Regulation of subcellular localization of the aryl hydrocarbon receptor (AhR).
Regulation of subcellular localization of the aryl hydrocarbon receptor (AhR).
复制标题
芳烃受体 (AhR) 亚细胞定位的调节。
DOI：
10.1006/abbi.2001.2339
复制
发表时间：
2001
影响因子：
3.9
通讯作者：
Hannink,M
中科院分区：
文献类型：
--
作者：
Richter,CA;Tillitt,DE;Hannink,M
芳烃受体（AhR）是一种配体激活的转录因子，介导二恶英和其他外源性物质的毒性。在不存在外源配体的情况下，AhR是胞质的。我们研究了AhR是如何保留在胞质溶胶和二恶英如何诱导AhR移动到细胞核。核输出抑制剂来普霉素B（LMB）或突变的AhR核输出信号的AhR的核输出中断导致在无外源性配体的情况下AhR的核积累。AhR核定位信号的突变导致在外源性配体的存在和不存在下AhR的核输入缺陷。二恶英处理导致AhR在细胞核中的积累比LMB处理更快。在二恶英和LMB的存在下，AhR的核积累比单独存在二恶英更快。我们的研究结果表明，AhR穿梭于细胞核和胞质溶胶之间的外源性配体的情况下。配体的结合可诱导AhR的核输入速率增加，但不会消除AhR的核输出。
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates the toxicity of dioxin and other xenobiotics. In the absence of exogenous ligand, AhR is cytosolic. We investigated how AhR is retained in the cytosol and how dioxin induces AhR to move to the nucleus. Disruption of nuclear export of AhR by the nuclear export inhibitor leptomycin B (LMB) or by mutation of the AhR nuclear export signal resulted in nuclear accumulation of AhR in the absence of exogenous ligand. Mutation of the AhR nuclear localization signal resulted in defects in nuclear import of AhR in both the presence and the absence of exogenous ligand. Dioxin treatment caused a more rapid accumulation of AhR in the nucleus than LMB treatment. In the presence of both dioxin and LMB, nuclear accumulation of AhR was more rapid than in the presence of dioxin alone. Our results show that AhR shuttles between the nucleus and the cytosol in the absence of exogenous ligand. Binding of ligand induces an increase in the rate of nuclear import of AhR but does not eliminate nuclear export of AhR.