The caspase-8 inhibitor FLIP promotes activation of NF-kappaB and Erk signaling pathways.

Détails

ID Serval
serval:BIB_F3D9BDE62A23
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
The caspase-8 inhibitor FLIP promotes activation of NF-kappaB and Erk signaling pathways.
Périodique
Current Biology
Auteur⸱e⸱s
Kataoka T., Budd R.C., Holler N., Thome M., Martinon F., Irmler M., Burns K., Hahne M., Kennedy N., Kovacsovics M., Tschopp J.
ISSN
0960-9822[print], 0960-9822[linking]
Statut éditorial
Publié
Date de publication
2000
Volume
10
Numéro
11
Pages
640-648
Langue
anglais
Résumé
BACKGROUND: Activation of Fas (CD95) by its ligand (FasL) rapidly induces cell death through recruitment and activation of caspase-8 via the adaptor protein Fas-associated death domain protein (FADD). However, Fas signals do not always result in apoptosis but can also trigger a pathway that leads to proliferation. We investigated the level at which the two conflicting Fas signals diverge and the protein(s) that are implicated in switching the response. RESULTS: Under conditions in which proliferation of CD3-activated human T lymphocytes is increased by recombinant FasL, there was activation of the transcription factors NF-kappaB and AP-1 and recruitment of the caspase-8 inhibitor and FADD-interacting protein FLIP (FLICE-like inhibitory protein). Fas-recruited FLIP interacts with TNF-receptor associated factors 1 and 2, as well as with the kinases RIP and Raf-1, resulting in the activation of the NF-kappaB and extracellular signal regulated kinase (Erk) signaling pathways. In T cells these two signal pathways are critical for interleukin-2 production. Increased expression of FLIP in T cells resulted in increased production of interleukin-2. CONCLUSIONS: We provide evidence that FLIP is not simply an inhibitor of death-receptor-induced apoptosis but that it also mediates the activation of NF-kappaB and Erk by virtue of its capacity to recruit adaptor proteins involved in these signaling pathways.
Mots-clé
Antigens, CD3/physiology, Antigens, CD95/physiology, Apoptosis, CASP8 and FADD-Like Apoptosis Regulating Protein, Carrier Proteins/metabolism, Caspase 8, Caspase 9, Caspases/antagonists &amp, inhibitors, Cells, Cultured, Fas Ligand Protein, Humans, Interleukin-2/biosynthesis, Intracellular Signaling Peptides and Proteins, Membrane Glycoproteins/pharmacology, Mitogen-Activated Protein Kinases/metabolism, NF-kappa B/metabolism, Proteins/metabolism, Proto-Oncogene Proteins c-raf, Receptor-Interacting Protein Serine-Threonine Kinases, Receptors, Tumor Necrosis Factor/physiology, Signal Transduction/drug effects, Signal Transduction/physiology, T-Lymphocytes/drug effects, T-Lymphocytes/immunology, TNF Receptor-Associated Factor 1, TNF Receptor-Associated Factor 2, Transcription Factor AP-1/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 15:18
Dernière modification de la notice
20/08/2019 16:20
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