Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Forkhead Box Protein O

  • Haitao Wang
  • Philip Lazarovici
  • Wenhua Zheng
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101601

Synonyms

 AF6q21;  AFX;  DAF-16;  dFoxO;  FKH1;  FKHR;  FKHRL1;  FKHRL1P2;  FoxO1;  FoxO1a;  FoxO3;  FoxO3a;  FoxO4;  FoxO6

Background

Forkhead box (Fox) proteins are a family of transcription factors that regulate the transcription of genes regulating diverse cellular processes, including cell survival, apoptosis, oxidative stress response and redox signaling, proliferation, differentiation, metabolism, and life span. Fox proteins are classified into subclasses FoxA–FoxS, and subgroup O (FoxO) proteins are a subgroup of the Fox family, which is characterized by a conserved DNA-binding domain (the “Forkhead box,” or Fox). This domain could recognize the specific DNA sequence localized in the promoter and thus regulate the transcription/expression of these genes. Forkhead gene (fkh) was cloned for the first time from the fly Drosophila melanogasterand has been identified to play important roles during the developing process of the anterior and posterior gut of the embryo. Genetic...

This is a preview of subscription content, log in to check access.

Notes

Acknowledgments

This research was financially supported by the Guangdong Provincial Project of Science and Technology (2011B050200005), the National Natural Science Foundation of China (31371088), SRG2015-00004-FHS and MYRG2016-00052-FHS from University of Macau, and the Science and Technology Development Fund (FDCT) of Macao (FDCT 021/2015/A1).

References

  1. Bahia PK, Pugh V, Hoyland K, Hensley V, Rattray M, Williams RJ. Neuroprotective effects of phenolic antioxidant tBHQ associate with inhibition of FoxO3a nuclear translocation and activity. J Neurochem. 2012;123(1):182–91.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Battiprolu PK, Hojayev B, Jiang N, Wang ZV, Luo X, Iglewski M, et al. Metabolic stress-induced activation of FoxO1 triggers diabetic cardiomyopathy in mice. J Clin Invest. 2012;122(3):1109–18.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Boura E, Rezabkova L, Brynda J, Obsilova V, Obsil T. Structure of the human FOXO4-DBD-DNA complex at 1.9 A resolution reveals new details of FOXO binding to the DNA. Acta Crystallogr D Biol Crystallogr. 2010;66(Pt 12):1351–7.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Brunet A, Bonni A, Zigmond MJ, Lin MZ, Juo P, Hu LS, et al. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell. 1999;96(6):857–68.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Brunet A, Kanai F, Stehn J, Xu J, Sarbassova D, Frangioni JV, et al. 14-3-3 transits to the nucleus and participates in dynamic nucleocytoplasmic transport. J Cell Biol. 2002;156(5):817–28.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Brunet A, Sweeney LB, Sturgill JF, Chua KF, Greer PL, Lin Y, et al. Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science. 2004;303(5666):2011–5.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Bullock M. FOXO factors and breast cancer: outfoxing endocrine resistance. Endocr Relat Cancer. 2016;23(2):R113–30.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Buteau J, Spatz ML, Accili D. Transcription factor FoxO1 mediates glucagon-like peptide-1 effects on pancreatic beta-cell mass. Diabetes. 2006;55(5):1190–6.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Calnan DR, Webb AE, White JL, Stowe TR, Goswami T, Shi X, et al. Methylation by Set9 modulates FoxO3 stability and transcriptional activity. Aging (Albany NY). 2012;4(7):462–79.CrossRefGoogle Scholar
