Abstract
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.
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Acknowledgements
Work in my Laboratory is financially supported by the Dutch Cancer Foundation (KWF), Netherlands Organization of Science (NWO), Center of Biomedical Genetics (CBG) and Cancer Genomics Center (CGC). I thank all lab members past and present for their support and discussion, Tobias Dansen for critical reading of this manuscript and Cristina Arpesella for secretarial assistance in putting together this review issue.
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Burgering, B. A brief introduction to FOXOlogy. Oncogene 27, 2258–2262 (2008). https://doi.org/10.1038/onc.2008.29
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