Figure 3: Nuclear regulation of Nrf2. Nrf2 forms heterodimers with Maf proteins to control differential gene regulation through the antioxidant response element (ARE). Acetylation of Nrf2 by the co-activator p300/CBP increased binding of Nrf2 to promoters in the ARE. Deacetylation by SIRT1 and other class I HDACs disengages Nrf2 from the ARE, thereby terminating transcription. Upon disengagement from the ARE, Fyn phosphorylates Tyr568 of Nrf2, resulting in Keap1 independent nuclear export via Crm1. Nrf2 can also complex with Keap1-Cul3-Rbx1, which is then ubiquitinated, exported, and degraded by the proteasome.