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dc.contributor.authorLopez-Huertas, Maria Rosa 
dc.contributor.authorLi, Jasmine
dc.contributor.authorZafar, Anjum
dc.contributor.authorRodriguez‑Mora, Sara 
dc.contributor.authorGarcia-Dominguez, Carlota A 
dc.contributor.authorMateos, Elena 
dc.contributor.authorAlcamí, José 
dc.contributor.authorRao, Sudha
dc.contributor.authorCoiras, Mayte 
dc.date.accessioned2018-03-21T07:10:22Z
dc.date.available2018-03-21T07:10:22Z
dc.date.issued2016-02-29
dc.identifier.citationFront Immunol. 2016;7:69.es_ES
dc.identifier.issn1664-3224es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/5770
dc.description.abstractPKCθ is essential for the activation of CD4(+) T cells. Upon TCR/CD28 stimulation, PKCθ is phosphorylated and migrates to the immunological synapse, inducing the activation of cellular transcription factors such as NF-κB and kinases as ERK that are critical for HIV-1 replication. We previously demonstrated that PKCθ is also necessary for HIV-1 replication but the precise mechanism is unknown. Efficient HIV-1 transcription and elongation are absolutely dependent on the synergy between NF-κB and the viral regulator Tat. Tat exerts its function by binding a RNA stem-loop structure proximal to the viral mRNA cap site termed TAR. Besides, due to its effect on cellular metabolic pathways, Tat causes profound changes in infected CD4(+) T cells such as the activation of NF-κB and ERK. We hypothesized that the aberrant upregulation of Tat-mediated activation of NF-κB and ERK occurred through PKCθ signaling. In fact, Jurkat TetOff cells with stable and doxycycline-repressible expression of Tat (Jurkat-Tat) expressed high levels of mRNA for PKCθ. In these cells, PKCθ located at the plasma membrane was phosphorylated at T(538) residue in undivided cells, in the absence of stimulation. Treatment with doxycycline inhibited PKCθ phosphorylation in Jurkat-Tat, suggesting that Tat expression was directly related to the activation of PKCθ. Both NF-κB and Ras/Raf/MEK/ERK signaling pathway were significantly activated in Jurkat-Tat cells, and this correlated with high transactivation of HIV-1 LTR promoter. RNA interference for PKCθ inhibited NF-κB and ERK activity, as well as LTR-mediated transactivation even in the presence of Tat. In addition to Tat-mediated activation of PKCθ in the cytosol, we demonstrated by sequential ChIP that Tat and PKCθ coexisted in the same complex bound at the HIV-1 LTR promoter, specifically at the region containing TAR loop. In conclusion, PKCθ-Tat interaction seemed to be essential for HIV-1 replication in CD4(+) T cells and could be used as a therapeutic target.es_ES
dc.description.sponsorshipThis work was supported by the Spanish Ministry of Economy and Competitiveness (SAF2010-18388, SAF2013-44677-R, FIS PI12/00506); FIPSE (360924/10); the SPANISH AIDS Research Network RD12/0017/0015 that is included in the Spanish I + D + I Plan and is cofinanced by ISCIII-Subdirección General de Evaluacion and European Funding for Regional Development (FEDER); EUROPRISE Network of Excellence of the EU, grant number LSHP CT-2006-037611, and Agence nationale de recherches sur le sida et les hépatites virales (ANRS 2014-2). The work of EM is supported by a contract of the Instituto de Salud Carlos III (Spain) (MPY 1371/12). The work of SR-M is supported by a fellowship of Sara Borrell from Spanish Ministry of Economy and Competitiveness. The work of ML-H is supported by a fellowship of the European Union Programme Health 2009 (CHAARM).es_ES
dc.language.isoenges_ES
dc.publisherFrontiers Mediaes_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectCD4+ T cell activationes_ES
dc.subjectHIV-1 Tat regulatores_ES
dc.subjectNF-kappa Bes_ES
dc.subjectPKC theta and HIV-1 Tat interactiones_ES
dc.subjectPKC theta mRNA interferencees_ES
dc.subjectRas/Raf/MEK/Erk pathwayes_ES
dc.subjectnuclear colocalizationes_ES
dc.subjectprotein kinase C thetaes_ES
dc.titlePKCθ and HIV-1 Transcriptional Regulator Tat Co-exist at the LTR Promoter in CD4+ T Cellses_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID26973648es_ES
dc.format.volume7es_ES
dc.format.page69es_ES
dc.identifier.doi10.3389/fimmu.2016.00069es_ES
dc.contributor.funderMinisterio de Economía y Competitividad (España)
dc.contributor.funderRed de Investigación Cooperativa en Investigación en Sida
dc.contributor.funderInstituto de Salud Carlos III 
dc.contributor.funderUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
dc.contributor.funderAgence Nationale de Recherches sur le sida et les hépatites virales (Francia)
dc.description.peerreviewedes_ES
dc.relation.publisherversionhttps://doi.org/10.3389/fimmu.2016.00069es_ES
dc.identifier.journalFrontiers in Immunologyes_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.repisalud.institucionISCIIIes_ES
dc.relation.projectIDMINECO/ICTI2013-2016/SAF2013-44677-Res_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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