Fig. 2.

Scheme of Keap1-Nrf2 interactions. Under homeostatic conditions, Nrf2 is bound by Keap1 through the “hinge” ETGE) and “latch” (DLG) domains of Nrf2. Upon association, Nrf2 is ubiquitinated by the Cul2/Rbx1/E2 ubiquitin ligaase complex, marking it for proteasomal degradation. Induction of Nrf2 signaling by sulforaphane through thiocarbamylation at Cys 151may lead to disruption of the Cul3 association with Keap1 and abrogation of Nrf2 ubiquitination. Newly synthesized Nrf2 thereby escapes proteasomal degradation and translocates to the nucleus where it accumulates and activates the transcription of its target genes.