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Título:
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FAIM-L Is an IAP-Binding Protein That Inhibits XIAP Ubiquitinylation and Protects from Fas-Induced Apoptosis
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Autor/a:
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Moubarak, Rana S.; Planells Ferrer, Laura; Urresti, Jorge; Reix, Stéphanie; Segura Ginard, Miguel Francisco; Carriba, Paulina; Marqués Fernàndez, Fernando; Solé Serra, Carme; Llecha Cano, Núria; López Soriano, Joaquin; Sanchis, Daniel; Yuste Mateos, Víctor J. (Víctor José); Comella i Carnicé, Joan Xavier
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Notas:
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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.
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. |
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Derechos:
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cc-by (c) Moubarak et al., 2013
http://creativecommons.org/licenses/by/3.0/es/
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Tipo de documento:
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article
publishedVersion |
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Editor:
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Society for Neuroscience
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