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. 2022 Dec 28;28(48):6909–6921. doi: 10.3748/wjg.v28.i48.6909

Figure 2.

Figure 2

Kelch-like ECH-associated protein 1-independent nuclear factor-erythroid 2 signaling. During oxidative stress, selective autophagy substrate p62 competes with nuclear factor-erythroid 2 (NRF2) to bind with kelch-like ECH-associated protein 1 (Keap1). As a consequence, NRF2 dissociates from Keap1 and translocates to the nucleus to induce target genes. Glycogen synthase kinase 3β (GSK-3β) phosphorylates the NRF2 subunit Nrf-ECH homology (Neh) 6, leading to degradation by β-transducin repeats containing protein (β-TrCP). Phosphatidylinositol 3’-kinase-protein kinase B (AKT) signaling could inhibit GSK-3β. Protein kinase C phosphorylates Ser40 in Neh2, inducing NRF2 translocation to the nucleus. ARE: Antioxidant responsive element; SMaf: Small musculoaponeurotic fibrosarcoma oncogene homologue.