p23 co-chaperone protects the aryl hydrocarbon receptor from degradation in mouse and human cell lines.
p23 co-chaperone protects the aryl hydrocarbon receptor from degradation in mouse and human cell lines.
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DOI：
10.1016/j.bcp.2012.06.018
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发表时间：
2012-09-15
影响因子：
5.8
通讯作者：
Chan, William K.
中科院分区：
文献类型：
--
作者：
Phuong Minh Nguyen;Wang, Depeng;Wang, Yu;Li, Yanjie;Uchizono, James A.;Chan, William K.
芳烃受体（aryl hydrocarbon receptor，AhR）是一种配体敏感的转录因子，与大多数2，3，7，8-四氯二苯并-p-二恶英毒性有关。在没有配体的情况下，AhR复合物是细胞质的并且含有p23。我们的目的是研究野生型p23水平是否对AhR功能很重要。我们通过电穿孔或慢病毒感染产生了8个p23特异性敲低的稳定细胞系。这些稳定的细胞系中有5个是从小鼠肝癌细胞系（Hepa1c1c7）中产生的，3个是从人肝癌和宫颈癌细胞系（Hep3B和HeLa）中产生的。所有这些都表达较低的AhR蛋白水平，导致配体诱导的DRE驱动的下游活性降低。在p23特异性敲低的稳定细胞中的AhR蛋白水平在引入外源性p23后逆转回到野生型水平。这些稳定细胞中AhR蛋白水平的降低是由AhR信息水平的降低和在配体不存在下AhR蛋白降解的增加引起的。AhR的这种配体非依赖性降解对MG132不敏感，表明26S蛋白酶体不负责降解。此外，MG132不能保护AhR免受小鼠和人p23敲低稳定细胞中配体诱导的降解。
The aryl hydrocarbon receptor (AhR) is a ligand-sensitive transcription factor which is responsible for most 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicities. Without ligand, the AhR complex is cytoplasmic and contains p23. Our objective was to investigate whether the wild type p23 levels are important for the AhR function. We generated eight p23-specific knockdown stable cell lines via either electroporation or lentiviral infection. Five of these stable cell lines were generated from a mouse hepatoma cell line (Hepa1c1c7) and three were from human hepatoma and cervical cell lines (Hep3B and HeLa). All of them expressed lower AhR protein levels, leading to reduced ligand-induced, DRE-driven downstream activity. The AhR protein levels in p23-specific knockdown stable cells were reversed back to wild type levels after exogenous p23 was introduced. Reduction of the AhR protein levels in these stable cells was caused by a decrease in the AhR message levels and an increase of the AhR protein degradation in the absence of ligand. This ligand-independent degradation of AhR was insensitive to MG132, suggesting that the 26S proteasome was not responsible for the degradation. In addition, MG132 could not protect AhR from the ligand-induced degradation in both mouse and human p23-knockdown stable cells.
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