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Updated: Apr 18, 2026

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation
Published on: May 20, 2020
Activation of Keap1/Nrf2 signaling pathway by nuclear epidermal growth factor receptor in cancer cells
Longfei Huo1, Chia-Wei Li1, Tzu-Hsuan Huang1
1Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center 1515 Holcombe Boulevard, Houston, TX 77030.
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 phosphorylates 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.
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