What we know: It's been established that keap1 is involved in the regulation of transcription factor Nrf2, facilitating its ubiquitination and degradation in basal conditions (either by sequestering in the cytoplasm or actively shuttling it out the nuclei). When oxidative stress triggers a change in this mechanism Nrf2 migrates to the nuclei, where is binds the antioxidant response element (ARE), an upstreaming promoter region of many antioxidative, drug-metabolising and cytoprotective genes. This seems to be fairly well established.

But it gets more complicated than that: It appears that to do this Nrf2 requires dimerisation with other proteins containing bzip complexes. I had read that small Maf proteins were normally involved in this activation of ARE. However, I have recently come across a different model that suggests that Maf proteins actually inhibit expression of this genes and it is binding of Nrf2 to other bzip-containing factors that leads to upregulation (I've attached the model, from the NCI's cancer genome anatomy project, below).

Confusing models: Most of the literature I've found supports the opposing idea of the Nrf2-Maf dimers having an upregulating effect. Are these just different models? Has one premise been proven valid over the other? Or have I simply misunderstood this? If anyone has a better grasp of this than myself any comments would be great.

Thanks!