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Alix and ALG-2 are involved in tumor necrosis factor receptor 1-induced cell death.

Abstract : Alix/AIP1 regulates cell death in a way involving interactions with the calcium-binding protein ALG-2 and with proteins of ESCRT (endosomal sorting complex required for transport). Using mass spectrometry we identified caspase-8 among proteins co-immunoprecipitating with Alix in dying neurons. We next demonstrated that Alix and ALG-2 interact with pro-caspase-8 and that Alix forms a complex with the TNFalpha receptor-1 (TNF-R1), depending on its capacity to bind ESCRT proteins. Thus, Alix and ALG-2 may allow the recruitment of pro-caspase-8 onto endosomes containing TNF-R1, a step thought to be necessary for activation of the apical caspase. In line with this, expression of Alix deleted of its ALG-2-binding site (AlixDeltaALG-2) significantly reduced TNF-R1-induced cell death, without affecting endocytosis of the receptor. In a more physiological setting, we found that programmed cell death of motoneurons, which can be inhibited by AlixDeltaALG-2, is regulated by TNF-R1. Taken together, these results highlight Alix and ALG-2 as new actors of the TNF-R1 pathway.
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Submitted on : Friday, March 26, 2010 - 9:05:54 AM
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Anne-Laure Mahul-Mellier, Flavie Strappazzon, Anne Petiot, Christine Chatellard-Causse, Sakina Torch, et al.. Alix and ALG-2 are involved in tumor necrosis factor receptor 1-induced cell death.. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2008, 283 (50), pp.34954-65. ⟨10.1074/jbc.M803140200⟩. ⟨inserm-00381799⟩

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