Burgering B M Th
Laboratory of Physiological Chemistry, University Medical Center Utrecht, Stratenum, Utrecht, The Netherlands.
Oncogene. 2008 Apr 7;27(16):2258-62. doi: 10.1038/onc.2008.29.
Members of the Forkhead box O (FOXO) class of transcription factors are key players in the regulation of cell-fate decisions, such as cell death, cell proliferation and cell metabolism. Furthermore, in model organisms, it has by now been demonstrated that FOXO function affects the life span of these organisms. Multiple signal transduction pathways regulate FOXO function, but most importantly, they are negatively regulated by protein kinase B (PKB/AKT)-mediated phosphorylation and constitute, therefore, an important downstream component of insulin signalling. This review issue provides a timely overview of our understanding of FOXO function and how signalling affects FOXO function. Taken together, the reviewed studies on FOXO function and regulation provide compelling evidence that FOXOs act at the crossroad between aging and age-related diseases including diabetes and cancer. With this perspective, further studies on FOXO function and regulation may shed light on how age impacts on the onset and progression of disease.
叉头框O（FOXO）转录因子家族成员是细胞命运决定调控的关键参与者，如细胞死亡、细胞增殖和细胞代谢。此外，在模式生物中，目前已经证明FOXO功能会影响这些生物的寿命。多种信号转导途径调节FOXO功能，但最重要的是，它们受到蛋白激酶B（PKB/AKT）介导的磷酸化的负调控，因此构成胰岛素信号的重要下游成分。本期综述及时概述了我们对FOXO功能以及信号传导如何影响FOXO功能的理解。综合来看，关于FOXO功能和调控的综述研究提供了令人信服的证据，表明FOXO在衰老与包括糖尿病和癌症在内的年龄相关疾病之间的交叉点发挥作用。从这个角度来看，对FOXO功能和调控的进一步研究可能会揭示年龄如何影响疾病的发生和发展。
