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Publication : Regulation of notch1 signaling by nrf2: implications for tissue regeneration.

First Author  Wakabayashi N Year  2010
Journal  Sci Signal Volume  3
Issue  130 Pages  ra52
PubMed ID  20628156 Mgi Jnum  J:185406
Mgi Id  MGI:5428401 Doi  10.1126/scisignal.2000762
Citation  Wakabayashi N, et al. (2010) Regulation of notch1 signaling by nrf2: implications for tissue regeneration. Sci Signal 3(130):ra52
abstractText  The Keap1-Nrf2-ARE signaling pathway elicits an adaptive response for cell survival after endogenous and exogenous stresses, such as inflammation and carcinogens, respectively. Keap1 inhibits the transcriptional activation activity of Nrf2 (p45 nuclear factor erythroid-derived 2-related factor 2) in unstressed cells by facilitating its degradation. Through transcriptional analyses in Keap1- or Nrf2-disrupted mice, we identified interactions between the Keap1-Nrf2-ARE and the Notch1 signaling pathways. We found that Nrf2 recognized a functional antioxidant response element (ARE) in the promoter of Notch1. Notch1 regulates processes such as proliferation and cell fate decisions. We report a functional role for this cross talk between the two pathways and show that disruption of Nrf2 impeded liver regeneration after partial hepatectomy and was rescued by reestablishment of Notch1 signaling.
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