  10. Carter ME, Brunet A. FOXO transcription factors. Curr Biol. 2007;17(4):R113–4.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Chong ZZ, Li F, Maiese K. Group I metabotropic receptor neuroprotection requires Akt and its substrates that govern FOXO3a, Bim, and beta-catenin during oxidative stress. Curr Neurovasc Res. 2006;3(2):107–17.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Clark KL, Halay ED, Lai E, Burley SK. Co-crystal structure of the HNF-3/fork head DNA-recognition motif resembles histone H5. Nature. 1993;364(6436):412–20.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Cornforth AN, Davis JS, Khanifar E, Nastiuk KL, Krolewski JJ. FOXO3a mediates the androgen-dependent regulation of FLIP and contributes to TRAIL-induced apoptosis of LNCaP cells. Oncogene. 2008;27(32):4422–33.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Daitoku H, Hatta M, Matsuzaki H, Aratani S, Ohshima T, Miyagishi M, et al. Silent information regulator 2 potentiates Foxo1-mediated transcription through its deacetylase activity. Proc Natl Acad Sci USA. 2004;101(27):10042–7.PubMedPubMedCentralCrossRefGoogle Scholar
  15. de la Torre-Ubieta L, Gaudilliere B, Yang Y, Ikeuchi Y, Yamada T, DiBacco S, et al. A FOXO-Pak1 transcriptional pathway controls neuronal polarity. Genes Dev. 2010;24(8):799–813.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Dijkers PF, Birkenkamp KU, Lam EW, Thomas NS, Lammers JW, Koenderman L, et al. FKHR-L1 can act as a critical effector of cell death induced by cytokine withdrawal: protein kinase B-enhanced cell survival through maintenance of mitochondrial integrity. J Cell Biol. 2002;156(3):531–42.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Dillin A, Crawford DK, Kenyon C. Timing requirements for insulin/IGF-1 signaling in C. elegans. Science. 2002;298(5594):830–4.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Estevez AO, Morgan KL, Szewczyk NJ, Gems D, Estevez M. The neurodegenerative effects of selenium are inhibited by FOXO and PINK1/PTEN regulation of insulin/insulin-like growth factor signaling in Caenorhabditis elegans. Neurotoxicology. 2014;41:28–43.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Fluteau A, Ince PG, Minett T, Matthews FE, Brayne C, Garwood CJ, et al. The nuclear retention of transcription factor FOXO3a correlates with a DNA damage response and increased glutamine synthetase expression by astrocytes suggesting a neuroprotective role in the ageing brain. Neurosci Lett. 2015;609:11–7.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Fu Z, Tindall DJ. FOXOs, cancer and regulation of apoptosis. Oncogene. 2008;27(16):2312–9.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Furuyama T, Nakazawa T, Nakano I, Mori N. Identification of the differential distribution patterns of mRNAs and consensus binding sequences for mouse DAF-16 homologues. Biochem J. 2000;349(Pt 2):629–34.PubMedPubMedCentralCrossRefGoogle Scholar
  22. Galili N, Davis RJ, Fredericks WJ, Mukhopadhyay S, Rauscher 3rd FJ, Emanuel BS, et al. Fusion of a fork head domain gene to PAX3 in the solid tumour alveolar rhabdomyosarcoma. Nat Genet. 1993;5(3):230–5.PubMedPubMedCentralCrossRefGoogle Scholar
  23. Giannakou ME, Partridge L. The interaction between FOXO and SIRT1: tipping the balance towards survival. Trends Cell Biol. 2004;14(8):408–12.PubMedPubMedCentralCrossRefGoogle Scholar
  24. Gilels F, Paquette ST, Zhang J, Rahman I, White PM. Mutation of Foxo3 causes adult onset auditory neuropathy and alters cochlear synapse architecture in mice. J Neurosci. 2013;33(47):18409–24.PubMedPubMedCentralCrossRefGoogle Scholar
  25. Gopinath SD, Webb AE, Brunet A, Rando TA. FOXO3 promotes quiescence in adult muscle stem cells during the process of self-renewal. Stem Cell Reports. 2014;2(4):414–26.PubMedPubMedCentralCrossRefGoogle Scholar
  26. Greer EL, Brunet A. FOXO transcription factors at the interface between longevity and tumor suppression. Oncogene. 2005;24(50):7410–25.PubMedPubMedCentralCrossRefGoogle Scholar
  27. Greer EL, Oskoui PR, Banko MR, Maniar JM, Gygi MP, Gygi SP, et al. The energy sensor AMP-activated protein kinase directly regulates the mammalian FOXO3 transcription factor. J Biol Chem. 2007;282(41):30107–19.PubMedPubMedCentralCrossRefGoogle Scholar
  28. Gustafson D, Rothenberg E, Blennow K, Steen B, Skoog I. An 18-year follow-up of overweight and risk of Alzheimer disease. Arch Intern Med. 2003;163(13):1524–8.PubMedPubMedCentralCrossRefGoogle Scholar
