Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Sci. Signal., 13 July 2010
Vol. 3, Issue 130, p. ra52
[DOI: 10.1126/scisignal.2000762]

RESEARCH ARTICLES

Regulation of Notch1 Signaling by Nrf2: Implications for Tissue Regeneration

Nobunao Wakabayashi1*{dagger}, Soona Shin2, Stephen L. Slocum3, Elin S. Agoston2{ddagger}, Junko Wakabayashi1§, Mi-Kyoung Kwak4, Vikas Misra1||, Shyam Biswal1, Masayuki Yamamoto5, and Thomas W. Kensler1,2*

1 Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
2 Department of Pharmacology and Molecular Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
3 Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
4 College of Pharmacy, Yeungnam University, 214-1 Dae-dong, Gyeongsan-si, Gyeongsangbuk-do 712-749, South Korea.
5 Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, 2-1 Seiryo-cho, Aoba-ku, Sendai 980-8575, Japan.

* Present address: Department of Pharmacology and Chemical Biology, BSTWR E1316, University of Pittsburgh, Pittsburgh, PA 15261, USA.

{ddagger} Present address: Brigham and Women’s Hospital, Department of Pathology, Division of Women’s and Perinatal Pathology, Boston, MA 02115, USA.

§ Present address: Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

|| Present address: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA.

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.

{dagger} To whom correspondence should be addressed. E-mail: nw99{at}pitt.edu

Citation: N. Wakabayashi, S. Shin, S. L. Slocum, E. S. Agoston, J. Wakabayashi, M.-K. Kwak, V. Misra, S. Biswal, M. Yamamoto, T. W. Kensler, Regulation of Notch1 Signaling by Nrf2: Implications for Tissue Regeneration. Sci. Signal. 3, ra52 (2010).

Read the Full Text

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Nrf2 participates in regulating maternal hepatic adaptations to pregnancy.
Y. Zou, M. Hu, Q. Bao, J. Y. Chan, and G. Dai (2013)
J. Cell Sci. 126, 1618-1625
   Abstract »    Full Text »    PDF »
Identification of novel NRF2-regulated genes by ChIP-Seq: influence on retinoid X receptor alpha.
B. N. Chorley, M. R. Campbell, X. Wang, M. Karaca, D. Sambandan, F. Bangura, P. Xue, J. Pi, S. R. Kleeberger, and D. A. Bell (2012)
Nucleic Acids Res. 40, 7416-7429
   Abstract »    Full Text »    PDF »
Minocycline-Preconditioned Neural Stem Cells Enhance Neuroprotection after Ischemic Stroke in Rats.
H. Sakata, K. Niizuma, H. Yoshioka, G. S. Kim, J. E. Jung, M. Katsu, P. Narasimhan, C. M. Maier, Y. Nishiyama, and P. H. Chan (2012)
J. Neurosci. 32, 3462-3473
   Abstract »    Full Text »    PDF »
Science Signaling Podcast: 20 July 2010.
M. Fainzilber and A. M. VanHook (2010)
Science Signaling 3, pc15
   Abstract »    Full Text »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882