期刊
NATURE COMMUNICATIONS
卷 10, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-019-12925-9
关键词
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资金
- National Key Research and Development Program of China, Stem cell and Translational Research [2018YFA0107200, 2017YFA0103403, 2017YFA0103802]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA16010103, XDA16020701]
- National Natural Science Foundation of China [81425016, 81570593, 81730005, 31771616, 81802402, 81971372]
- Natural Science Foundation of Guangdong Province [2017A030310237]
- Key Research and Development Program of Guangdong Province [2016B030229002, 2017B020231001, 2019B020234001, 2019B020236002, 2019B020235002]
- Key Scientific and Technological Program of Guangzhou City [201803040011, 201704020223]
- Fundamental Research Funds for the Central Universities [19ykpy158, 19ykyjs55, 19ykyjs56, 19ykyjs60]
- China Postdoctoral Science Foundation [2017T100657]
Abnormal cancer antioxidant capacity is considered as a potential mechanism of tumor malignancy. Modulation of oxidative stress status is emerging as an anti-cancer treatment. Our previous studies have found that Nestin-knockdown cells were more sensitive to oxidative stress in non-small cell lung cancer (NSCLC). However, the molecular mechanism by which Nestin protects cells from oxidative damage remains unclear. Here, we identify a feedback loop between Nestin and Nrf2 maintaining the redox homeostasis. Mechanistically, the ESGE motif of Nestin interacts with the Kelch domain of Keap1 and competes with Nrf2 for Keap1 binding, leading to Nrf2 escaping from Keap1-mediated degradation, subsequently promoting antioxidant enzyme generation. Interestingly, we also map that the antioxidant response elements (AREs) in the Nestin promoter are responsible for its induction via Nrf2. Taken together, our results indicate that the Nestin-Keap1-Nrf2 axis regulates cellular redox homeostasis and confers oxidative stress resistance in NSCLC.
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