  29. Hedrick SM, Hess Michelini R, Doedens AL, Goldrath AW, Stone EL. FOXO transcription factors throughout T cell biology. Nat Rev Immunol. 2012;12(9):649–61.PubMedPubMedCentralCrossRefGoogle Scholar
  30. Hillion J, Le Coniat M, Jonveaux P, Berger R, Bernard OA. AF6q21, a novel partner of the MLL gene in t(6;11)(q21;q23), defines a forkhead transcriptional factor subfamily. Blood. 1997;90(9):3714–9.PubMedPubMedCentralGoogle Scholar
  31. Hoekman MF, Jacobs FM, Smidt MP, Burbach JP. Spatial and temporal expression of FoxO transcription factors in the developing and adult murine brain. Gene Expr Patterns. 2006;6(2):134–40.PubMedPubMedCentralCrossRefGoogle Scholar
  32. Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev. 2007;87(4):1409–39.PubMedPubMedCentralCrossRefGoogle Scholar
  33. Holzenberger M, Dupont J, Ducos B, Leneuve P, Geloen A, Even PC, et al. IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature. 2003;421(6919):182–7.PubMedPubMedCentralCrossRefGoogle Scholar
  34. Hong YK, Lee S, Park SH, Lee JH, Han SY, Kim ST, et al. Inhibition of JNK/dFOXO pathway and caspases rescues neurological impairments in Drosophila Alzheimer’s disease model. Biochem Biophys Res Commun. 2012;419(1):49–53.PubMedPubMedCentralCrossRefGoogle Scholar
  35. Hosaka T, Biggs 3rd WH, Tieu D, Boyer AD, Varki NM, Cavenee WK, et al. Disruption of forkhead transcription factor (FOXO) family members in mice reveals their functional diversification. Proc Natl Acad Sci USA. 2004;101(9):2975–80.PubMedPubMedCentralCrossRefGoogle Scholar
  36. Hou J, Chong ZZ, Shang YC, Maiese K. FOXO3a governs early and late apoptotic endothelial programs during elevated glucose through mitochondrial and caspase signaling. Mol Cell Endocrinol. 2010;321(2):194–206.PubMedPubMedCentralCrossRefGoogle Scholar
  37. Hyun SW, Jung YS. Hypoxia induces FoxO3a-mediated dysfunction of blood-brain barrier. Biochem Biophys Res Commun. 2014;450(4):1638–42.PubMedPubMedCentralCrossRefGoogle Scholar
  38. Jackson JG, Kreisberg JI, Koterba AP, Yee D, Brattain MG. Phosphorylation and nuclear exclusion of the forkhead transcription factor FKHR after epidermal growth factor treatment in human breast cancer cells. Oncogene. 2000;19(40):4574–81.PubMedPubMedCentralCrossRefGoogle Scholar
  39. Kaestner KH, Knochel W, Martinez DE. Unified nomenclature for the winged helix/forkhead transcription factors. Genes Dev. 2000;14(2):142–6.PubMedPubMedCentralGoogle Scholar
  40. Katoh M, Katoh M. Human FOX gene family (Review). Int J Oncol. 2004;25(5):1495–500.PubMedPubMedCentralGoogle Scholar
  41. Kim JJ, Li P, Huntley J, Chang JP, Arden KC, Olefsky JM. FoxO1 haploinsufficiency protects against high-fat diet-induced insulin resistance with enhanced peroxisome proliferator-activated receptor gamma activation in adipose tissue. Diabetes. 2009;58(6):1275–82.PubMedPubMedCentralCrossRefGoogle Scholar
  42. Kim DH, Perdomo G, Zhang T, Slusher S, Lee S, Phillips BE, et al. FoxO6 integrates insulin signaling with gluconeogenesis in the liver. Diabetes. 2011;60(11):2763–74.PubMedPubMedCentralCrossRefGoogle Scholar
  43. Kress TR, Cannell IG, Brenkman AB, Samans B, Gaestel M, Roepman P, et al. The MK5/PRAK kinase and Myc form a negative feedback loop that is disrupted during colorectal tumorigenesis. Mol Cell. 2011;41(4):445–57.PubMedPubMedCentralCrossRefGoogle Scholar
  44. Kwon ES, Narasimhan SD, Yen K, Tissenbaum HA. A new DAF-16 isoform regulates longevity. Nature. 2010;466(7305):498–502.PubMedPubMedCentralCrossRefGoogle Scholar
  45. Lai E, Prezioso VR, Smith E, Litvin O, Costa RH, Darnell Jr JE. HNF-3A, a hepatocyte-enriched transcription factor of novel structure is regulated transcriptionally. Genes Dev. 1990;4(8):1427–36.PubMedPubMedCentralCrossRefGoogle Scholar
  46. Lee SJ, Seo BR, Choi EJ, Koh JY. The role of reciprocal activation of cAbl and Mst1 in the oxidative death of cultured astrocytes. Glia. 2014;62(4):639–48.PubMedPubMedCentralCrossRefGoogle Scholar
  47. Lehtinen MK, Yuan Z, Boag PR, Yang Y, Villen J, Becker EB, et al. A conserved MST-FOXO signaling pathway mediates oxidative-stress responses and extends life span. Cell. 2006;125(5):987–1001.PubMedPubMedCentralCrossRefGoogle Scholar
