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.

中文翻译：

---

细胞存活通过Keap1-Nrf2-ARE途径对环境胁迫的反应。

Keap1-Nrf2-ARE信号传导在保护细胞免受内源性和外源性胁迫中起重要作用。Nrf2基因敲除小鼠的发展提供了对该途径的毒理学重要性的关键见解。这些小鼠对急性暴露于环境剂和药物，炎症应激以及长期暴露于香烟烟雾和其他致癌物的肝，肺，卵巢和神经毒性后果更为敏感。在静态条件下，转录因子Nrf2与肌动蛋白锚定的蛋白Keap1相互作用，该蛋白主要位于细胞质中。这种淬灭相互作用维持了Nrf2调节基因的低基础表达。但是，在识别出由氧化性和亲电性分子传递的化学信号后，Nrf2从Keap1中释放出来，逃脱了蛋白酶体降解，易位到细胞核，并激活数十种增强细胞存活的细胞保护性基因的表达。这篇综述强调了这种对环境压力引起的对急性和慢性细胞损伤的保护的适应性反应中的关键要素。