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dc.contributor.authorCoiras, Mayte 
dc.contributor.authorLopez-Huertas, Maria Rosa 
dc.contributor.authorMateos, Elena 
dc.contributor.authorAlcamí, José 
dc.date.accessioned2019-03-27T12:47:22Z
dc.date.available2019-03-27T12:47:22Z
dc.date.issued2008-12-01
dc.identifier.citationRetrovirology. 2008 Dec 1;5:109.es_ES
dc.identifier.issn1742-4690es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/7409
dc.description.abstractBACKGROUND: Degradation of p65/RelA has been involved in both the inhibition of NF-kappaB-dependent activity and the onset of apoptosis. However, the mechanisms of NF-kappaB degradation are unclear and can vary depending on the cell type. Cleavage of p65/RelA can produce an amino-terminal fragment that was shown to act as a dominant-negative inhibitor of NF-kappaB, thereby promoting apoptosis. However, the opposite situation has also been described and the production of a carboxy-terminal fragment that contains two potent transactivation domains has also been related to the onset of apoptosis. In this context, a carboxy-terminal fragment of p65/RelA (DeltaNH2p65), detected in non-apoptotic human T lymphocytes upon activation, has been studied. T cells constitute one of the long-lived cellular reservoirs of the human immunodeficiency virus type 1 (HIV-1). Because NF-kappaB is the most important inducible element involved in initiation of HIV-1 transcription, an adequate control of NF-kappaB response is of paramount importance for both T cell survival and viral spread. Its major inhibitor IkappaBalpha constitutes a master terminator of NF-kappaB response that is complemented by degradation of p65/RelA. RESULTS AND CONCLUSIONS: In this study, the function of a caspase-3-mediated carboxy-terminal fragment of p65/RelA, which was detected in activated human peripheral blood lymphocytes (PBLs), was analyzed. Cells producing this truncated p65/RelA did not undergo apoptosis but showed a high viability, in spite of caspase-3 activation. DeltaNH2p65 lacked most of DNA-binding domain but retained the dimerization domain, NLS and transactivation domains. Consequently, it could translocate to the nucleus, associate with NF-kappaB1/p50 and IkappaBalpha, but could not bind -kappaB consensus sites. However, although DeltaNH2p65 lacked transcriptional activity by itself, it could increase NF-kappaB activity in a dose-dependent manner by hijacking IkappaBalpha. Thus, its expression resulted in a persistent transactivation activity of wild-type p65/RelA, as well as an improvement of HIV-1 replication in PBLs. Moreover, DeltaNH2p65 was increased in the nuclei of PMA-, PHA-, and TNFalpha-activated T cells, proving this phenomenon was related to cell activation. These data suggest the existence of a novel mechanism for maintaining NF-kappaB activity in human T cells through the binding of the carboxy-terminal fragment of p65/RelA to IkappaBalpha in order to protect wild-type p65/RelA from IkappaBalpha inhibition.es_ES
dc.description.sponsorshipThis work was supported by the following projects: FIPSE 36633/07; ISCIII-RETIC RD06/0006; FIPSE 36584/06; FIS PI040614; Network of Excellence EUROPRISE; and VIRHOST Network from Comunidad de Madrid, Spain. M.R. López-Huertas is a pre-doctoral fellow funded by FIPSE 36453/03 and "Plan Nacional del SIDA" (MVI 1434/05-5).es_ES
dc.language.isoenges_ES
dc.publisherBiomed Centrales_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subject.meshCaspase 3 es_ES
dc.subject.meshCells, Cultured es_ES
dc.subject.meshDimerization es_ES
dc.subject.meshHIV-1 es_ES
dc.subject.meshHumans es_ES
dc.subject.meshI-kappa B Proteins es_ES
dc.subject.meshNF-KappaB Inhibitor alpha es_ES
dc.subject.meshProtein Binding es_ES
dc.subject.meshT-Lymphocytes es_ES
dc.subject.meshTranscription Factor RelA es_ES
dc.titleCaspase-3-mediated cleavage of p65/RelA results in a carboxy-terminal fragment that inhibits IkappaBalpha and enhances HIV-1 replication in human T lymphocyteses_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID19046417es_ES
dc.format.volume5es_ES
dc.format.number1es_ES
dc.format.page109es_ES
dc.identifier.doi10.1186/1742-4690-5-109es_ES
dc.contributor.funderInstituto de Salud Carlos III - ISCIII
dc.contributor.funderFundación para la Innovación y la Prospectiva en Salud en España (FIPSE)
dc.contributor.funderGobierno de la Comunidad Autónoma de Madrid
dc.description.peerreviewedes_ES
dc.relation.publisherversionhttps://doi.org/10.1186/1742-4690-5-109es_ES
dc.identifier.journalRetrovirologyes_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.repisalud.institucionISCIIIes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/RD06/0006es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI040614es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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