IB1/JIP-1 controls JNK activation and increased during prostatic LNCaP cells neuroendocrine differentiation
- 作者：Tawadros ; Thomas ; Martin ; David ; Abderrahmani ; Amar ; Leisinger ; Hans-J脙脙rg ; Waeber ; G脙脙rard ; et. al.
- 关键词：Apoptosis ; Adenovirus ; JNK activity transcriptional repressor protein ; Prostatic cells ; Neuroendocrine differentiation
- 刊名：Cellular Signalling
- 出版年：2005
- 期刊代码：42_08986568
- 类别：bio
- 出版时间：August, 2005
- 卷：17
- 期：8
- 页码：929-939
- 文件大小：478 K
摘要
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.