Regulation of Notch1 signaling by Nrf2: Implications for tissue regeneration

Nobunao Wakabayashi, Soona Shin, Stephen L. Slocum, Elin S. Agoston, Junko Wakabayashi, Mi Kyoung Kwak, Vikas Misra, Shyam Biswal, Masayuki Yamamoto, Thomas W. Kensler

Research output: Contribution to journalArticlepeer-review

139 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)ra52
JournalScience Signaling
Volume3
Issue number130
DOIs
Publication statusPublished - 2010 Jul 13

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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