dc.contributor.author |
Moubarak, Rana S. |
dc.contributor.author |
Planells Ferrer, Laura |
dc.contributor.author |
Urresti, Jorge |
dc.contributor.author |
Reix, Stéphanie |
dc.contributor.author |
Segura Ginard, Miguel Francisco |
dc.contributor.author |
Carriba, Paulina |
dc.contributor.author |
Marqués Fernàndez, Fernando |
dc.contributor.author |
Solé Serra, Carme |
dc.contributor.author |
Llecha Cano, Núria |
dc.contributor.author |
López Soriano, Joaquin |
dc.contributor.author |
Sanchis, Daniel |
dc.contributor.author |
Yuste Mateos, Víctor J. (Víctor José) |
dc.contributor.author |
Comella i Carnicé, Joan Xavier |
dc.date |
2016-11-14T10:38:32Z |
dc.date |
2013 |
dc.identifier |
0270-6474 |
dc.identifier |
http://hdl.handle.net/10459.1/58487 |
dc.identifier |
https://doi.org/10.1523/JNEUROSCI.2479-13.2013 |
dc.identifier.uri |
http://hdl.handle.net/10459.1/58487 |
dc.description |
The neuronal long isoform of Fas Apoptotic Inhibitory Molecule (FAIM-L) protects from death receptor (DR)-induced apoptosis, yet its mechanism of protection remains unknown. Here, we show that FAIM-L protects rat neuronal Type II cells from Fas-induced apoptosis. XIAP has previously emerged as a molecular discriminator that is upregulated in Type II and downregulated in Type I apoptotic signaling. We demonstrate that FAIM-L requires sustained endogenous levels of XIAP to protect Type II cells as well as murine cortical neurons from Fas-induced apoptosis. FAIM-L interacts with the BIR2 domain of XIAP through an IAP-binding motif, the mutation of which impairs the antiapoptotic function of FAIM-L. Finally, we report that FAIM-L inhibits XIAP auto-ubiquitinylation and maintains its stability, thus conferring protection from apoptosis. Our results bring new understanding of the regulation of endogenous XIAP by a DR antagonist, pointing out at FAIM-L as a promising therapeutic tool for protection from apoptosis in pathological situations where XIAP levels are decreased. |
dc.description |
This work was funded by the Spanish Government Ministerio de Sanidad y Consumo (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, CB06/05/1104 to J.X.C.), Ministerio de Economía y Competitividad (SAF2010–19953 to J.X.C.; SAF2012–31485 to V.J.Y.), Instituto de Salud Carlos III (CP11/00052 to M.F.S.), and the Generalitat de Catalunya (Suport als Grups de Recerca Consolidats 2009SGR346). F.M.-F. and L.P.-F. are supported by postgraduate fellowships from the Spanish Government Ministerio de Educación y Ciencia. J.U. is supported by a postgraduate fellowship from the Generalitat de Catalunya. R.S.M. and V.J.Y. were under the Juan de la Cierva and the Ramon y Cajal programs, respectively, from the Ministerio de Educación y Ciencia (Spain), cofinanced by the European Social Fund. M.F.S. is under the Miguel Servet program from the Instituto de Salud Carlos III and cofinanced by the European Regional Development Fund. |
dc.language |
eng |
dc.publisher |
Society for Neuroscience |
dc.relation |
MICINN/PN2008-2011/SAF2010-19953 |
dc.relation |
MICINN/PN2008-2011/SAF2012-31485 |
dc.relation |
Reproducció del document publicat a https://doi.org/10.1523/JNEUROSCI.2479-13.2013 |
dc.relation |
The Journal of Neuroscience, 2013, vol. 33, núm. 49, p 19262-19275 |
dc.rights |
cc-by (c) Moubarak et al., 2013 |
dc.rights |
http://creativecommons.org/licenses/by/3.0/es/ |
dc.rights |
info:eu-repo/semantics/openAccess |
dc.title |
FAIM-L Is an IAP-Binding Protein That Inhibits XIAP Ubiquitinylation and Protects from Fas-Induced Apoptosis |
dc.type |
article |
dc.type |
publishedVersion |