期刊
IUBMB LIFE
卷 62, 期 3, 页码 237-246出版社
WILEY
DOI: 10.1002/iub.314
关键词
c-Myc; Nrf2; EpRE; phase II genes
资金
- National Institutes of Health [ES 05511]
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 downregulated transcription and promoter activity of phase II genes. Chromatin immunoprecipitation verified binding of c-Myc to EpRE while coimmunoprecipitation 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. (C) 2010 IUBMB IUBMB Life, 62(3): 237-246, 2010
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