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Fig. 3 | Cell Communication and Signaling

Fig. 3

From: Dual roles and therapeutic potential of Keap1-Nrf2 pathway in pancreatic cancer: a systematic review

Fig. 3

The Keap1-Nrf2 signaling pathway. Under normal physiological conditions, the Nrf2 protein level is tightly controlled by Keap1. Keap1 dimerizes through the N-terminal BTB domain and forms E3 ubiquitin ligase complexes with Cullin3 (Cul3) and Ring box protein-1 (RBX1), then promoting Nrf2 ubiquitination and degradation. Nrf2 is also negatively regulated by the E3 ubiquitin ligase complexes, the β-TrCP-SKP1-Cullin1 (Cul1)-RBX1 and HRD1. When cells are exposed to electrophiles or ROS or under endoplasmic reticulum (ER) stress, the Nrf2 protein level is increased. Nrf2 then translocates into the nucleus, forms heterodimers with sMAF proteins, binds to the antioxidant response elements (AREs), and then activates the transcription of ARE-driven genes. p62 also interacts with the Nrf2-binding site on Keap1 and releases Nrf2 from Keap1-mediated protein degradation

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