Functional Regulation of DNA Binding of FOXO1 by Post Translational Modifications: In silico Study

The transcription factor Forkhead box O 1 (FOXO1) is a key regulator of metabolic processes such as regulation of the cell cycle and cancer. Different post translational modifications (PTMs) such as phosphorylation, glycosylation, acetylation, methylation and ubiquitination control the structure, function regulation and subcellular localization of FOXO1. In this work the role of different modifications and their interplay, involving the regulating the transcriptional activity of FOXO1, is investigated by using various bio-informatic tools. Amongst these is the YinOYang prediction method, which predicts Yin Yang sites in proteins (sites, where O-glycosylation and phosphorylation may compete with each other). Moreover acetylation and methylation may also work together to regulate FOXO1 transcriptional activity. This study suggest that phosphorylation and acetylation deactivate FOXO1's transcriptional activity by disrupting binding between DNA and FOXO1, and promote its cytoplasmic localization and degradation of the FOXO1 transcription factor. Furthermore, glycosylation and methylation increase the DNA binding affinity and enhance nuclear accumulation of FOXO1 and promote transcriptional activity. Thus this in silico work suggests that different modifications play an important role in the regulation of FOXO1's transcriptional activity and its target genes.