title: IB1/JIP-1 controls JNK activation and increased during prostatic LNCaP cells neuroendocrine differentiation.
abstract: 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.
authors.affiliation: Service of Urology, University Hospital, Lausanne, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Tawadros
authors.forename: David
authors.initials: D
authors.lastname: Martin
authors.forename: Amar
authors.initials: A
authors.lastname: Abderrahmani
authors.forename: Hans-Jürg
authors.initials: HJ
authors.lastname: Leisinger
authors.forename: Gérard
authors.initials: G
authors.lastname: Waeber
authors.forename: Jacques-Antoine
authors.initials: JA
authors.lastname: Haefliger
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000230:Adenocarcinoma / Q000378:metabolism; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D001562:Benzimidazoles / Q000494:pharmacology; D015152:Blotting, Northern; D015153:Blotting, Western; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D003720:Densitometry; D018450:Disease Progression; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000378:metabolism; D017313:Fenretinide / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008156:Luciferases / Q000378:metabolism; D048670:MAP Kinase Kinase 4; D008297:Male; D008856:Microscopy, Fluorescence; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D009369:Neoplasms / Q000473:pathology; D009474:Neurons / Q000378:metabolism; D009490:Neurosecretory Systems / Q000378:metabolism*; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism; D011467:Prostate / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000473:pathology*; D012313:RNA / Q000378:metabolism; D051381:Rats; D012097:Repressor Proteins / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016708:Synaptophysin / Q000378:metabolism; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D014018:Tissue Distribution; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic; D015854:Up-Regulation; D000099229:RE1-Silencing Transcription Factor
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D001562:Benzimidazoles; D017313:Fenretinide; D048031:JNK Mitogen-Activated Protein Kinases; D008156:Luciferases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D012313:RNA; D012097:Repressor Proteins; D016708:Synaptophysin; D013778:Tetrazolium Salts; D013844:Thiazoles; D014157:Transcription Factors; D000099229:RE1-Silencing Transcription Factor; C490666:MAPK8IP1 protein, human; C022616:thiazolyl blue; C017807:bisbenzimide ethoxide trihydrochloride