Figure 5: Activation of transcription factors by external and internal stress reponses (Nrf2). Reactive oxygen species modify central cysteine species on Keap-1 that leads to the decoupling of Keap-1 and Nrf2. Alternatively, Nrf2 can be phosphorylated by kinases. In turn, Nrf2 is decoupled from Keap-1 and translocates to the nucleus where it binds Maf, JunD, or ATF4 and initiates transcription of a variety of antioxidant enzymes and transporters.