p62 links autophagy and Nrf2 signaling

摘要: The Nrf2-Keap1-ARE pathway is a redox and xenobiotic sensitive signaling axis that functions to protect cells against oxidative stress, environmental toxicants, harmful chemicals through the induction of cytoprotective genes. To enforce strict regulation, invest great deal energy into maintenance Nrf2 ensure rapid upon cellular insult return basal levels once mitigated. Because protective role transcriptional programs, controlled activation has been recognized as means for chemoprevention. On other hand, constitutive Nrf2, due somatic mutations genes control degradation, promotes carcinogenesis imparts chemoresistance cancer cells. Autophagy, bulk protein degradation process, another tightly regulated complex process quality system remove damaged proteins or organelles. Low nutrient can also activate autophagy, which acts restore metabolic homeostasis macromolecules provide nutrients. Recently, these two pathways were shown intersect direct interaction between p62 (an autophagy adaptor protein) Keap1 (the substrate Cul3 E3 ubiquitin ligase). Dysregulation was result in prolonged p62-dependent manner. In this review, we will discuss progress made dissecting intersection potential tumor-promoting activation.