Figure 1

Pathway scheme. (A) Homodimers of Keap1 (shown in blue) are able to bind the ETGE (high affinity or hinge binding) and the DLG (low affinity or latch binding) motifs of Nrf2 (shown in green). When both Nrf2 motifs are bound, Keap1 can target Nrf2 for proteasomal degradation. p62 (shown in orange) is able to compete with Nrf2 for its latch binding to Keap1, resulting in autophagosomal degradation of Keap1. Upon oxidative stress (yellow arrow), Keap1 is no longer able to target Nrf2 for proteasomal degradation by lack of binding of the DLG motif. This results in nuclear accumulation of Nrf2 and target gene transcription including SRXN1, NQO1, HMOX1 and GLCM (shown in purple). In addition, oxidative stress is reduced via GSH (shown in yellow). (B) Scheme explaining the considered target gene expression of Nrf2 upon oxidative stress. Reactions between the constituents are represented by arrows. They are translated into differential equations for the quantitative model.