  48. Li H, Liang J, Castrillon DH, DePinho RA, Olson EN, Liu ZP. FoxO4 regulates tumor necrosis factor alpha-directed smooth muscle cell migration by activating matrix metalloproteinase 9 gene transcription. Mol Cell Biol. 2007a;27(7):2676–86.PubMedPubMedCentralCrossRefGoogle Scholar
  49. Li HH, Willis MS, Lockyer P, Miller N, McDonough H, Glass DJ, et al. Atrogin-1 inhibits Akt-dependent cardiac hypertrophy in mice via ubiquitin-dependent coactivation of Forkhead proteins. J Clin Invest. 2007b;117(11):3211–23.PubMedPubMedCentralCrossRefGoogle Scholar
  50. Li X, Zhang T, Wilson A, Amarachintha S, Sertorio M, Pang Q. Transcriptional profiling of Foxo3a and Fancd2 regulated genes in mouse hematopoietic stem cells. Genom Data. 2015;4:148–9.PubMedPubMedCentralCrossRefGoogle Scholar
  51. Lin K, Dorman JB, Rodan A, Kenyon C. daf-16: An HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans. Science. 1997;278(5341):1319–22.PubMedPubMedCentralCrossRefGoogle Scholar
  52. Luo CT, Liao W, Dadi S, Toure A, Li MO. Graded Foxo1 activity in Treg cells differentiates tumour immunity from spontaneous autoimmunity. Nature. 2016;529(7587):532–6.PubMedPubMedCentralCrossRefGoogle Scholar
  53. Maiese K. FoxO proteins in the nervous system. Anal Cell Pathol (Amst). 2015;2015:569392.Google Scholar
  54. Maiese K. Forkhead transcription factors: new considerations for alzheimer’s disease and dementia. J Trans Sci. 2016;2(4):241–7.CrossRefGoogle Scholar
  55. Maiese K, Chong ZZ, Shang YC, Hou J. Rogue proliferation versus restorative protection: where do we draw the line for Wnt and forkhead signaling? Expert Opin Ther Targets. 2008;12(7):905–16.PubMedPubMedCentralCrossRefGoogle Scholar
  56. Maiese K, Chong ZZ, Hou J, Shang YC. The “O” class: crafting clinical care with FoxO transcription factors. Adv Exp Med Biol. 2009a;665:242–60.PubMedPubMedCentralCrossRefGoogle Scholar
  57. Maiese K, Hou J, Chong ZZ, Shang YC. A fork in the path: developing therapeutic inroads with FoxO proteins. Oxidative Med Cell Longev. 2009b;2(3):119–29.CrossRefGoogle Scholar
  58. Mao Z, Liu L, Zhang R, Li X. Lithium reduces FoxO3a transcriptional activity by decreasing its intracellular content. Biol Psychiatry. 2007;62(12):1423–30.PubMedPubMedCentralCrossRefGoogle Scholar
  59. Martins R, Lithgow GJ, Link W. Long live FOXO: unraveling the role of FOXO proteins in aging and longevity. Aging Cell. 2016;15(2):196–207.PubMedPubMedCentralCrossRefGoogle Scholar
  60. Matsuzaki H, Daitoku H, Hatta M, Aoyama H, Yoshimochi K, Fukamizu A. Acetylation of Foxo1 alters its DNA-binding ability and sensitivity to phosphorylation. Proc Natl Acad Sci USA. 2005;102(32):11278–83.PubMedPubMedCentralCrossRefGoogle Scholar
  61. McKinnon CM, Ravier MA, Rutter GA. FoxO1 is required for the regulation of preproglucagon gene expression by insulin in pancreatic alphaTC1-9 cells. J Biol Chem. 2006;281(51):39358–69.PubMedPubMedCentralCrossRefGoogle Scholar
  62. Merkely B, Gara E, Lendvai Z, Skopal J, Leja T, Zhou W, et al. Signaling via PI3K/FOXO1A pathway modulates formation and survival of human embryonic stem cell-derived endothelial cells. Stem Cells Dev. 2015;24(7):869–78.PubMedPubMedCentralCrossRefGoogle Scholar
  63. Miyamoto K, Araki KY, Naka K, Arai F, Takubo K, Yamazaki S, et al. Foxo3a is essential for maintenance of the hematopoietic stem cell pool. Cell Stem Cell. 2007;1(1):101–12.PubMedPubMedCentralCrossRefGoogle Scholar
  64. Modur V, Nagarajan R, Evers BM, Milbrandt J. FOXO proteins regulate tumor necrosis factor-related apoptosis inducing ligand expression. Implications for PTEN mutation in prostate cancer. J Biol Chem. 2002;277(49):47928–37.PubMedPubMedCentralCrossRefGoogle Scholar
  65. Moll L, Schubert M. The role of insulin and insulin-like growth factor-1/FoxO-mediated transcription for the pathogenesis of obesity-associated dementia. Curr Gerontol Geriatr Res. 2012;2012:384094.PubMedPubMedCentralCrossRefGoogle Scholar
  66. Monsalve M, Olmos Y. The complex biology of FOXO. Curr Drug Targets. 2011;12(9):1322–50.PubMedPubMedCentralCrossRefGoogle Scholar
