FAIM-L is an IAP-binding protein that inhibits XIAP ubiquitinylation and protects from Fas-induced apoptosis.
J Neurosci
; 33(49): 19262-75, 2013 Dec 04.
Article
em En
| MEDLINE
| ID: mdl-24305822
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. 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.
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Base de dados:
MEDLINE
Assunto principal:
Apoptose
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Fármacos Neuroprotetores
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Receptor fas
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Proteínas Reguladoras de Apoptose
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Proteínas Inibidoras de Apoptose
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Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X
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Ubiquitinação
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article