The FOXO1 gene is located on chromosome 13 and translates into FOXO1 protein, which contains 4 functional domains, including the nuclear localization signal domain (NLS), the nuclear export signal (NES), the transactivation domain (TA) and the Forkhead domain (FKH). FOXO1 modulates numerous targets, such as genes involved in apoptosis and autophagy, anti-oxidative enzymes, cell cycle arrest genes, and metabolic and immune regulators, rendering it a super transcription factor with complex activities. A wide range of upstream factors affect the translation of FOXO1 or connect to the FOXO1 protein to constitute signalling pathways that regulate FOXO1’s transcriptional activity in many key biological processes. 
The prominent role of FOXO1 signalling in apoptosis and cell cycle arrest depends on the expression of its targets, such as Puma, Bim, Fas ligand (Fasl), GADD45, p21, p27, and Cyclin D1/2. FOXO1 modulates the metabolism of adipose and glucose by augmenting the expression of autophagy factors and key enzymes of gluconeogenesis, such as Rab7, Fat specific protein 27 (FSP27), transcription factor EB (Tfeb), mitochondrial uncoupling proteins (UCPs), Phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase). FOXO1 signalling cascade also contributes to the downregulation of innate TLR4 activation and inflammatory responses. Comprehensively, overexpression and loss of FOXO1 both have been described as possessing regulatory effects on the function of its targets, making them hot subjects of intense investigation, which is conducted in the research arena of cancer, myeloid leukaemia, metabolic disorders, immunity and other disease processes.


1.Xing YQ,et al. Life Sci. 2018;193:124–131.