  67. Murakami S. Stress resistance in long-lived mouse models. Exp Gerontol. 2006;41(10):1014–9.PubMedPubMedCentralCrossRefGoogle Scholar
  68. Naka K, Hoshii T, Muraguchi T, Tadokoro Y, Ooshio T, Kondo Y, et al. TGF-beta-FOXO signalling maintains leukaemia-initiating cells in chronic myeloid leukaemia. Nature. 2010;463(7281):676–80.PubMedPubMedCentralCrossRefGoogle Scholar
  69. Nakae J, Kitamura T, Silver DL, Accili D. The forkhead transcription factor Foxo1 (Fkhr) confers insulin sensitivity onto glucose-6-phosphatase expression. J Clin Invest. 2001;108(9):1359–67.PubMedPubMedCentralCrossRefGoogle Scholar
  70. Nho RS, Hergert P. FoxO3a and disease progression. World J Biol Chem. 2014;5(3):346–54.PubMedPubMedCentralCrossRefGoogle Scholar
  71. Obsil T, Obsilova V. Structure/function relationships underlying regulation of FOXO transcription factors. Oncogene. 2008;27(16):2263–75.PubMedPubMedCentralCrossRefGoogle Scholar
  72. Obsil T, Obsilova V. Structural basis for DNA recognition by FOXO proteins. Biochim Biophys Acta. 2011;1813(11):1946–53.PubMedPubMedCentralCrossRefGoogle Scholar
  73. Pajvani UB, Shawber CJ, Samuel VT, Birkenfeld AL, Shulman GI, Kitajewski J, et al. Inhibition of Notch signaling ameliorates insulin resistance in a FoxO1-dependent manner. Nat Med. 2011;17(8):961–7.PubMedPubMedCentralCrossRefGoogle Scholar
  74. Peng S, Zhao S, Yan F, Cheng J, Huang L, Chen H, et al. HDAC2 selectively regulates FOXO3a-mediated gene transcription during oxidative stress-induced neuronal cell death. J Neurosci. 2015;35(3):1250–9.PubMedPubMedCentralCrossRefGoogle Scholar
  75. Perrot V, Rechler MM. The coactivator p300 directly acetylates the forkhead transcription factor Foxo1 and stimulates Foxo1-induced transcription. Mol Endocrinol. 2005;19(9):2283–98.PubMedPubMedCentralCrossRefGoogle Scholar
  76. Pino E, Amamoto R, Zheng L, Cacquevel M, Sarria JC, Knott GW, et al. FOXO3 determines the accumulation of alpha-synuclein and controls the fate of dopaminergic neurons in the substantia nigra. Hum Mol Genet. 2014;23(6):1435–52.PubMedPubMedCentralCrossRefGoogle Scholar
  77. Potter CJ, Pedraza LG, Huang H, Xu T. The tuberous sclerosis complex (TSC) pathway and mechanism of size control. Biochem Soc Trans. 2003;31(Pt 3):584–6.PubMedPubMedCentralCrossRefGoogle Scholar
  78. Putker M, Vos HR, van Dorenmalen K, de Ruiter H, Duran AG, Snel B, et al. Evolutionary acquisition of cysteines determines FOXO paralog-specific redox signaling. Antioxid Redox Signal. 2015;22(1):15–28.PubMedPubMedCentralCrossRefGoogle Scholar
  79. Reagan-Shaw S, Ahmad N. The role of Forkhead-box Class O (FoxO) transcription factors in cancer: a target for the management of cancer. Toxicol Appl Pharmacol. 2007;224(3):360–8.PubMedPubMedCentralCrossRefGoogle Scholar
  80. Rector RS, Morris EM, Ridenhour S, Meers GM, Hsu FF, Turk J, et al. Selective hepatic insulin resistance in a murine model heterozygous for a mitochondrial trifunctional protein defect. Hepatology. 2013;57(6):2213–23.PubMedPubMedCentralCrossRefGoogle Scholar
  81. Ren H, Orozco IJ, Su Y, Suyama S, Gutierrez-Juarez R, Horvath TL, et al. FoxO1 target Gpr17 activates AgRP neurons to regulate food intake. Cell. 2012;149(6):1314–26.PubMedPubMedCentralCrossRefGoogle Scholar
  82. Renault VM, Rafalski VA, Morgan AA, Salih DA, Brett JO, Webb AE, et al. FoxO3 regulates neural stem cell homeostasis. Cell Stem Cell. 2009;5(5):527–39.PubMedPubMedCentralCrossRefGoogle Scholar
  83. Salih DA, Rashid AJ, Colas D, de la Torre-Ubieta L, Zhu RP, Morgan AA, et al. FoxO6 regulates memory consolidation and synaptic function. Genes Dev. 2012;26(24):2780–801.PubMedPubMedCentralCrossRefGoogle Scholar
  84. Scodelaro Bilbao P, Boland R. Extracellular ATP regulates FoxO family of transcription factors and cell cycle progression through PI3K/Akt in MCF-7 cells. Biochim Biophys Acta. 2013;1830(10):4456–69.PubMedPubMedCentralCrossRefGoogle Scholar
  85. Shang YC, Chong ZZ, Hou J, Maiese K. Wnt1, FoxO3a, and NF-kappaB oversee microglial integrity and activation during oxidant stress. Cell Signal. 2010;22(9):1317–29.PubMedPubMedCentralCrossRefGoogle Scholar
