An interaction between Nrf2 and FOXO transcription factors (be it functional or even physical) would therefore make sense, and such interaction was indeed described in the literature (for review, see [25]); for example, it was demonstrated in human tumor cell lines cells that FOXO3 stimulates the transcription of the Keap-1 gene [29], regulating Keap-1 protein levels; FOXO3 would thus attenuate Nrf2 action by elevating Keap-1 levels, whereas FOXO inactivation (e.g. through insulin-induced activation of Akt) would tend to stimulate Nrf2. The gene discussed is FOXO3; the disease is neoplasm.