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

doi:10.1126/scisignal.2000762

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

Tohoku Medical Megabank Organization (ToMMo)

Research output: Contribution to journal › Article › peer-review

185 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 language	English
Pages (from-to)	ra52
Journal	Science Signaling
Volume	3
Issue number	130
DOIs	https://doi.org/10.1126/scisignal.2000762
Publication status	Published - 2010 Jul 13

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10.1126/scisignal.2000762

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title = "Regulation of Notch1 signaling by Nrf2: Implications for tissue regeneration",

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.",

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

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T1 - Regulation of Notch1 signaling by Nrf2

T2 - Implications for tissue regeneration

AU - Wakabayashi, Nobunao

AU - Shin, Soona

AU - Slocum, Stephen L.

AU - Agoston, Elin S.

AU - Wakabayashi, Junko

AU - Kwak, Mi Kyoung

AU - Misra, Vikas

AU - Biswal, Shyam

AU - Yamamoto, Masayuki

AU - Kensler, Thomas W.

PY - 2010/7/13

Y1 - 2010/7/13

N2 - 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.

AB - 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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JO - Science Signaling

JF - Science Signaling

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ER -

Regulation of Notch1 signaling by Nrf2: Implications for tissue regeneration

Abstract

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