FAIM-L is an IAP-binding protein that inhibits XIAP ubiquitinylation and protects from fas-induced apoptosis

Rana S. Moubarak, Laura Planells-Ferrer, Jorge Urresti, Stéphanie Reix, Miguel F. Segura, Paulina Carriba, Fernando Marqués-Fernàndez, Carme Sole, Nuria Llecha-Cano, Joaquin Lopez-Soriano, Daniel Sanchis, Victor J. Yuste, Joan X. Comella

Research output: Contribution to journalArticleResearchpeer-review

13 Citations (Scopus)

Abstract

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. XIAPhas 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. © 2013 the authors.
Original languageEnglish
Pages (from-to)19262-19275
JournalJournal of Neuroscience
Volume33
Issue number49
DOIs
Publication statusPublished - 9 Dec 2013

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