FOXO1: A Potential Target for Human Diseases

Huarui      Lu; Haojie      Huang

Abstract

The forkhead box O (FoxO) transcription factors are known to be involved in many physiological and pathological processes including apoptosis, cell cycle arrest, stress resistance, glucose metabolism, cellular differentiation and development, and tumor suppression. The environmental cues, such as growth factors, nutrients, oxidative stress and irradiation, can either positively or negatively modulate FoxO proteins; activities, thereby ensuring distinctive transcription programs in the cell. The potent activities of FoxOs are tightly controlled by multiple mechanisms, which include posttranslational modification such as phosphorylation, acetylation, methylation and ubiquitination, subcellular localization, and direct protein-protein interaction. Mounting evidence suggests that the human FOXO1 protein, a founding member of the FoxO family is likely involved in carcinogenesis, diabetes and other human diseases. Here we give an overview of most recent findings regarding the regulation and function of FoxO1, its potential role in human diseases and useful animal models for functional studies on FoxO1. Prospective ways in which the discoveries from the basic research of FoxO1 can be utilized for drug targeting and development of novel therapeutics for human diseases are also discussed.

Keywords: FoxO transcription factors, posttranslational modification, apoptosis, the cell cycle, glucose metabolism, cancer, diabetes, muscle atrophy, upstream signaling pathways, STAT3, TRAIL, Dorsophila, C. elegans, pyruvate dehydrogenase kinase 4, alveolar rhabdomyosarcoma