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Molecules 2014, 19(7), 10074-10089; doi:10.3390/molecules190710074
Review

Molecular and Chemical Regulation of the Keap1-Nrf2 Signaling Pathway

1,*  and 2,*
Received: 11 May 2014; in revised form: 2 June 2014 / Accepted: 2 July 2014 / Published: 10 July 2014
(This article belongs to the Special Issue Natural Antioxidants and Ageing)
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Abstract: Extracellular and intracellular oxidants or electrophiles are key contributors to the damages in cellular macromolecules, such as DNA, proteins and lipids. Nrf2 is a master transcription factor that modulates a cellular antioxidant response program and plays an important role in the protection against oxidants and electrophiles. Keap1 is a regulator of Nrf2 by serving as a substrate adaptor for Cullin3-dependent E3 ubiquitin ligase. While Nrf2 activation is a feasible strategy for treatment of age-related diseases, aberrant Nrf2 activation also confers a selective growth advantage of tumor cells during chemotherapy or radiotherapy. In the present review, we provide an overview of the Keap1-Nrf2-ARE system, the domain organization of Nrf2 and Keap1, and the regulatory mechanisms of Nrf2 proteolysis by Keap1. We also discuss how Nrf2 prevents tumor promotion, hampers the sensitivity of selected tumors against chemotherapy or radiotherapy, and reprograms the metabolism to facilitate the tumor proliferation. Finally, we illustrate the current status in the development of Nrf2 chemical activators and inhibitors for the use of potential chemopreventive agents and chemotherapeutic adjuvants, respectively.
Keywords: Keap1; Nrf2; ARE; oncogene; tumor suppressor gene; metabolism Keap1; Nrf2; ARE; oncogene; tumor suppressor gene; metabolism
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Keum, Y.-S.; Choi, B.Y. Molecular and Chemical Regulation of the Keap1-Nrf2 Signaling Pathway. Molecules 2014, 19, 10074-10089.

AMA Style

Keum Y-S, Choi BY. Molecular and Chemical Regulation of the Keap1-Nrf2 Signaling Pathway. Molecules. 2014; 19(7):10074-10089.

Chicago/Turabian Style

Keum, Young-Sam; Choi, Bu Y. 2014. "Molecular and Chemical Regulation of the Keap1-Nrf2 Signaling Pathway." Molecules 19, no. 7: 10074-10089.


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