Nrf2 and Notch Signaling in Lung Cancer: Near the Crossroad

Figure 2

Keap1/Nrf2 axis in lung cancer. Under basal conditions (green arrow), Nrf2 is sequestered in the cytoplasm by the Keap1-Cul3 complex and rapidly degraded in the ubiquitin-proteasome dependent manner. This Keap1-mediated degradation activity requires two reactive cysteine residues of Keap1, located into the IVR domain. Upon stress stimuli (orange arrow), modification of these cysteine residues of Keap1 inhibits ubiquitin conjugation to Nrf2 by the Keap1-Cul3 complex, thereby provoking Nrf2-Keap1 impairment and resulting in the nuclear accumulation of de novo synthesized Nrf2 protein and enhancement of target genes transcription.