The role of FOXO transcription factors in the cellular response to stress

Abstract

Through the regulation of a wide range of target genes, Forkhead box O transcription factors (FOXO) are at the centre of a regulating network for a variety of cellular programs like cell cycle arrest, apoptosis, stress resistance, and metabolism. Other processes involving angiogenesis, immune system function, stem cell preservation and diseases like cancer and diabetes are regulated by FOXOs as well. Many of these processes have been implicated to be malfunctioning in cancer. The activity of FOXO factors is primarily regulated by post-translational modifications (PTM). These PTM's can be formed under the influence of cellular stress like reactive oxygen species (ROS), genotoxic stress, nutrient deprivation and cytokine withdrawal. These types of stress are assumed to accelerate ageing and carcinogenesis. FOXOs help to couteract cellular stress by activating its target genes involved in stress resistance. Therefore, this FOXO feedback loop is associated with life-span and cancer. However, countless mechanisms involved in FOXO signaling remain to be elucidated.