FOXO1 + FOX3 + FOX4 belong to the forkhead family of transcription factors.FOXO1 (FKHR or ForkHead in Rhabdomyosarcoma) is a 70 kDa protein. Recent studies have shown that this protein can act as either a coactivator or a corepressor of nuclear receptor activity. This action is mediated through the LXXLL motif found in the C terminus of the FOXO1A protein. The specific function of the gene has not yet been determined.FOX3 probably functions as a trigger for apoptosis through expression of genes necessary for cell death. Translocation of the FOXO3 gene with the MLL gene is associated with secondary acute leukemia.FOX4 is a forkhead transcription factor involved in the regulation of the insulin signaling pathway. It binds to insulin-response elements (IREs) and can activate transcription of IGFBP1. FOXO4 down-regulates expression of HIF1A and suppresses hypoxia-induced transcriptional activation of HIF1A-modulated genes. It is also involved in negative regulation of the cell cycle.