Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway - PubMed (original) (raw)
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Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway
Thomas W Kensler et al. Annu Rev Pharmacol Toxicol. 2007.
Abstract
Keap1-Nrf2-ARE signaling plays a significant role in protecting cells from endogenous and exogenous stresses. The development of Nrf2 knockout mice has provided key insights into the toxicological importance of this pathway. These mice are more sensitive to the hepatic, pulmonary, ovarian, and neurotoxic consequences of acute exposures to environmental agents and drugs, inflammatory stresses, as well as chronic exposures to cigarette smoke and other carcinogens. Under quiescent conditions, the transcription factor Nrf2 interacts with the actin-anchored protein Keap1, largely localized in the cytoplasm. This quenching interaction maintains low basal expression of Nrf2-regulated genes. However, upon recognition of chemical signals imparted by oxidative and electrophilic molecules, Nrf2 is released from Keap1, escapes proteasomal degradation, translocates to the nucleus, and transactivates the expression of several dozen cytoprotective genes that enhance cell survival. This review highlights the key elements in this adaptive response to protection against acute and chronic cell injury provoked by environmental stresses.
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- R01 HL081205-03/HL/NHLBI NIH HHS/United States
- P50 CA 058184/CA/NCI NIH HHS/United States
- AG 24318/AG/NIA NIH HHS/United States
- CA 39416/CA/NCI NIH HHS/United States
- CA 94076/CA/NCI NIH HHS/United States
- R01 HL081205/HL/NHLBI NIH HHS/United States
- HL 081205/HL/NHLBI NIH HHS/United States
- R01 HL081205-02/HL/NHLBI NIH HHS/United States
- P30 ES 03819/ES/NIEHS NIH HHS/United States
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