Alix and ALG-2 are involved in tumor necrosis factor receptor 1-induced cell death
Autor: | Sakina Torch, Rémy Sadoul, Jérôme Garin, Christine Chatellard-Causse, Béatrice Blot, Anne Petiot, Kimberley Freeman, Flavie Strappazzon, Jean Marc Verna, Sandrine Fraboulet, Loriane Kuhn, Anne-Laure Mahul-Mellier |
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Přispěvatelé: | Fraboulet, Sandrine, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'étude de la dynamique des protéomes (LEDyP), Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Collaboration |
Jazyk: | angličtina |
Rok vydání: | 2008 |
Předmět: |
MESH: Cell Death
MESH: Neurons Cell Cycle Proteins Chick Embryo MESH: Calcium-Binding Proteins Biochemistry MESH: Caspase 8 MESH: Recombinant Proteins MESH: Protein Structure Tertiary 0302 clinical medicine Calcium-binding protein MESH: Animals Caspase Neurons MESH: Receptors Tumor Necrosis Factor Type I Caspase 8 0303 health sciences Cell Death biology MESH: Chick Embryo Endocytosis Recombinant Proteins Cell biology Neural Crest Receptors Tumor Necrosis Factor Type I 030220 oncology & carcinogenesis MESH: Endocytosis Endosome Endosomes ESCRT 03 medical and health sciences Molecular Basis of Cell and Developmental Biology MESH: Cell Cycle Proteins [SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology Animals Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Cell Cycle Protein Molecular Biology 030304 developmental biology Binding Sites MESH: Humans Endosomal Sorting Complexes Required for Transport MESH: Apoptosis Regulatory Proteins Calcium-Binding Proteins Cell Biology MESH: Neural Crest Protein Structure Tertiary MESH: Binding Sites MESH: Endosomes biology.protein Tumor necrosis factor receptor 1 Apoptosis Regulatory Proteins |
Zdroj: | Journal of Biological Chemistry Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2008, 283 (50), pp.34954-65. ⟨10.1074/jbc.M803140200⟩ Journal of Biological Chemistry, 2008, 283 (50), pp.34954-65. ⟨10.1074/jbc.M803140200⟩ |
ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M803140200⟩ |
Popis: | International audience; 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. |
Databáze: | OpenAIRE |
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