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

研究成果: Article査読

150 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)ra52
ジャーナルScience Signaling
3
130
DOI
出版ステータスPublished - 2010 7 13

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 細胞生物学

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