C-Myc is a Nrf2-interacting protein that negatively regulates phase II genes through their electrophile responsive elements.

C-Myc is a Nrf2-interacting protein that negatively regulates phase II genes through their electrophile responsive elements.
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DOI:
10.1002/iub.314
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发表时间:
2010-03
期刊:
影响因子:
4.6
通讯作者:
Forman, Henry Jay
Forman, Henry Jay
中科院分区:
生物学3区
文献类型:
--
作者:
Levy, Smadar;Forman, Henry Jay

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c-Myc是一种转录因子,参与许多细胞过程,包括增殖、凋亡和癌症。最近,c-Myc被证明通过E-box序列参与谷氨酸半胱氨酸连接酶的调节。本研究探讨了c-Myc是否也通过与亲电反应元件(EpRE)的相互作用来调节II期基因。在人支气管上皮细胞中使用si-RNA敲低c-Myc进行实验。RT-PCR和报告基因分析用于测量转录和启动子活性。c-Myc下调II期基因的转录和启动子活性。染色质免疫沉淀证实了c-Myc与EpRE的结合,而免疫共沉淀证实了c-Myc与Nrf 2的相互作用。c-Myc还与Nrf 2和p-c-Jun. Finally形成三元复合物,c-Myc降低了Nrf 2的稳定性。因此,我们的研究结果表明,通过与EpRE结合复合物的相互作用和增加Nrf 2的降解,c-Myc的EpRE/Nrf 2信号通路的调节。
c-Myc is a transcription factor that is implicated in many cellular processes including proliferation, apoptosis and cancers. Recently, c-Myc was shown to be involved in regulation of glutamate cysteine ligase through E-box sequences. This investigation examined whether c-Myc also regulates phase II genes through interaction with the electrophile response element (EpRE). Experiments were conducted in human bronchial epithelial cells using si-RNA to knock down c-Myc. RT-PCR and reporter assays were used to measure transcription and promoter activity. c-Myc down-regulated transcription and promoter activity of phase II genes. Chromatin immunoprecipitation verified binding of c-Myc to EpRE while co-immunoprecipitation demonstrated interaction of c-Myc with Nrf2. c-Myc also forms a ternary complex with Nrf2 and p-c-Jun. Finally, c-Myc decreased Nrf2 stability. Thus, our results suggest regulation of the EpRE/Nrf2 signaling pathway by c-Myc through both interaction with the EpRE binding complex and increased degradation of Nrf2.
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