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dc.contributor.author | Coiras, Mayte | |
dc.contributor.author | Lopez-Huertas, Maria Rosa | |
dc.contributor.author | Mateos, Elena | |
dc.contributor.author | Alcamí, José | |
dc.date.accessioned | 2019-03-27T12:47:22Z | |
dc.date.available | 2019-03-27T12:47:22Z | |
dc.date.issued | 2008-12-01 | |
dc.identifier.citation | Retrovirology. 2008 Dec 1;5:109. | es_ES |
dc.identifier.issn | 1742-4690 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/7409 | |
dc.description.abstract | BACKGROUND: 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.sponsorship | This 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.iso | eng | es_ES |
dc.publisher | BioMed Central (BMC) | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject.mesh | Caspase 3 | es_ES |
dc.subject.mesh | Cells, Cultured | es_ES |
dc.subject.mesh | Dimerization | es_ES |
dc.subject.mesh | HIV-1 | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | I-kappa B Proteins | es_ES |
dc.subject.mesh | NF-KappaB Inhibitor alpha | es_ES |
dc.subject.mesh | Protein Binding | es_ES |
dc.subject.mesh | T-Lymphocytes | es_ES |
dc.subject.mesh | Transcription Factor RelA | es_ES |
dc.title | Caspase-3-mediated cleavage of p65/RelA results in a carboxy-terminal fragment that inhibits IkappaBalpha and enhances HIV-1 replication in human T lymphocytes | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 19046417 | es_ES |
dc.format.volume | 5 | es_ES |
dc.format.number | 1 | es_ES |
dc.format.page | 109 | es_ES |
dc.identifier.doi | 10.1186/1742-4690-5-109 | es_ES |
dc.contributor.funder | Instituto de Salud Carlos III | |
dc.contributor.funder | Fundación para la Innovación y la Prospectiva en Salud en España | |
dc.contributor.funder | Comunidad de Madrid (España) | |
dc.description.peerreviewed | Sí | es_ES |
dc.relation.publisherversion | https://doi.org/10.1186/1742-4690-5-109 | es_ES |
dc.identifier.journal | Retrovirology | es_ES |
dc.repisalud.centro | ISCIII::Centro Nacional de Microbiología | es_ES |
dc.repisalud.institucion | ISCIII | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/RD06/0006 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/PI040614 | es_ES |
dc.rights.accessRights | open access | es_ES |