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dc.contributor.author | Granja, Aitor G. | - |
dc.contributor.author | Nogal París, María Luisa | - |
dc.contributor.author | Hurtado, Carolina | - |
dc.contributor.author | Águila, Carmen del | - |
dc.contributor.author | Carrascosa, Ángel L. | - |
dc.contributor.author | Salas Falgueras, María Luisa | - |
dc.contributor.author | Fresno, Manuel | - |
dc.contributor.author | Revilla Novella, Yolanda | - |
dc.date.accessioned | 2008-06-09T14:13:57Z | - |
dc.date.available | 2008-06-09T14:13:57Z | - |
dc.date.issued | 2006-01 | - |
dc.identifier.citation | The Journal of Immunology, 2006, 176: 451-462 | en_US |
dc.identifier.issn | 0022-1767 | - |
dc.identifier.uri | http://hdl.handle.net/10261/4921 | - |
dc.description | Article available at http://www.jimmunol.org/cgi/content/abstract/176/1/451 | en_US |
dc.description.abstract | African swine fever virus (ASFV) is able to inhibit TNF--induced gene expression through the synthesis of A238L protein. This was shown by the use of deletion mutants lacking the A238L gene from the Vero cell-adapted Ba71V ASFV strain and from the virulent isolate E70. To further analyze the molecular mechanism by which the viral gene controls TNF-, we have used Jurkat cells stably transfected with the viral gene to identify the TNF- regulatory elements involved in the induction of the gene after stimulation with PMA and calcium ionophore. We have thus identified the cAMP-responsive element and 3 sites on the TNF- promoter as the responsible of the gene activation, and demonstrate that A238L inhibits TNF- expression through these DNA binding sites. This inhibition was partially reverted by overexpression of the transcriptional factors NF-AT, NF-B, and c-Jun. Furthermore, we present evidence that A238L inhibits the activation of TNF- by modulating NF-B, NF-AT, and c-Jun trans activation through a mechanism that involves CREB binding protein/p300 function, because overexpression of these transcriptional coactivators recovers TNF- promoter activity. In addition, we show that A238L is a nuclear protein that binds to the cyclic AMP-responsive element/3 complex, thus displacing the CREB binding protein/p300 coactivators. Taken together, these results establish a novel mechanism in the control of TNF- gene expression by a viral protein that could represent an efficient strategy used by ASFV to evade the innate immune response | en_US |
dc.description.sponsorship | This work was supported by grants from Ministerio de Educación y Ciencia (BFU2004-00298/BMC), the Wellcome Trust (075813/C/04/z), and by an institutional grant from the Fundación Ramón Areces. C.H. was a fellow from Fundación Ramón Areces. | en_US |
dc.format.extent | 3436629 bytes | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | en_US |
dc.publisher | American Association of Immunologists | en_US |
dc.rights | openAccess | en_US |
dc.subject | ASFV | en_US |
dc.subject | A238L protein | en_US |
dc.title | The Viral Protein A238L Inhibits TNF-α Expression through a CBP/p300 Transcriptional Coactivators Pathway | en_US |
dc.type | artículo | en_US |
dc.description.peerreviewed | Peer reviewed | en_US |
dc.identifier.e-issn | 1550-6606 | - |
dc.contributor.funder | Ministerio de Educación y Ciencia (España) | - |
dc.contributor.funder | Wellcome Trust | - |
dc.contributor.funder | Fundación Ramón Areces | - |
dc.identifier.funder | http://dx.doi.org/10.13039/100004440 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/100008054 | es_ES |
dc.type.coar | http://purl.org/coar/resource_type/c_6501 | es_ES |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.fulltext | With Fulltext | - |
item.cerifentitytype | Publications | - |
item.openairetype | artículo | - |
item.languageiso639-1 | en | - |
item.grantfulltext | open | - |
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