The role of serine 190 in FOXO nuclear export and cell death induction in Drosophila melanogaster

详细信息    查看全文

• 作者：Yoon Ki Hong (1)
  Dahye Lee (2)
  Soojin Hwang (1)
  Se Min Bang (1)
  Haemin Jeong (1)
  Seoyun Choi (3)
  Tan-Viet Phamd (4)
  Lin-Woo Kang (1)
  Young-Ha Lee (2)
  Kyoung Sang Cho (1)
  Guang-Ho Cha (2)
  
• 关键词：Akt ; Apoptosis ; dFOXO ; Phosphorylation ; Serine 190
• 刊名：Genes & Genomics
• 出版年：2014
• 出版时间：August 2014
• 年：2014
• 卷：36
• 期：4
• 页码：475-483
• 全文大小：3,344 KB
• 参考文献：1. Arden KC (2008) FOXO animal models reveal a variety of diverse roles for FOXO transcription factors. Oncogene 27:2345鈥?350 CrossRef
  2. Bai H, Kang P, Tatar M (2012) Drosophila insulin-like peptide-6 (dilp6) expression from fat body extends lifespan and represses secretion of / Drosophila insulin-like peptide-2 from the brain. Aging Cell 11:978鈥?85 CrossRef
  3. Brent MM, Anand R, Marmorstein R (2008) Structural basis for DNA recognition by FoxO1 and its regulation by posttranslational modification. Structure聽16:1407鈥?416 CrossRef
  4. Brunet A, Bonni A, Zigmond MJ, Lin MZ, Juo P, Hu LS, Anderson MJ, Arden KC, Blenis J, Greenberg ME (1999) Akt promotes cell survival by phosphorylating and inhibiting a forkhead transcription factor. Cell 96:857鈥?68 CrossRef
  5. Calnan DR, Brunet A (2008) The FoxO code. Oncogene 27:2276鈥?288 CrossRef
  6. Carter ME, Brunet A (2007) FOXO transcription factors. Curr Biol 17:113鈥?14 CrossRef
  7. Cho KS, Lee JH, Kim S, Kim D, Koh H, Lee J, Kim C, Kim J, Chung J (2001) / Drosophila phosphoinositide-dependent kinase-1 regulates apoptosis and growth via the phosphoinositide 3-kinase-dependent signaling pathway. Proc Natl Acad Sci USA 98:6144鈥?149 CrossRef
  8. Henderson ST, Johnson TE (2001) daf-16 integrates developmental and environmental inputs to mediate aging in the nematode / Caenorhabditis elegans. Curr Biol 11:1975鈥?980 CrossRef
  9. Hong YK, Lee NG, Lee MJ, Park MS, Choi G, Suh YS, Han SY, Hwang S, Jeong G, Cho KS (2009) dXNP/DATRX increases apoptosis via the JNK and dFOXO pathway in / Drosophila neurons. Biochem Biophys Res Commun 384:160鈥?66 CrossRef
  10. Hong YK, Lee S, Park SH, Lee JH, Han SY, Kim ST, Kim YK, Jeon S, Koo BS, Cho KS (2012) Inhibition of JNK/dFOXO pathway and caspases rescues neurological impairments in / Drosophila Alzheimer鈥檚 disease model. Biochem Biophys Res Commun 419:49鈥?3 CrossRef
  11. Hwang S, Song S, Hong YK, Choi G, Suh YS, Han SY, Lee M, Park SH, Lee JH, Lee S et al (2013) Drosophila DJ-1 decreases neural sensitivity to stress by negatively regulating Daxx-like protein through dFOXO. PLoS Genet 9:e1003412 CrossRef
  12. J眉nger MA, Rintelen F, Stocker H, Wasserman JD, V茅gh M, Radimerski T, Greenberg ME, Hafen E (2003) The / Drosophila forkhead transcription factor FOXO mediates the reduction in cell number associated with reduced insulin signaling. J Biol 2:20 CrossRef
  13. Kanao T, Venderova K, Park DS, Unterman T, Lu B, Imai Y (2010) Activation of FoxO by LRRK2 induces expression of proapoptotic proteins and alters survival of postmitotic dopaminergic neuron in / Drosophila. Hum Mol Genet 19:3747鈥?758 CrossRef
  14. Koh H, Kim H, Kim MJ, Park J, Lee HJ, Chung J (2012) Silent information regulator 2 (Sir2) and forkhead box O (FOXO) complement mitochondrial dysfunction and dopaminergic neuron loss in / Drosophila Pten-induced kinase 1 (PINK1) null mutant. J Biol Chem 29:12750鈥?2758 CrossRef
