IB1/JIP-1 Controls JNK Activation and Increased During Prostatic LNCaP Cells Neuroendocrine Differentiation

Cell Signal. 2005 Aug;17(8):929-39. doi: 10.1016/j.cellsig.2004.11.013. Epub 2005 Mar 3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / physiology*
  • Adenocarcinoma / metabolism
  • Adenoviridae / genetics
  • Animals
  • Apoptosis
  • Benzimidazoles / pharmacology
  • Blotting, Northern
  • Blotting, Western
  • Cell Differentiation
  • Cell Line, Tumor
  • Densitometry
  • Disease Progression
  • Enzyme Activation
  • Epithelial Cells / metabolism
  • Fenretinide / pharmacology
  • Gene Expression Regulation, Neoplastic*
  • HeLa Cells
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Luciferases / metabolism
  • MAP Kinase Kinase 4
  • Male
  • Microscopy, Fluorescence
  • Mitogen-Activated Protein Kinase Kinases / metabolism*
  • Neoplasms / pathology
  • Neurons / metabolism
  • Neurosecretory Systems / metabolism*
  • Phenotype
  • Plasmids / metabolism
  • Prostate / metabolism
  • Prostatic Neoplasms / pathology*
  • RNA / metabolism
  • Rats
  • Repressor Proteins / physiology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Synaptophysin / metabolism
  • Tetrazolium Salts / pharmacology
  • Thiazoles / pharmacology
  • Tissue Distribution
  • Transcription Factors / physiology
  • Transcription, Genetic
  • Up-Regulation

Substances

  • Adaptor Proteins, Signal Transducing
  • Benzimidazoles
  • MAPK8IP1 protein, human
  • RE1-silencing transcription factor
  • Repressor Proteins
  • Synaptophysin
  • Tetrazolium Salts
  • Thiazoles
  • Transcription Factors
  • Fenretinide
  • RNA
  • Luciferases
  • JNK Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • Mitogen-Activated Protein Kinase Kinases
  • thiazolyl blue
  • bisbenzimide ethoxide trihydrochloride