Abstract
Nuclear translocation of EGFR has been shown to be important for tumor cell growth, survival, and therapeutic resistance. Previously, we detected the association of EGFR with Keap1 in the nucleus. Keap1 is a Kelch-like ECH-associated protein, which plays an important role in cellular response to chemical and oxidative stress by regulating Nrf2 protein stability and nuclear translocation. In this study, we investigate the role of EGFR in regulating Keap1/Nrf2 cascade in the nucleus and provide evidence to show that nuclear EGFR interacts with and phosphory-lates nuclear Keap1 to reduce its nuclear protein level. The reduction of nuclear Keap1 consequently stabilizes nuclear Nrf2 and increases its transcriptional activity in cancer cells, which contributes to tumor cell resistance to chemotherapy.
Original language | English (US) |
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Pages (from-to) | 649-663 |
Number of pages | 15 |
Journal | American Journal of Translational Research |
Volume | 6 |
Issue number | 6 |
State | Published - 2014 |
Keywords
- Cancer
- EGFR
- Keap1
- Nrf2
- Ubiquitination
ASJC Scopus subject areas
- Molecular Medicine
- Clinical Biochemistry
- Cancer Research