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This interaction is mediated by dual binding, with FHD mainly binding to the p53 TAD and FOXO4 CR3 binding to the p53 DNA-binding domain (DBD) 38 (Figure

In contrast, the tumor suppressor p53 enhances mitochondrial metabolism and OXPHOS by promoting the assembly of cytochrome oxidase (COX) and glycolytic enzymes

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Given the unique risk of SAEs due to the potential for increased incidence of COVID-19 over the study period, we will also perform a sensitivity analysis where COVID-19 related SAEs will be excluded from the analysis