The scaffold protein IB1/JIP-1 is a critical mediator of cytokine-induced apoptosis in pancreatic beta cells.

Détails

ID Serval
serval:BIB_42B18BB6B855
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
The scaffold protein IB1/JIP-1 is a critical mediator of cytokine-induced apoptosis in pancreatic beta cells.
Périodique
Journal of Cell Science
Auteur(s)
Haefliger J.A., Tawadros T., Meylan L., Gurun S.L., Roehrich M.E., Martin D., Thorens B., Waeber G.
ISSN
0021-9533[print], 0021-9533[linking]
Statut éditorial
Publié
Date de publication
2003
Volume
116
Numéro
Pt 8
Pages
1463-1469
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
In insulin-secreting cells, cytokines activate the c-Jun N-terminal kinase (JNK), which contributes to a cell signaling towards apoptosis. The JNK activation requires the presence of the murine scaffold protein JNK-interacting protein 1 (JIP-1) or human Islet-brain 1(IB1), which organizes MLK3, MKK7 and JNK for proper signaling specificity. Here, we used adenovirus-mediated gene transfer to modulate IB1/JIP-1 cellular content in order to investigate the contribution of IB1/JIP-1 to beta-cell survival. Exposure of the insulin-producing cell line INS-1 or isolated rat pancreatic islets to cytokines (interferon-gamma, tumor necrosis factor-alpha and interleukin-1beta) induced a marked reduction of IB1/JIP-1 content and a concomitant increase in JNK activity and apoptosis rate. This JNK-induced pro-apoptotic program was prevented in INS-1 cells by overproducing IB1/JIP-1 and this effect was associated with inhibition of caspase-3 cleavage. Conversely, reducing IB1/JIP-1 content in INS-1 cells and isolated pancreatic islets induced a robust increase in basal and cytokine-stimulated apoptosis. In heterozygous mice carrying a selective disruption of the IB1/JIP-1 gene, the reduction in IB1/JIP-1 content in happloinsufficient isolated pancreatic islets was associated with an increased JNK activity and basal apoptosis. These data demonstrate that modulation of the IB1-JIP-1 content in beta cells is a crucial regulator of JNK signaling pathway and of cytokine-induced apoptosis.
Mots-clé
Adaptor Proteins, Signal Transducing, Animals, Apoptosis/drug effects, Blotting, Western, Carrier Proteins/genetics, Carrier Proteins/metabolism, Cell Line, Cells, Cultured, Cytokines/pharmacology, DNA Fragmentation/drug effects, Genotype, Interferon-gamma/pharmacology, Interleukin-1/pharmacology, Islets of Langerhans/cytology, Islets of Langerhans/drug effects, JNK Mitogen-Activated Protein Kinases, Male, Mice, Mitogen-Activated Protein Kinases/drug effects, Mitogen-Activated Protein Kinases/metabolism, Nuclear Proteins/genetics, Nuclear Proteins/metabolism, Rats, Rats, Wistar, Trans-Activators/genetics, Trans-Activators/metabolism, Transfection, Tumor Necrosis Factor-alpha/pharmacology
Pubmed
Web of science
Création de la notice
17/11/2008 9:57
Dernière modification de la notice
20/08/2019 14:45
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