  86. Shiota M, Yokomizo A, Kashiwagi E, Tada Y, Inokuchi J, Tatsugami K, et al. Foxo3a expression and acetylation regulate cancer cell growth and sensitivity to cisplatin. Cancer Sci. 2010;101(5):1177–85.PubMedPubMedCentralCrossRefGoogle Scholar
  87. Soriano FX, Papadia S, Hofmann F, Hardingham NR, Bading H, Hardingham GE. Preconditioning doses of NMDA promote neuroprotection by enhancing neuronal excitability. J Neurosci. 2006;26(17):4509–18.PubMedPubMedCentralCrossRefGoogle Scholar
  88. Stitt TN, Drujan D, Clarke BA, Panaro F, Timofeyva Y, Kline WO, et al. The IGF-1/PI3K/Akt pathway prevents expression of muscle atrophy-induced ubiquitin ligases by inhibiting FOXO transcription factors. Mol Cell. 2004;14(3):395–403.PubMedPubMedCentralCrossRefGoogle Scholar
  89. Su SH, Wang YQ, Wu YF, Wang DP, Lin Q, Hai J. Cannabinoid receptor agonist WIN55,212-2 and fatty acid amide hydrolase inhibitor URB597 may protect against cognitive impairment in rats of chronic cerebral hypoperfusion via PI3K/AKT signaling. Behav Brain Res. 2016;313:334–44.PubMedPubMedCentralCrossRefGoogle Scholar
  90. Sunters A, Fernandez de Mattos S, Stahl M, Brosens JJ, Zoumpoulidou G, Saunders CA, et al. FoxO3a transcriptional regulation of Bim controls apoptosis in paclitaxel-treated breast cancer cell lines. J Biol Chem. 2003;278(50):49795–805.PubMedPubMedCentralCrossRefGoogle Scholar
  91. Trinh DL, Scott DW, Morin RD, Mendez-Lago M, An J, Jones SJ, et al. Analysis of FOXO1 mutations in diffuse large B-cell lymphoma. Blood. 2013;121(18):3666–74.PubMedPubMedCentralCrossRefGoogle Scholar
  92. Tsai KL, Sun YJ, Huang CY, Yang JY, Hung MC, Hsiao CD. Crystal structure of the human FOXO3a-DBD/DNA complex suggests the effects of post-translational modification. Nucleic Acids Res. 2007;35(20):6984–94.PubMedPubMedCentralCrossRefGoogle Scholar
  93. Tullet JM, Hertweck M, An JH, Baker J, Hwang JY, Liu S, et al. Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans. Cell. 2008;132(6):1025–38.PubMedPubMedCentralCrossRefGoogle Scholar
  94. Tzivion G, Dobson M, Ramakrishnan G. FoxO transcription factors; regulation by AKT and 14-3-3 proteins. Biochim Biophys Acta. 2011;1813(11):1938–45.PubMedPubMedCentralCrossRefGoogle Scholar
  95. Uranga RM, Katz S, Salvador GA. Enhanced phosphatidylinositol 3-kinase (PI3K)/Akt signaling has pleiotropic targets in hippocampal neurons exposed to iron-induced oxidative stress. J Biol Chem. 2013;288(27):19773–84.PubMedPubMedCentralCrossRefGoogle Scholar
  96. Urbanek P, Klotz LO. Posttranscriptional regulation of FOXO expression: microRNAs and beyond. Br J Pharmacol. 2016. doi: 10.1111/bph.13471.CrossRefPubMedPubMedCentralGoogle Scholar
  97. van der Horst A, Burgering BM. Stressing the role of FoxO proteins in lifespan and disease. Nat Rev Mol Cell Biol. 2007;8(6):440–50.PubMedPubMedCentralCrossRefGoogle Scholar
  98. van der Horst A, de Vries-Smits AM, Brenkman AB, van Triest MH, van den Broek N, Colland F, et al. FOXO4 transcriptional activity is regulated by monoubiquitination and USP7/HAUSP. Nat Cell Biol. 2006;8(10):1064–73.PubMedPubMedCentralCrossRefGoogle Scholar
  99. Vidal RL, Figueroa A, Court FA, Thielen P, Molina C, Wirth C, et al. Targeting the UPR transcription factor XBP1 protects against Huntington’s disease through the regulation of FoxO1 and autophagy. Hum Mol Genet. 2012;21(10):2245–62.PubMedPubMedCentralCrossRefGoogle Scholar
  100. Vogt PK, Jiang H, Aoki M. Triple layer control: phosphorylation, acetylation and ubiquitination of FOXO proteins. Cell Cycle. 2005;4(7):908–13.PubMedPubMedCentralCrossRefGoogle Scholar
  101. Wang F, Nguyen M, Qin FX, Tong Q. SIRT2 deacetylates FOXO3a in response to oxidative stress and caloric restriction. Aging Cell. 2007;6(4):505–14.PubMedPubMedCentralCrossRefGoogle Scholar
  102. Wang F, Marshall CB, Yamamoto K, Li GY, Plevin MJ, You H, et al. Biochemical and structural characterization of an intramolecular interaction in FOXO3a and its binding with p53. J Mol Biol. 2008;384(3):590–603.PubMedPubMedCentralCrossRefGoogle Scholar
