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The Keap1-Nrf2 pathway. Under basal conditions, Keap1 is bound to Nrf2, and Nrf2 is ubiquitinated by the Cul3 E3 ubiquitin ligase for degradation by the proteasome. Upon oxidative stress, sensor cysteines in Keap1 are modified by ROS, leading to Nrf2 stabilization, accumulation, and translocation to the nucleus where Nrf2 heterodimerizes with sMaf and binds to the ARE to activate the transcription of antioxidant genes.
