2008
publisher The Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-25255972009-02-04 Transcriptional role of p53 in interferon-mediated antiviral immunity Muñoz-Fontela, César Macip, Salvador Martínez-Sobrido, Luis Brown, Lauren Ashour, Joseph García-Sastre, Adolfo Lee, Sam W. Aaronson, Stuart A. J Exp Med Brief Definitive Reports 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. The Rockefeller University Press 2008-08-04 /pmc/articles/PMC2525597/ /pubmed/18663127 http://dx.doi.org/10.1084/jem.20080383 Text en © 2008 Muñoz-Fontela et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Brief Definitive Reports
Muñoz-Fontela, César
Macip, Salvador
Martínez-Sobrido, Luis
Brown, Lauren
Ashour, Joseph
García-Sastre, Adolfo
Lee, Sam W.
Aaronson, Stuart A.
Transcriptional role of p53 in interferon-mediated antiviral immunity
title Transcriptional role of p53 in interferon-mediated antiviral immunity
title_full Transcriptional role of p53 in interferon-mediated antiviral immunity
title_fullStr Transcriptional role of p53 in interferon-mediated antiviral immunity
title_full_unstemmed Transcriptional role of p53 in interferon-mediated antiviral immunity
title_short Transcriptional role of p53 in interferon-mediated antiviral immunity
title_sort transcriptional role of p53 in interferon-mediated antiviral immunity
topic Brief Definitive Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2525597/
https://www.ncbi.nlm.nih.gov/pubmed/18663127
http://dx.doi.org/10.1084/jem.20080383
work_keys_str_mv AT munozfontelacesar transcriptionalroleofp53ininterferonmediatedantiviralimmunity
AT macipsalvador transcriptionalroleofp53ininterferonmediatedantiviralimmunity
AT martinezsobridoluis transcriptionalroleofp53ininterferonmediatedantiviralimmunity
AT brownlauren transcriptionalroleofp53ininterferonmediatedantiviralimmunity
AT ashourjoseph transcriptionalroleofp53ininterferonmediatedantiviralimmunity
AT garciasastreadolfo transcriptionalroleofp53ininterferonmediatedantiviralimmunity
AT leesamw transcriptionalroleofp53ininterferonmediatedantiviralimmunity
AT aaronsonstuarta transcriptionalroleofp53ininterferonmediatedantiviralimmunity