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KMID : 0381120140360040475
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Genes and Genomics
2014 Volume.36 No. 4 p.475 ~ p.483
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The role of serine 190 in FOXO nuclear export and cell death induction in Drosophila melanogaster
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Hong Yoon-Ki
Lee Da-Hye
Hwang Soo-Jin
Bang Se-Min
Jeong Hae-Min
Choi Seo-Yun
Phamd Tan-Viet
Kang Lin-Woo
Lee Young-Ha
Cho Kyoung-Sang
Cha Guang-Ho
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Abstract
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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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KEYWORD
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Akt, Apoptosis, dFOXO, Phosphorylation, Serine 190
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