The mechanism of AH receptor protein down-regulation (degradation) and its impact on AH receptor-mediated gene regulation
The mechanism of AH receptor protein down-regulation (degradation) and its impact on AH receptor-mediated gene regulation
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DOI：
10.1016/s0009-2797(02)00065-0
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发表时间：
2002-09-20
影响因子：
5.1
通讯作者：
Pollenz, RS
中科院分区：
文献类型：
--
作者：
Pollenz, RS
转录因子的蛋白水解降解是调节信号转导途径的既定机制。最近的报告表明，芳烃受体（AHR）蛋白在配体结合后迅速下调（降解）。AHR的下调已被观察到在9个不同的细胞培养系来自人类和啮齿动物组织，也已被观察到在啮齿动物模型暴露于2，3，7，8-四氯二苯并-p-二恶英（TCDD）。AHR的下调似乎是由泛素介导的，并通过AHR核输出后的26 S蛋白酶体途径发生。在细胞培养中阻断AHR降解的结果似乎是AHR基因调控的幅度和持续时间增加（.）ARNT复合体。因此，AHR降解的生理作用可能是调节AHR介导的基因调控。本文综述了AHR在体内和体外降解的研究分析，并提出了AHR下调在AHR介导的基因调控衰减中至关重要的假设。(C)2002爱思唯尔科学爱尔兰有限公司保留所有权利。
The proteolytic degradation of transcription factors is an established mechanism of regulating signal transduction pathways. Recent reports have Suggested that the aryl hydrocarbon receptor (AHR) protein is rapidly downregulated (degraded) following ligand binding. The downregulation of AHR has been observed in nine distinct cells culture lines derived from human and rodent tissues and has also been observed in rodent models following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The downregulation of AHR appears to be ubiquitin mediated and occurs via the 26S proteasome pathway following nuclear export of AHR. The consequence of blocking AHR degradation in cell culture appears to be an increase in both the magnitude and duration of gene regulation by the AHR(.)ARNT complex. Thus, the physiological role of AHR degradation may be to modulate AHR-mediated gene regulation. This review provides analysis of the studies that have focused on the degradation of AHR in vivo and in vitro and the hypothesis that the downregulation of AHR is critical in the attenuation of AHR-mediated gene regulation. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.