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KMID : 1140220140190020111
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2014 Volume.19 No. 2 p.111 ~ p.117
Targeting Nrf2 Signaling to Combat Chemoresistance
No Jae-Hong

Kim Yong-Beom
Song Yong-Sang
Abstract
Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor that upregulates expression of a battery of genes to combat oxidative and electrophilic stress. Modification of Kelch-like ECH-associated protein 1 (Keap1) by reactive oxygen species stabilizes Nrf2 by escaping from degradation. Nrf2 then binds to antioxidant response elements (AREs) on the promoter region of various genes. Activation of the Keap1-Nrf2-ARE pathway plays critical roles in the chemopreventive effect of various phytochemicals. However, Nrf2 can protect cancer cells from oxidative stress and promote cell proliferation. Moreover, recent studies reveal that activation of the Nrf2 pathway is critical for resistance to chemotherapeutic agents. The aim of this review is to provide a molecular basis for the use of Nrf2 inhibitors in overcoming chemoresistance.
KEYWORD
Nrf2, Keap1, Chemotherapy, Inhibitor
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