A238L Inhibits NF-ATc2, NF-B, and c-Jun Activation through a Novel Mechanism Involving Protein Kinase C--Mediated Up-Regulation of the Amino-Terminal Transactivation Domain of p300

Article available at http://www.jimmunol.org/cgi/content/abstract/180/4/2429

Detalhes bibliográficos
Autores: Granja, Aitor G., Perkins, Neil D., Revilla Novella, Yolanda
Formato: artículo
Fecha de publicación:2008
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/4922
Acesso em linha:http://hdl.handle.net/10261/4922
Access Level:acceso abierto
Palavra-chave:PKC, protein kinase C
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spelling A238L Inhibits NF-ATc2, NF-B, and c-Jun Activation through a Novel Mechanism Involving Protein Kinase C--Mediated Up-Regulation of the Amino-Terminal Transactivation Domain of p300Granja, Aitor G.Perkins, Neil D.Revilla Novella, YolandaPKC, protein kinase CArticle available at http://www.jimmunol.org/cgi/content/abstract/180/4/2429The transcriptional coactivators CREB-binding protein and p300 regulate inducible transcription in multiple cellular processes and during the establishment of inflammatory and immune response. Several viruses have been shown to interfere with CREB-binding protein/p300 function, modulating their transcriptional activity. In this study, we report that the viral protein A238L interacts with the amino-terminal region of p300, inhibiting the acetylation and transcriptional activation of NF-ATc2, NF-B, and c-Jun in stimulated human T cells. We demonstrate that A238L modulates the autoacetylation of p300 without altering its intrinsic histone acetyl transferase activity. Furthermore, we show that the molecular mechanism of the inhibition executed by the viral protein is conducted through blocking protein kinase C (PKC)-p300 interaction and further acetylation in the amino-terminal transactivation domain of the coactivator, and that Ser384, within the CH1 domain, is essential for the full transcriptional activation of the coactivator. Moreover, we show that overexpression of an active form of PKC- reverts the A238L-mediated inhibition of the transcriptional activity of p300, showing, for the first time, a PKC--mediated up-regulation of the coactivator. These findings provide new strategies to develop therapies potentially useful in the control of disorders related to p300 deregulationThis work was supported by grants from Ministerio de Educación y Ciencia (BFU2004-00298/BMC) and by an institutional grant from the Fundación Ramón Areces. A.G.G. was funded by Centro de Investigación en Sanidad AnimalPeer reviewedAmerican Association of ImmunologistsMinisterio de Educación y Ciencia (España)Fundación Ramón ArecesCentro de Investigación en Sanidad Animal (España)200820082008info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_65011240808 bytesapplication/pdfhttp://hdl.handle.net/10261/4922reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglésinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/49222026-05-22T06:33:51Z
dc.title.none.fl_str_mv A238L Inhibits NF-ATc2, NF-B, and c-Jun Activation through a Novel Mechanism Involving Protein Kinase C--Mediated Up-Regulation of the Amino-Terminal Transactivation Domain of p300
title A238L Inhibits NF-ATc2, NF-B, and c-Jun Activation through a Novel Mechanism Involving Protein Kinase C--Mediated Up-Regulation of the Amino-Terminal Transactivation Domain of p300
spellingShingle A238L Inhibits NF-ATc2, NF-B, and c-Jun Activation through a Novel Mechanism Involving Protein Kinase C--Mediated Up-Regulation of the Amino-Terminal Transactivation Domain of p300
Granja, Aitor G.
PKC, protein kinase C
title_short A238L Inhibits NF-ATc2, NF-B, and c-Jun Activation through a Novel Mechanism Involving Protein Kinase C--Mediated Up-Regulation of the Amino-Terminal Transactivation Domain of p300
title_full A238L Inhibits NF-ATc2, NF-B, and c-Jun Activation through a Novel Mechanism Involving Protein Kinase C--Mediated Up-Regulation of the Amino-Terminal Transactivation Domain of p300
title_fullStr A238L Inhibits NF-ATc2, NF-B, and c-Jun Activation through a Novel Mechanism Involving Protein Kinase C--Mediated Up-Regulation of the Amino-Terminal Transactivation Domain of p300
title_full_unstemmed A238L Inhibits NF-ATc2, NF-B, and c-Jun Activation through a Novel Mechanism Involving Protein Kinase C--Mediated Up-Regulation of the Amino-Terminal Transactivation Domain of p300
title_sort A238L Inhibits NF-ATc2, NF-B, and c-Jun Activation through a Novel Mechanism Involving Protein Kinase C--Mediated Up-Regulation of the Amino-Terminal Transactivation Domain of p300
dc.creator.none.fl_str_mv Granja, Aitor G.
Perkins, Neil D.
Revilla Novella, Yolanda
author Granja, Aitor G.
author_facet Granja, Aitor G.
Perkins, Neil D.
Revilla Novella, Yolanda
author_role author
author2 Perkins, Neil D.
Revilla Novella, Yolanda
author2_role author
author
dc.contributor.none.fl_str_mv Ministerio de Educación y Ciencia (España)
Fundación Ramón Areces
Centro de Investigación en Sanidad Animal (España)
dc.subject.none.fl_str_mv PKC, protein kinase C
topic PKC, protein kinase C
description Article available at http://www.jimmunol.org/cgi/content/abstract/180/4/2429
publishDate 2008
dc.date.none.fl_str_mv 2008
2008
2008
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/4922
url http://hdl.handle.net/10261/4922
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 1240808 bytes
application/pdf
dc.publisher.none.fl_str_mv American Association of Immunologists
publisher.none.fl_str_mv American Association of Immunologists
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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