Levy S, Forman HJ

Department of Natural Sciences, University of California, Merced, USA.

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.

Mesh Terms:
Aldehydes, Cell Line, Chromatin Immunoprecipitation, Down-Regulation, E-Box Elements, Glutamate-Cysteine Ligase, Humans, Metabolic Detoxication, Phase II, NF-E2-Related Factor 2, Proto-Oncogene Proteins c-jun, Proto-Oncogene Proteins c-myc, Response Elements, Transcriptional Activation

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