ReIB, a new partner of aryl hydrocarbon receptor-mediated transcription
ReIB, a new partner of aryl hydrocarbon receptor-mediated transcription
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DOI：
10.1210/me.2007-0211
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发表时间：
2007-12-01
影响因子：
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通讯作者：
Matsumura, Fumio
中科院分区：
文献类型：
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作者：
Vogel, Christoph F. A.;Sciullo, Eric;Matsumura, Fumio
核因子-κ B（NF-κ B）转录因子家族在对应激和病原体的快速反应中具有关键作用。我们发现NF-κ B亚基ReIB在功能上与芳烃受体（AhR）相关，并通过激活AhR和蛋白激酶A介导趋化因子如IL-8的转录。ReIB与AhR物理相互作用并结合IL-8启动子的未识别的ReIB/AhR应答元件，其连接两个信号传导途径以激活基因转录。我们发现AhR通过AhR配体2，3，7，8-四氯二苯并-p-二恶英（二恶英）介导并通过蛋白激酶A的活化而被时间依赖性地募集到IL-8的ReIB/AhR反应元件位点。此外，优先被ReIB/p52识别的NF-κ B结合位点是ReIB/AhR复合物的靶点，而不添加任何刺激，这暗示了AhR的内源性功能。ReIB/AhR复合物也被发现与异源反应元件结合，并且ReIB显著增加2，3，7，8-四氯二苯并-p-二恶英诱导的异源反应元件报告活性。ReIB与AhR信号通路以及AhR与NF-κ B ReIB信号通路的相互作用代表了两种转录因子之间的新的串扰机制。
The nuclear factor-kappa B (NF-kappa B) transcription factor family has a crucial role in rapid responses to stress and pathogens. We show that the NF-kappa B subunit ReIB is functionally associated with the aryl hydrocarbon receptor (AhR) and mediates transcription of chemokines such as IL-8 via activation of AhR and protein kinase A. ReIB physically interacts with AhR and binds to an unrecognized ReIB/AhR responsive element of the IL-8 promoter linking two signaling pathways to activate gene transcription. We found a time-dependent recruitment of AhR to the ReIB/AhR responsive element site of IL-8 mediated by the AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin ( dioxin) and via activation of protein kinase A. Furthermore, NF-kappa B-binding sites that are preferentially recognized by ReIB/p52 are a target for ReIB/AhR complexes without addition of any stimuli, implicating the endogenous function of the AhR. ReIB/AhR complexes are also found to bind on xenobiotic responsive element, and ReIB drastically increases the 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced xenobiotic responsive element reporter activity. The interaction of ReIB with AhR signaling, and AhR with NF-kappa B ReIB signaling pathways represent a new mechanism of cross talk between the two transcription factors.