  103. Wang F, Chan CH, Chen K, Guan X, Lin HK, Tong Q. Deacetylation of FOXO3 by SIRT1 or SIRT2 leads to Skp2-mediated FOXO3 ubiquitination and degradation. Oncogene. 2012a;31(12):1546–57.PubMedPubMedCentralCrossRefGoogle Scholar
  104. Wang H, Zhang Q, Wen Q, Zheng Y, Lazarovici P, Jiang H, et al. Proline-rich Akt substrate of 40 kDa (PRAS40): a novel downstream target of PI3k/Akt signaling pathway. Cell Signal. 2012b;24(1):17–24.PubMedPubMedCentralCrossRefGoogle Scholar
  105. Wang H, Duan X, Ren Y, Liu Y, Huang M, Liu P, et al. FoxO3a negatively regulates nerve growth factor-induced neuronal differentiation through inhibiting the expression of neurochondrin in PC12 cells. Mol Neurobiol. 2013a;47(1):24–36.PubMedPubMedCentralCrossRefGoogle Scholar
  106. Wang H, Zhou X, Huang J, Mu N, Guo Z, Wen Q, et al. The role of Akt/FoxO3a in the protective effect of venlafaxine against corticosterone-induced cell death in PC12 cells. Psychopharmacology. 2013b;228(1):129–41.PubMedPubMedCentralCrossRefGoogle Scholar
  107. Wang S, Chong ZZ, Shang YC, Maiese K. WISP1 neuroprotection requires FoxO3a post-translational modulation with autoregulatory control of SIRT1. Curr Neurovasc Res. 2013c;10(1):54–69.PubMedPubMedCentralCrossRefGoogle Scholar
  108. Wang Y, Zhou Y, Graves DT. FOXO transcription factors: their clinical significance and regulation. Biomed Res Int. 2014;2014:925350.PubMedPubMedCentralGoogle Scholar
  109. Wang H, Quirion R, Little PJ, Cheng Y, Feng ZP, Sun HS, et al. Forkhead box O transcription factors as possible mediators in the development of major depression. Neuropharmacology. 2015;99:527–37.PubMedPubMedCentralCrossRefGoogle Scholar
  110. Warr MR, Binnewies M, Flach J, Reynaud D, Garg T, Malhotra R, et al. FOXO3A directs a protective autophagy program in haematopoietic stem cells. Nature. 2013;494(7437):323–7.PubMedPubMedCentralCrossRefGoogle Scholar
  111. Watroba M, Maslinska D, Maslinski S. Current overview of functions of FoxO proteins, with special regards to cellular homeostasis, cell response to stress, as well as inflammation and aging. Adv Med Sci. 2012;57(2):183–95.PubMedPubMedCentralCrossRefGoogle Scholar
  112. Weigel D, Jackle H. The fork head domain: a novel DNA binding motif of eukaryotic transcription factors? Cell. 1990;63(3):455–6.PubMedPubMedCentralCrossRefGoogle Scholar
  113. Weigel D, Jurgens G, Kuttner F, Seifert E, Jackle H. The homeotic gene fork head encodes a nuclear protein and is expressed in the terminal regions of the Drosophila embryo. Cell. 1989;57(4):645–58.PubMedPubMedCentralCrossRefGoogle Scholar
  114. Wen Q, Duan X, Liao R, Little P, Gao G, Jiang H, et al. Characterization of intracellular translocation of Forkhead transcription factor O (FoxO) members induced by NGF in PC12 cells. Neurosci Lett. 2011;498(1):31–6.PubMedPubMedCentralCrossRefGoogle Scholar
  115. Wen Q, Wang H, Little PJ, Quirion R, Zheng W. Forkhead family transcription factor FoxO and neural differentiation. Neurogenetics. 2012;13(2):105–13.PubMedPubMedCentralCrossRefGoogle Scholar
  116. Wilk A, Urbanska K, Yang S, Wang JY, Amini S, Del Valle L, et al. Insulin-like growth factor-I-forkhead box O transcription factor 3a counteracts high glucose/tumor necrosis factor-alpha-mediated neuronal damage: implications for human immunodeficiency virus encephalitis. J Neurosci Res. 2011;89(2):183–98.PubMedPubMedCentralCrossRefGoogle Scholar
  117. Xiong X, Xie R, Zhang H, Gu L, Xie W, Cheng M, et al. PRAS40 plays a pivotal role in protecting against stroke by linking the Akt and mTOR pathways. Neurobiol Dis. 2014;66:43–52.PubMedPubMedCentralCrossRefGoogle Scholar
  118. Xu G, Liu J, Yoshimoto K, Chen G, Iwata T, Mizusawa N, et al. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces expression of p27(kip(1)) and FoxO3a in female rat cerebral cortex and PC12 cells. Toxicol Lett. 2014;226(3):294–302.PubMedPubMedCentralCrossRefGoogle Scholar
  119. Yang M, Pi H, Li M, Xu S, Zhang L, Xie J, et al. Autophagy induction contributes to cadmium toxicity in mesenchymal stem cells via AMPK/FOXO3a/BECN1 signaling. Toxicol Sci. 2016;154(1):101–14.Google Scholar
