Abstract
Proteins in the forkhead box O (FOXO) family contain three Akt phosphorylation sites that are important for export of the protein from the nucleus to the cytosol. In mammalian FOXO1, phosphorylation of serine 256 (S256) is a prerequisite for the phosphorylation of the other two sites. Although Drosophila FOXO (dFOXO) contains three well-conserved Akt phosphorylation sites, their role in the regulation of Drosophila physiology is not well understood. In the present study, we examine the regulation and function of phosphorylation at serine 190 (S190), which corresponds to S256 of mammalian FOXO1. Insulin and Akt were shown to increase S190 phosphorylation of dFOXO. Moreover, dFOXO nuclear export was induced by insulin treatment in both fly tissues and transfected Drosophila and human cells, and a protein containing an alanine substitution at S190 (dFOXOS190A) was defective in these insulin-dependent responses, suggesting that S190 phosphorylation is required for dFOXO nuclear export. Interestingly, dFOXOS190A and dFOXOS190D mutants showed lower target gene expression and a reduced ability to induce cell death compared to wild-type dFOXO. These results suggest that the S190 residue is required for dFOXO translocation and is important for the pro-apoptotic function of dFOXO.
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Abbreviations
- dFOXO:
-
Drosophila forkhead box O
- GMR:
-
Glass multimer reporter
- PI3K:
-
Phosphatidylinositol 3-kinase
- UAS:
-
Upstream activation sequence
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Acknowledgments
This work was supported by the Basic Science Research Program of the National Research Foundation of Korea funded by the Ministry of Education, Science, and Technology (2010-0023054, 2012-0006951, NRF-2012R1A1A2041611, and NRF-2013R1A1A2062046), by the Research Fund of Chungnam National University in 2010, and by the Korea Health Technology Research & Development Project, Ministry of Health & Welfare, Republic of Korea [A100876-1102-0000100 and HI12C1472 (A121587-1201-0000100)].
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All authors declared that there is no conflict of interest.
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Yoon Ki Hong and Dahye Lee have contributed equally to this work.
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Hong, Y.K., Lee, D., Hwang, S. et al. The role of serine 190 in FOXO nuclear export and cell death induction in Drosophila melanogaster . Genes Genom 36, 475–483 (2014). https://doi.org/10.1007/s13258-014-0182-0
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DOI: https://doi.org/10.1007/s13258-014-0182-0