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

Anne Laure Mahul-Mellier, Flavie Strappazzon, Anne Petiot, Christine Chatellard-Causse, Sakina Torch, Béatrice Blot, Kimberley Freeman, Loriane Kuhn, Jérome Garin, Jean Marc Verna, Sandrine Fraboulet, Rémy Sadoul

Research output: Contribution to journalArticlepeer-review


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 TNFα 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 (AlixΔALG-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 AlixΔALG-2, is regulated by TNF-R1. Taken together, these results highlight Alix and ALG-2 as new actors of the TNF-R1 pathway.

Original languageEnglish
Pages (from-to)34954-34965
Number of pages12
JournalJournal of Biological Chemistry
Issue number50
Publication statusPublished - Dec 12 2008

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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