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Author | dc.contributor.author | Groenendyk, Jody | |
Author | dc.contributor.author | Paskevicius, Tautvydas | |
Author | dc.contributor.author | Urra, Hery | |
Author | dc.contributor.author | Viricel, Clement | |
Author | dc.contributor.author | Wang, Kui | |
Author | dc.contributor.author | Barakat, Khaled | |
Author | dc.contributor.author | Hetz Flores, Claudio | |
Author | dc.contributor.author | Kurgan, Lukasz | |
Author | dc.contributor.author | Agellon, Luis B. | |
Author | dc.contributor.author | Michalak, Marek | |
Admission date | dc.date.accessioned | 2019-03-18T12:03:55Z | |
Available date | dc.date.available | 2019-03-18T12:03:55Z | |
Publication date | dc.date.issued | 2018 | |
Cita de ítem | dc.identifier.citation | Scientific Reports, Volumen 8, Issue 1, 2018, | |
Identifier | dc.identifier.issn | 20452322 | |
Identifier | dc.identifier.other | 10.1038/s41598-018-34891-w | |
Identifier | dc.identifier.uri | https://repositorio.uchile.cl/handle/2250/167712 | |
Abstract | dc.description.abstract | © 2018, The Author(s). Cyclosporine, a widely used immunosuppressant in organ transplantation and in treatment of various autoimmune diseases, activates the unfolded protein response (UPR), an ER stress coping response. In this study we discovered a new and unanticipated cyclosporine-dependent signaling pathway, with cyclosporine triggering direct activation of the UPR. COX-2 binds to and activates IRE1α, leading to IRE1α splicing of XBP1 mRNA. Molecular interaction and modeling analyses identified a novel interaction site for cyclosporine with COX-2 which caused enhancement of COX-2 enzymatic activity required for activation of the IRE1α branch of the UPR. Cyclosporine-dependent activation of COX-2 and IRE1α in mice indicated that cyclosporine-COX-2-IRE1α signaling pathway was functional in vivo. These findings identify COX-2 as a new IRE1α binding partner and regulator of the IRE1α branch of the UPR pathway, and establishes the mechanism underlying cytotoxicity associated with chroni | |
Lenguage | dc.language.iso | en | |
Publisher | dc.publisher | Nature Publishing Group | |
Type of license | dc.rights | Attribution-NonCommercial-NoDerivs 3.0 Chile | |
Link to License | dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/cl/ | |
Source | dc.source | Scientific Reports | |
Keywords | dc.subject | Multidisciplinary | |
Título | dc.title | Cyclosporine A binding to COX-2 reveals a novel signaling pathway that activates the IRE1α unfolded protein response sensor | |
Document type | dc.type | Artículo de revista | |
dcterms.accessRights | dcterms.accessRights | Acceso Abierto | |
Cataloguer | uchile.catalogador | SCOPUS | |
Indexation | uchile.index | Artículo de publicación SCOPUS | |
uchile.cosecha | uchile.cosecha | SI | |
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