Article: article from journal or magazin.
The scaffold protein IB1/JIP-1 controls the activation of JNK in rat stressed urothelium.
Journal of cell science
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
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.
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
Web of science
Last modification date