Target Nuclear Factor Erythroid 2-Related Factor 2 in Pulmonary Hypertension: Molecular Insight into Application

Figure 1

Keap1/Nrf2/ARE signaling pathway. Under unstressed condition, Nrf2 is degraded in Keap1-mediated ubiquitin proteasomal pathway. DLG and ETGE motifs in Nrf2 bind to DC domain of Keap1; the lysine residue between DLG and ETGE motif is the proteasomal degradation target, contributing to the low level of Nrf2 under quiescent conditions. Upon oxidative stress, the cysteine residues on Keap1 are inactivated by Nrf2 inducers, which hinder the degradation of Nrf2 and lead to increased Nrf2 expression. Accumulated Nrf2 translocates to the nucleus and heterodimerizes with sMAF proteins; downstream cytoprotective genes are activated through binding to the antioxidant response elements.