Article: article from journal or magazin.
IB1/JIP-1 controls JNK activation and increased during prostatic LNCaP cells neuroendocrine differentiation.
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
The scaffold protein Islet-Brain1/c-Jun amino-terminal kinase Interacting Protein-1 (IB1/JIP-1) is a modulator of the c-Jun N-terminal kinase (JNK) activity, which has been implicated in pleiotrophic cellular functions including cell differentiation, division, and death. In this study, we described the presence of IB1/JIP-1 in epithelium of the rat prostate as well as in the human prostatic LNCaP cells. We investigated the functional role of IB1/JIP-1 in LNCaP cells exposed to the proapoptotic agent N-(4-hydroxyphenyl)retinamide (4-HPR) which induced a reduction of IB1/JIP-1 content and a concomittant increase in JNK activity. Conversely, IB1/JIP-1 overexpression using a viral gene transfer prevented the JNK activation and the 4-HPR-induced apoptosis was blunted. In prostatic adenocarcinoma cells, the neuroendocrine (NE) phenotype acquisition is associated with tumor progression and androgen independence. During NE transdifferentiation of LNCaP cells, IB1/JIP-1 levels were increased. This regulated expression of IB1/JIP-1 is secondary to a loss of the neuronal transcriptional repressor neuron restrictive silencing factor (NRSF/REST) function which is known to repress IB1/JIP-1. Together, these results indicated that IB1/JIP-1 participates to the neuronal phenotype of the human LNCaP cells and is a regulator of JNK signaling pathway.
Adaptor Proteins, Signal Transducing, Adenocarcinoma, Adenoviridae, Animals, Apoptosis, Benzimidazoles, Blotting, Northern, Blotting, Western, Cell Differentiation, Cell Line, Tumor, Densitometry, Disease Progression, Enzyme Activation, Epithelial Cells, Fenretinide, Gene Expression Regulation, Neoplastic, Hela Cells, Humans, JNK Mitogen-Activated Protein Kinases, Luciferases, MAP Kinase Kinase 4, Male, Microscopy, Fluorescence, Mitogen-Activated Protein Kinase Kinases, Neoplasms, Neurons, Neurosecretory Systems, Phenotype, Plasmids, Prostate, Prostatic Neoplasms, RNA, Rats, Repressor Proteins, Reverse Transcriptase Polymerase Chain Reaction, Synaptophysin, Tetrazolium Salts, Thiazoles, Tissue Distribution, Transcription Factors, Transcription, Genetic, Up-Regulation
Web of science
Last modification date