High-throughput image-based screening to identify chemical compounds capable of activating FOXO

Abstract

FOXO proteins are transcription factors with important roles in the regulation of the expression of genes involved in cell growth, proliferation, differentiation, and longevity. FOXO proteins are active in the nucleus but, upon post-translational modification they form a docking site for 14-3-3 proteins and are translocated to the cytoplasm where they are inactive. We make use of this regulatory mechanism of FOXO proteins to develop an image-based high-throughput screening platform to detect compounds that regulate FOXO3 subcellular localization. This system has proven a powerful tool to isolate inhibitors of proteins upstream of FOXO, such as PI3K inhibitors.