Abstract
A few studies have clearly indicated that oxidative stress suppresses the cystic fibrosis transmembrane conductance receptor (CFTR) function and expression. However, the mechanisms by which this occurs are still poorly understood. To clarify this effect, we investigated the role of NF-E2-related factor 2 (Nrf2) transcription factor, a key cellular sensor of oxidative stress. A conserved antioxidant response element (ARE) in the CFTR minimal promoter, which binds Nrf2, has been identified. Surprisingly, Nrf2 exerts an unexpected repressive role on the CFTR gene promoter activity. To decipher the molecular mechanisms involved, we evaluated the role of YY1 in the Nrf2-mediated transcriptional activity and showed cooperation between these two factors. We demonstrated that Nrf2 promotes YY1 nuclear localization and increases its binding to the CFTR promoter. To our knowledge, this study is the first to report a repressor role of Nrf2 through the cooperation with YY1 and contributes to clarify the cascade events leading to the oxidative stress-suppressed CFTR expression.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
