Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
Curr Drug Targets. 2011 Aug;12(9):1235-44. doi: 10.2174/138945011796150280.
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.
叉头框 O（FoxO）转录因子已知参与许多生理和病理过程，包括细胞凋亡、细胞周期阻滞、应激抵抗、葡萄糖代谢、细胞分化和发育以及肿瘤抑制。环境线索，如生长因子、营养物质、氧化应激和辐射，可以正向或负向调节 FoxO 蛋白的活性，从而确保细胞中独特的转录程序。FoxO 的强大活性受到多种机制的严格控制，包括翻译后修饰（如磷酸化、乙酰化、甲基化和泛素化）、亚细胞定位和直接蛋白质-蛋白质相互作用。越来越多的证据表明，FoxO 家族的创始成员之一人类 FOXO1 蛋白可能参与癌症发生、糖尿病和其他人类疾病。在这里，我们概述了关于 FoxO1 调节和功能的最新发现，及其在人类疾病中的潜在作用，以及用于 FoxO1 功能研究的有用动物模型。还讨论了如何利用 FoxO1 的基础研究发现，为人类疾病的药物靶向和新型治疗方法的开发提供新的途径。
