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 journalArticle

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 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
Volume283
Issue number50
DOIs
Publication statusPublished - Dec 12 2008

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Tumor Necrosis Factor Receptors
Cell death
Cell Death
Caspase 8
Endosomal Sorting Complexes Required for Transport
Binding Sites
Calcium-Binding Proteins
Endosomes
Motor Neurons
Protein Transport
Caspases
Endocytosis
Neurons
Mass spectrometry
Mass Spectrometry
Carrier Proteins
Proteins
Chemical activation

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Mahul-Mellier, A. L., Strappazzon, F., Petiot, A., Chatellard-Causse, C., Torch, S., Blot, B., ... Sadoul, R. (2008). Alix and ALG-2 are involved in tumor necrosis factor receptor 1-induced cell death. Journal of Biological Chemistry, 283(50), 34954-34965. https://doi.org/10.1074/jbc.M803140200

Alix and ALG-2 are involved in tumor necrosis factor receptor 1-induced cell death. / Mahul-Mellier, Anne Laure; Strappazzon, Flavie; Petiot, Anne; Chatellard-Causse, Christine; Torch, Sakina; Blot, Béatrice; Freeman, Kimberley; Kuhn, Loriane; Garin, Jérome; Verna, Jean Marc; Fraboulet, Sandrine; Sadoul, Rémy.

In: Journal of Biological Chemistry, Vol. 283, No. 50, 12.12.2008, p. 34954-34965.

Research output: Contribution to journalArticle

Mahul-Mellier, AL, Strappazzon, F, Petiot, A, Chatellard-Causse, C, Torch, S, Blot, B, Freeman, K, Kuhn, L, Garin, J, Verna, JM, Fraboulet, S & Sadoul, R 2008, 'Alix and ALG-2 are involved in tumor necrosis factor receptor 1-induced cell death', Journal of Biological Chemistry, vol. 283, no. 50, pp. 34954-34965. https://doi.org/10.1074/jbc.M803140200
Mahul-Mellier, Anne Laure ; Strappazzon, Flavie ; Petiot, Anne ; Chatellard-Causse, Christine ; Torch, Sakina ; Blot, Béatrice ; Freeman, Kimberley ; Kuhn, Loriane ; Garin, Jérome ; Verna, Jean Marc ; Fraboulet, Sandrine ; Sadoul, Rémy. / Alix and ALG-2 are involved in tumor necrosis factor receptor 1-induced cell death. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 50. pp. 34954-34965.
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