Regulation of Notch1 Signaling by Nrf2: Implications for Tissue Regeneration

Title
Regulation of Notch1 Signaling by Nrf2: Implications for Tissue Regeneration
Author(s)
곽미경Nobunao Wakabayashi[Nobunao Wakabayashi]Soona Shin[Soona Shin]Stephen L. Slocum[Stephen L. Slocum]Elin S. Agoston[Elin S. Agoston]Junko Wakabayashi[Junko Wakabayashi]Vikas Misra[Vikas Misra]Shyam Biswal[Shyam Biswal]Masayuki Yamamoto[Masayuki Yamamoto]Thomas W. Kensler[Thomas W. Kensler]
Keywords
EMBRYONIC LETHALITY; TRANSCRIPTION FACTORS; LIVER-REGENERATION; TUMOR-SUPPRESSOR; OXIDATIVE STRESS; MAMMALIAN-CELLS; GENE-EXPRESSION; KNOCKOUT MICE; INDUCTION; PATHWAY
Issue Date
201007
Publisher
AMER ASSOC ADVANCEMENT SCIENCE
Citation
SCIENCE SIGNALING, v.3, no.130
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.
URI
http://hdl.handle.net/YU.REPOSITORY/23930http://dx.doi.org/10.1126/scisignal.2000762
ISSN
1937-9145
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약학대학 > 약학부 > Articles
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