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Nat Rev Mol Cell Biol. 2013 Feb;14(2):83-97. doi: 10.1038/nrm3507. Epub 2013 Jan 17.

FOXOs: signalling integrators for homeostasis maintenance.

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Molecular Cancer Research, Division Biomedical Genetics, University Medical Center Utrecht, Stratenum, Universiteitsweg 100, 3584CG Utrecht, The Netherlands.


Forkhead box O (FOXO) transcription factors are involved in the regulation of the cell cycle, apoptosis and metabolism. In model organisms, FOXO activity also affects stem cell maintenance and lifespan as well as age-related diseases, such as cancer and diabetes. Multiple upstream pathways regulate FOXO activity through post-translational modifications and nuclear-cytoplasmic shuttling of both FOXO and its regulators. The diversity of this upstream regulation and the downstream effects of FOXOs suggest that they function as homeostasis regulators to maintain tissue homeostasis over time and coordinate a response to environmental changes, including growth factor deprivation, metabolic stress (starvation) and oxidative stress.

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