Regulation of FOXO Factors in Mammalian Cells

Forkhead box O (FOXO) transcription factors are central regulators of cellular homeostasis. FOXOs respond to a wide range of external stimuli, including growth factor signaling, oxidative stress, genotoxic stress, and nutrient deprivation. These signaling inputs regulate FOXOs through a number of posttranslational modifications, including phosphorylation, acetylation, ubiquitination, and methylation. Covalent modifications can affect localization, DNA binding, and interactions with other cofactors in the cell. FOXOs integrate the various modifications to regulate cell type-specific gene expression programs that are essential for metabolic homeostasis, redox balance, and the stress response. Together, these functions are critical for coordinating a response to environmental fluctuations in order to maintain cellular homeostasis during development and to support healthy aging.