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Updated: Apr 12, 2026
05:48
Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands
Published on: January 2, 2018
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Crosstalk between Nrf2 and Notch signaling
Nobunao Wakabayashi1, Dionysios V Chartoumpekis1, Thomas W Kensler2
1Department of Pharmacology & Chemical Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Free Radical Biology & Medicine
|May 25, 2015
Summary
The transcription factor Nrf2 and Notch signaling pathways are reciprocally regulated, impacting adult liver function and development. This crosstalk is crucial for maintaining cellular homeostasis under stress.
Area of Science:
- Molecular Biology
- Cellular Biology
- Genetics
Background:
- Nuclear factor, erythroid derived 2, like 2 (Nrf2) is a transcription factor regulating cellular responses to stress via antioxidant response elements (AREs).
- Notch signaling, involving transmembrane receptors and transcription factors like Rbpjκ, plays a role in liver development and function.
- Previous studies indicated decreased Notch1 and related gene expression in Nrf2-disrupted cells, suggesting a potential crosstalk.
Purpose of the Study:
- To investigate the reciprocal transcriptional regulation between Nrf2 and Notch signaling pathways.
- To elucidate the role of this crosstalk in adult liver homeostasis and development.
Main Methods:
- Gene expression microarray analyses comparing Nrf2-disrupted and wild-type mouse embryonic fibroblasts.
- Identification of functional AREs upstream of Notch1.
- Analysis of conserved Rbpjκ binding sites on Nrf2 promoters.
- Utilizing genetically engineered mice (Nrf2, Keap1, Notch1 knockout models).
Main Results:
- A functional ARE was identified upstream of the Notch1 transcription start site.
- Conserved Rbpjκ binding sites were found on Nrf2 promoters, indicating a conserved regulatory mechanism.
- Reciprocal transcriptional regulation between Nrf2 and Notch pathways was confirmed in adult liver studies.
Conclusions:
- Nrf2 and Notch signaling pathways exhibit reciprocal transcriptional regulation.
- This crosstalk is important for adult liver development and the maintenance of hepatic function.
- Understanding this interaction provides insights into cellular homeostasis and stress response mechanisms.
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