Based on studies with mouse FOXO proteins, FOXO3 (Rangarajan et al. 2015, Song et al. 2016) and FOXO6 (Kim et al. 2014) bind forkhead box elements in the promoter of the CAT gene, encoding the enzyme catalase. Catalase converts hydrogen peroxide to water and oxygen, thus protecting cells from the oxidative stress. FOXO1 positively regulates CAT gene transcription (Awad et al. 2014, Liao et al. 2016, Guo et al. 2016) and is probably able to bind to forkhead box elements in the CAT gene promoter.
FOXO3-mediated upregulation of the CAT gene transcription is positively regulated by SIRT3 histone deacetylase, which deacetylates FOXO3 under conditions of oxidative stress and increases nuclear localization of FOXO3 (Sundaresan et al. 2009, Rangarajan et al. 2015, Yang et al. 2016).