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Structure/function relationships underlying regulation of FOXO transcription factors

Abstract

The FOXO subgroup of forkhead transcription factors plays a central role in cell-cycle control, differentiation, metabolism control, stress response and apoptosis. Therefore, the function of these important molecules is tightly controlled by a wide range of protein–protein interactions and posttranslational modifications including phosphorylation, acetylation and ubiquitination. The mechanisms by which these processes regulate FOXO activity are mostly elusive. This review focuses on recent advances in structural studies of forkhead transcription factors and the insights they provide into the mechanism of DNA recognition. On the basis of these data, we discuss structural aspects of protein–protein interactions and posttranslational modifications that target the forkhead domain and the nuclear localization signal of FOXO proteins.

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Acknowledgements

We thank Professor CD Hsiao for providing us with coordinates of the FOXO3a DBD−DNA complex structure. We also thank the members of our lab for helpful comments on the manuscript. The authors are supported by grants from the Grant Agency of the Czech Republic (204/06/0565), the Grant Agency of the Academy of Sciences of the Czech Republic (KJB500110601), the Ministry of Education, Youth, and Sports of the Czech Republic (MSM0021620857, LC554) and the Academy of Sciences of the Czech Republic (AV0Z50110509).

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Obsil, T., Obsilova, V. Structure/function relationships underlying regulation of FOXO transcription factors. Oncogene 27, 2263–2275 (2008). https://doi.org/10.1038/onc.2008.20

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