转录因子NRF2（NF-E2相关因子2）是细胞对环境应激的主要调节因子。NRF2诱导解毒和抗氧化酶的表达，并抑制前炎性细胞因子基因的诱导。KEAP1（Kelch-like ECH相关蛋白1）是CULLIN 3（CUL3） E3泛素连接酶的适配器亚基。KEAP1调节NRF2的活性，作为氧化和电子亲合应激的传感器。NRF2已在许多预后不良的癌症中被激活。控制NRF2过度激活的治疗策略不仅通过靶向NRF2抑制剂或NRF2合成致死化学品靶向癌细胞，而且还通过利用NRF2诱导剂靶向宿主防御。了解KEAP1-NRF2系统如何感知和调节细胞反应的精确分子机制对于克服难治性NRF2激活的癌症至关重要。

Transcription factor NRF2 (NF-E2-related factor 2) is a master regulator of cellular responses against environmental stresses. NRF2 induces expression of detoxification and antioxidant enzymes and suppresses inductions of pro-inflammatory cytokine genes. KEAP1 (Kelch-like ECH-associated protein 1) is an adaptor subunit of CULLIN 3 (CUL3)-based E3 ubiquitin ligase. KEAP1 regulates the activity of NRF2 and acts as a sensor for oxidative and electrophilic stresses. NRF2 has been found to be activated in many types of cancers with poor prognosis. Therapeutic strategies to control NRF2-overeactivated cancers have been considered not only by targeting cancer cells with NRF2 inhibitors or NRF2 synthetic lethal chemicals, but also by targeting host defense with NRF2 inducers. Understanding precise molecular mechanisms how the KEAP1-NRF2 system senses and regulates the cellular response is critical to overcome intractable NRF2-activated cancers.