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C‐Myc is a Nrf2‐interacting protein that negatively regulates phase II genes through their electrophile responsive elements
Author(s) -
Levy Smadar,
Forman Henry Jay
Publication year - 2010
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.314
Subject(s) - chromatin immunoprecipitation , transcription factor , promoter , immunoprecipitation , transcription (linguistics) , microbiology and biotechnology , response element , proto oncogene proteins c myc , chemistry , dna binding protein , gene , biology , gene expression , biochemistry , linguistics , philosophy
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. © 2010 IUBMB IUBMB Life, 62(3): 237–246, 2010