Forkhead transcription factors have a ’winged helix’ domain and regulate processes that range from cell longevity to cell death.
Of the mammalian forkhead family members in the O class, FoxO1, FoxO3a and FoxO4 can fill a crucial void for the treatment of disorders that include aging, cancer, diabetes, infertility, neurodegeneration and immune system dysfunction.
Members of the class O of forkhead box transcription factors (FOXOs) have important roles in metabolism, cellular proliferation, stress tolerance and probably lifespan.
The activity of FOXOs is tightly regulated by post-translational modifications, including phosphorylation, acetylation and ubiquitylation.
Several of the enzymes that regulate the turnover of these post-translational modifications are shared between FoxO and p53.
These regulatory enzymes affect FoxO and p53 function in an opposite manner. This shared yet opposing regulatory network between FOXOs and p53 may underlie a ’trade-off’ between disease and lifespan.
Examples
FOXOA1
FOXO3A
References
van der Horst A, Burgering BM. Stressing the role of FoxO proteins in lifespan and disease. Nat Rev Mol Cell Biol. 2007 Jun;8(6):440-50. PMID: 17522590
Maiese K, Chong ZZ, Shang YC. OutFOXOing disease and disability: the therapeutic potential of targeting FoxO proteins. Trends Mol Med. 2008 May;14(5):219-227. PMID: 18403263
van der Horst A, Burgering BM. Stressing the role of FoxO proteins in lifespan and disease. Nat Rev Mol Cell Biol. 2007 Jun;8(6):440-50. PMID: 17522590
Barthel A, Schmoll D, Unterman TG. FoxO proteins in insulin action and metabolism. Trends Endocrinol Metab. 2005 May-Jun;16(4):183-9. PMID: 15860415