  120. Yoo KY, Kwon SH, Lee CH, Yan B, Park JH, Ahn JH, et al. FoxO3a changes in pyramidal neurons and expresses in non-pyramidal neurons and astrocytes in the gerbil hippocampal CA1 region after transient cerebral ischemia. Neurochem Res. 2012;37(3):588–95.PubMedPubMedCentralCrossRefGoogle Scholar
  121. Zeldich E, Chen CD, Colvin TA, Bove-Fenderson EA, Liang J, Tucker Zhou TB, et al. The neuroprotective effect of Klotho is mediated via regulation of members of the redox system. J Biol Chem. 2014;289(35):24700–15.PubMedPubMedCentralCrossRefGoogle Scholar
  122. Zeng Z, Wang H, Shang F, Zhou L, Little PJ, Quirion R, et al. Lithium ions attenuate serum-deprivation-induced apoptosis in PC12 cells through regulation of the Akt/FoxO1 signaling pathways. Psychopharmacology. 2016;233(5):785–94.PubMedPubMedCentralCrossRefGoogle Scholar
  123. Zhang W, Konopleva M, Burks JK, Dywer KC, Schober WD, Yang JY, et al. Blockade of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase and murine double minute synergistically induces Apoptosis in acute myeloid leukemia via BH3-only proteins Puma and Bim. Cancer Res. 2010;70(6):2424–34.PubMedPubMedCentralCrossRefGoogle Scholar
  124. Zhang X, Yalcin S, Lee DF, Yeh TY, Lee SM, Su J, et al. FOXO1 is an essential regulator of pluripotency in human embryonic stem cells. Nat Cell Biol. 2011;13(9):1092–9.PubMedPubMedCentralCrossRefGoogle Scholar
  125. Zhang L, Tschumi BO, Lopez-Mejia IC, Oberle SG, Meyer M, Samson G, et al. Mammalian target of rapamycin complex 2 controls CD8 T cell memory differentiation in a Foxo1-dependent manner. Cell Rep. 2016;14(5):1206–17.PubMedPubMedCentralCrossRefGoogle Scholar
  126. Zhao Y, Wang Y, Zhu WG. Applications of post-translational modifications of FoxO family proteins in biological functions. J Mol Cell Biol. 2011;3(5):276–82.PubMedPubMedCentralCrossRefGoogle Scholar
  127. Zheng WH, Quirion R. Comparative signaling pathways of insulin-like growth factor-1 and brain-derived neurotrophic factor in hippocampal neurons and the role of the PI3 kinase pathway in cell survival. J Neurochem. 2004;89(4):844–52.PubMedPubMedCentralCrossRefGoogle Scholar
  128. Zheng WH, Quirion R. Insulin-like growth factor-1 (IGF-1) induces the activation/phosphorylation of Akt kinase and cAMP response element-binding protein (CREB) by activating different signaling pathways in PC12 cells. BMC Neurosci. 2006;7:51.PubMedPubMedCentralCrossRefGoogle Scholar
  129. Zheng WH, Quirion R. Glutamate acting on N-methyl-D-aspartate receptors attenuates insulin-like growth factor-1 receptor tyrosine phosphorylation and its survival signaling properties in rat hippocampal neurons. J Biol Chem. 2009;284(2):855–61.PubMedPubMedCentralCrossRefGoogle Scholar
  130. Zheng WH, Kar S, Quirion R. FKHRL1 and its homologs are new targets of nerve growth factor Trk receptor signaling. J Neurochem. 2002a;80(6):1049–61.PubMedPubMedCentralCrossRefGoogle Scholar
  131. Zheng WH, Kar S, Quirion R. Insulin-like growth factor-1-induced phosphorylation of transcription factor FKHRL1 is mediated by phosphatidylinositol 3-kinase/Akt kinase and role of this pathway in insulin-like growth factor-1-induced survival of cultured hippocampal neurons. Mol Pharmacol. 2002b;62(2):225–33.PubMedPubMedCentralCrossRefGoogle Scholar
  132. Zhou W, Cao Q, Peng Y, Zhang QJ, Castrillon DH, DePinho RA, et al. FoxO4 inhibits NF-kappaB and protects mice against colonic injury and inflammation. Gastroenterology. 2009;137(4):1403–14.PubMedPubMedCentralCrossRefGoogle Scholar
  133. Zhu WL, Tong H, Teh JT, Wang M. Forkhead box protein O3 transcription factor negatively regulates autophagy in human cancer cells by inhibiting forkhead box protein O1 expression and cytosolic accumulation. PLoS One. 2014;9(12):e115087.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Faculty of Health SciencesUniversity of MacauTaipa, MacauChina
  2. 2.School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhouChina
  3. 3.School of Pharmacy Institute for Drug Research, Faculty of MedicineThe Hebrew University of JerusalemJerusalemIsrael