The scaffold protein IB1/JIP-1 controls the activation of JNK in rat stressed urothelium.

Détails

ID Serval
serval:BIB_5E7E586F7BC8
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
The scaffold protein IB1/JIP-1 controls the activation of JNK in rat stressed urothelium.
Périodique
Journal of cell science
Auteur(s)
Tawadros T., Formenton A., Dudler J., Thompson N., Nicod P., Leisinger H.J., Waeber G., Haefliger J.A.
ISSN
0021-9533
Statut éditorial
Publié
Date de publication
2002
Peer-reviewed
Oui
Volume
115
Numéro
Pt 2
Pages
385-93
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Résumé
The c-Jun N-terminal kinase (JNK) is critical for cell survival, differentiation, apoptosis and tumorigenesis. This signalling pathway requires the presence of the scaffold protein Islet-Brain1/c-Jun N-terminal kinase interacting protein-1 (IB1/JIP-1). Immunolabeling and in situ hybridisation of bladder sections showed that IB1/JIP-1 is expressed in urothelial cells. The functional role of IB1/JIP-1 in the urothelium was therefore studied in vivo in a model of complete rat bladder outlet obstruction. This parietal stress, which is due to urine retention, reduced the content of IB1/JIP-1 in urothelial cells and consequently induced a drastic increase in JNK activity and AP-1 binding activity. Using a viral gene transfer approach, the stress-induced activation of JNK was prevented by overexpressing IB1/JIP-1. Conversely, the JNK activity was increased in urothelial cells where the IB1/JIP-1 content was experimentally reduced using an antisense RNA strategy. Furthermore, JNK activation was found to be increased in non-stressed urothelial cells of heterozygous mice carrying a selective disruption of the IB1/JIP-1 gene. These data established that mechanical stress in urothelial cells in vivo induces a robust JNK activation as a consequence of regulated expression of the scaffold protein IB1/JIP-1. This result highlights a critical role for that scaffold protein in the homeostasis of the urothelium and unravels a new potential target to regulate the JNK pathway in this tissue.
Mots-clé
Adaptor Proteins, Signal Transducing, Animals, Carrier Proteins, Down-Regulation, Genetic Vectors, JNK Mitogen-Activated Protein Kinases, MAP Kinase Signaling System, Male, Mitogen-Activated Protein Kinases, Nuclear Proteins, Phosphorylation, Proto-Oncogene Proteins c-jun, Rats, Rats, Wistar, Stress, Physiological, Trans-Activators, Transcription Factor AP-1, Up-Regulation, Urinary Bladder, Urinary Bladder Neoplasms, Urothelium
Pubmed
Web of science
Création de la notice
25/01/2008 14:48
Dernière modification de la notice
20/08/2019 15:16
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