Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes

Détails

ID Serval
serval:BIB_72500BD485B1
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes
Périodique
Cell
Auteur(s)
Micheau  O., Tschopp  J.
ISSN
0092-8674 (Print)
Statut éditorial
Publié
Date de publication
07/2003
Volume
114
Numéro
2
Pages
181-90
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jul 25
Résumé
Apoptosis induced by TNF-receptor I (TNFR1) is thought to proceed via recruitment of the adaptor FADD and caspase-8 to the receptor complex. TNFR1 signaling is also known to activate the transcription factor NF-kappa B and promote survival. The mechanism by which this decision between cell death and survival is arbitrated is not clear. We report that TNFR1-induced apoptosis involves two sequential signaling complexes. The initial plasma membrane bound complex (complex I) consists of TNFR1, the adaptor TRADD, the kinase RIP1, and TRAF2 and rapidly signals activation of NF-kappa B. In a second step, TRADD and RIP1 associate with FADD and caspase-8, forming a cytoplasmic complex (complex II). When NF-kappa B is activated by complex I, complex II harbors the caspase-8 inhibitor FLIP(L) and the cell survives. Thus, TNFR1-mediated-signal transduction includes a checkpoint, resulting in cell death (via complex II) in instances where the initial signal (via complex I, NF-kappa B) fails to be activated.
Mots-clé
*Adaptor Proteins, Signal Transducing Antigens, CD95/metabolism Apoptosis/*physiology CASP8 and FADD-Like Apoptosis Regulating Protein Carrier Proteins/metabolism Caspase 8 Caspase 9 Caspases/antagonists & inhibitors/metabolism Cell Membrane/metabolism Cell Survival/physiology Cytoplasm/metabolism Fas-Associated Death Domain Protein Humans *Intracellular Signaling Peptides and Proteins Jurkat Cells Models, Biological NF-kappa B/drug effects/genetics/metabolism Nuclear Pore Complex Proteins/metabolism Proteins/genetics/immunology/*metabolism *RNA-Binding Proteins Receptors, Tumor Necrosis Factor/genetics/immunology/*metabolism *Signal Transduction TNF Receptor-Associated Factor 1 Trans-Activation (Genetics) Tumor Cells, Cultured Tumor Necrosis Factor-alpha/metabolism/pharmacology
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 16:18
Dernière modification de la notice
08/05/2019 20:21
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