Potential Applications of NRF2 Inhibitors in Cancer Therapy

Figure 2

General mechanism of NRF2/KEAP1 control and function. (a) Under homeostatic conditions, KEAP1 interacts with NRF2 in the cytosol, promoting its polyubiquitylation and subsequent proteasomal degradation, resulting in minimal or absent NRF2 transactivation. (b) In contrast, under different stress conditions, the binding of KEAP1 to NRF2 is strongly impaired, decreasing the likelihood of NRF2 ubiquitylation. As a consequence, a large fraction of NRF2 molecules in the cytosolic pool can translocate into the nucleus, wherein it interacts with small MAF proteins and induces the transcription of several cytoprotective genes.

(a)

(b)