  15. Kops GJ, de Ruiter ND, De Vries-Smits AM, Powell DR, Bos JL, Burgering BM (1999) Direct control of the forkhead transcription factor AFX by protein kinase B. Nature 398:630鈥?34 CrossRef
  16. Kramer JM, Davidge JT, Lockyer JM, Staveley BE (2003) Expression of / Drosophila FOXO regulates growth and can phenocopy starvation. BMC Dev Biol 5:3鈥?
  17. Lee JT, Ko K, Lee KJ, Lim MU, Moussavou G, Kim JS, Chang KT, Choo YK (2013) Effect of gangliosides on LPS stimulation and nitric oxide release in porcine kidney cell line PK15. Anim Cells Syst 17:341鈥?47 CrossRef
  18. Luo X, Puig O, Hyun J, Bohmann D, Jasper H (2007) Foxo and Fos regulate the decision between cell death and survival in response to UV irradiation. EMBO J 26:380鈥?90 CrossRef
  19. Nakae J, Barr V, Accili D (2000) Differential regulation of gene expression by insulin and IGF-1 receptors correlates with phosphorylation of a single amino acid residue in the forkhead transcription factor FKHR. EMBO J 19:989鈥?96 CrossRef
  20. Puig O, Mattila J (2011) Understanding forkhead box class O function: lessons from / Drosophila melanogaster. Antioxid Redox Signal 14:635鈥?47 CrossRef
  21. Puig O, Marr MT, Ruhf ML, Tjian R (2003) Control of cell number by / Drosophila FOXO: downstream and feedback regulation of the insulin receptor pathway. Genes Dev 17:2006鈥?020 CrossRef
  22. Rena G, Prescott AR, Guo S, Cohen P, Unterman TG (2001) Roles of the forkhead in rhabdomyosarcoma (FKHR) phosphorylation sites in regulating 14-3-3 binding, transactivation and nuclear targeting. Biochem J 354:605鈥?12 CrossRef
  23. Takaishi H, Konishi H, Matsuzaki H, Ono Y, Shirai Y, Saito N, Kitamura T, Ogawa W, Kasuga M, Kikkawa U et al (1999) Regulation of nuclear translocation of forkhead transcription factor AFX by protein kinase B. Proc Natl Acad Sci USA 96:11836鈥?1841 CrossRef
  24. Tang ED, Nu帽ez G, Barr FG, Guan KL (1999) Negative regulation of the forkhead transcription factor FKHR by Akt. J Biol Chem 274:16741鈥?6746 CrossRef
  25. van den Berg MC, Burgering BM (2011) Integrating opposing signals toward forkhead box O. Antioxid Redox Signal 14:607鈥?21 CrossRef
  26. Van Der Heide LP, Hoekman MF, Smidt MP (2004) The ins and outs of FoxO shuttling: mechanisms of FoxO translocation and transcriptional regulation. Biochem J 380:297鈥?09 CrossRef
  27. Verdu J, Buratovich MA, Wilder EL, Birnbaum MJ (1999) Cell-autonomous regulation of cell and organ growth in / Drosophila by Akt/PKB. Nat Cell Biol 1:500鈥?06 CrossRef
  28. Zhang X, Tang N, Hadden TJ, Rishi AK (2011) Akt, FoxO and regulation of apoptosis. Biochim Biophys Acta 1813:1978鈥?986 CrossRef
  
• 作者单位：Yoon Ki Hong (1)
  Dahye Lee (2)
  Soojin Hwang (1)
  Se Min Bang (1)
  Haemin Jeong (1)
  Seoyun Choi (3)
  Tan-Viet Phamd (4)
  Lin-Woo Kang (1)
  Young-Ha Lee (2)
  Kyoung Sang Cho (1)
  Guang-Ho Cha (2)
  
  1. Department of Biological Sciences, Konkuk University, Seoul, 143-701, Republic of Korea
  2. Department of Infection Biology, Chungnam National University, School of Medicine, Daejeon, 301-131, Republic of Korea
  3. The Ethel Walker School, Simsbury, CT, 06070, USA
  4. Department of Advanced Technology Fusion, Konkuk University, Seoul, 143-701, Republic of Korea
  
• ISSN：2092-9293

文摘

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.