Foxo1

Summary

Gene Symbol: Foxo1
Description: forkhead box O1
Alias: AI876417, Afxh, FKHR, Fkhr1, Foxo1a, forkhead box protein O1, forkhead box O1a, forkhead box protein O1A, forkhead in rhabdomyosarcoma, forkhead protein 1
Species: mouse
Products:     Foxo1

Top Publications

  1. Richards J, Sharma S, Falender A, Lo Y. Expression of FKHR, FKHRL1, and AFX genes in the rodent ovary: evidence for regulation by IGF-I, estrogen, and the gonadotropins. Mol Endocrinol. 2002;16:580-99 pubmed
    ..mouse and rat models, we show 1) that FKHR [Forkhead homolog of rhabdomysarcoma = Forkhead box binding protein (Foxo1), FKHRL1 (Forkhead-like protein-1 = Foxo3), and AFX (a Forkhead transcription factor = Foxo4); all defined ..
  2. Altomonte J, Richter A, Harbaran S, Suriawinata J, Nakae J, Thung S, et al. Inhibition of Foxo1 function is associated with improved fasting glycemia in diabetic mice. Am J Physiol Endocrinol Metab. 2003;285:E718-28 pubmed
    ..The forkhead transcription factor Foxo1 has been implicated as a mediator of insulin action in regulating hepatic gluconeogenesis, and a Foxo1 mutant (..
  3. Mihaylova M, Vasquez D, Ravnskjaer K, Denechaud P, Yu R, Alvarez J, et al. Class IIa histone deacetylases are hormone-activated regulators of FOXO and mammalian glucose homeostasis. Cell. 2011;145:607-21 pubmed publisher
    ..Finally, suppression of class IIa HDACs in mouse models of type 2 diabetes ameliorates hyperglycemia, suggesting that inhibitors of class I/II HDACs may be potential therapeutics for metabolic syndrome. ..
  4. Teixeira C, Liu Y, Thant L, Pang J, Palmer G, Alikhani M. Foxo1, a novel regulator of osteoblast differentiation and skeletogenesis. J Biol Chem. 2010;285:31055-65 pubmed publisher
    ..The pathways that control mesenchymal cell differentiation are not well understood. We propose that Foxo1 is an early molecular regulator during mesenchymal cell differentiation into osteoblasts...
  5. Iskandar K, Cao Y, Hayashi Y, Nakata M, Takano E, Yada T, et al. PDK-1/FoxO1 pathway in POMC neurons regulates Pomc expression and food intake. Am J Physiol Endocrinol Metab. 2010;298:E787-98 pubmed publisher
    ..Forkhead box-containing protein-O1 (FoxO1) is inactivated in a PI(3)K-dependent manner...
  6. Nakae J, Cao Y, Oki M, Orba Y, Sawa H, Kiyonari H, et al. Forkhead transcription factor FoxO1 in adipose tissue regulates energy storage and expenditure. Diabetes. 2008;57:563-76 pubmed
    ..However, physiological roles of FoxO1 in adipose tissue remain unclear...
  7. Alkhatib A, Werner M, Hug E, Herzog S, Eschbach C, Faraidun H, et al. FoxO1 induces Ikaros splicing to promote immunoglobulin gene recombination. J Exp Med. 2012;209:395-406 pubmed publisher
    ..Further analysis revealed that the transcription factor FoxO1 is crucial for Ikaros expression and that PI3K-mediated down-regulation of FoxO1 suppresses Ikaros expression...
  8. Goertz M, Wu Z, Gallardo T, Hamra F, Castrillon D. Foxo1 is required in mouse spermatogonial stem cells for their maintenance and the initiation of spermatogenesis. J Clin Invest. 2011;121:3456-66 pubmed publisher
    ..Here, we investigated a role for the Foxo transcription factors in mouse spermatogenesis and found that Foxo1 specifically marks mouse gonocytes and a subset of spermatogonia with stem cell potential...
  9. Manning B, Logsdon M, Lipovsky A, Abbott D, Kwiatkowski D, Cantley L. Feedback inhibition of Akt signaling limits the growth of tumors lacking Tsc2. Genes Dev. 2005;19:1773-8 pubmed
    ..This study demonstrates that attenuation of the PI3K-Akt pathway in tumors lacking TSC2 contributes to their benign nature. ..

More Information

Publications92

  1. McKinnon C, Ravier M, Rutter G. FoxO1 is required for the regulation of preproglucagon gene expression by insulin in pancreatic alphaTC1-9 cells. J Biol Chem. 2006;281:39358-69 pubmed
    Forkhead/winged helix box gene, group O-1 (FoxO1) is a member of a family of nuclear transcription factors regulated by insulin-dependent phosphorylation and implicated in the development of the endocrine pancreas...
  2. Ochiai K, Maienschein Cline M, Mandal M, Triggs J, Bertolino E, Sciammas R, et al. A self-reinforcing regulatory network triggered by limiting IL-7 activates pre-BCR signaling and differentiation. Nat Immunol. 2012;13:300-7 pubmed publisher
    ..Attenuation of IL-7 signaling resulted in upregulation of the transcription factors Foxo1 and Pax5, which coactivated many pre-B cell genes, including Rag1, Rag2 and Blnk...
  3. Yuan Z, Becker E, Merlo P, Yamada T, Dibacco S, Konishi Y, et al. Activation of FOXO1 by Cdk1 in cycling cells and postmitotic neurons. Science. 2008;319:1665-8 pubmed publisher
    ..We found that Cdk1 phosphorylated the transcription factor FOXO1 at Ser249 in vitro and in vivo...
  4. Skarra D, Arriola D, Benson C, Thackray V. Forkhead box O1 is a repressor of basal and GnRH-induced Fshb transcription in gonadotropes. Mol Endocrinol. 2013;27:1825-39 pubmed publisher
    ..Recently, we reported that insulin regulates FOXO1 phosphorylation and cellular localization in pituitary gonadotropes and that FOXO1 overexpression inhibits Lhb ..
  5. Liu Z, Castrillon D, Zhou W, Richards J. FOXO1/3 depletion in granulosa cells alters follicle growth, death and regulation of pituitary FSH. Mol Endocrinol. 2013;27:238-52 pubmed publisher
    The Forkhead boxO (FOXO) transcription factors regulate multiple cellular functions. FOXO1 and FOXO3 are highly expressed in granulosa cells of ovarian follicles...
  6. Hariharan N, Maejima Y, Nakae J, Paik J, Depinho R, Sadoshima J. Deacetylation of FoxO by Sirt1 Plays an Essential Role in Mediating Starvation-Induced Autophagy in Cardiac Myocytes. Circ Res. 2010;107:1470-82 pubmed publisher
    ..by increased mRFP-GFP-LC3 puncta and decreases in p62, which was accompanied by upregulation of Sirt1 and FoxO1. Overexpression of either Sirt1 or FoxO1 was sufficient for inducing autophagic flux, whereas both Sirt1 and FoxO1 ..
  7. Cheng Z, Guo S, Copps K, Dong X, Kollipara R, Rodgers J, et al. Foxo1 integrates insulin signaling with mitochondrial function in the liver. Nat Med. 2009;15:1307-11 pubmed publisher
    ..The expression of several forkhead box O1 (Foxo1) target genes increased in the DKO liver, including heme oxygenase-1 (Hmox1), which disrupts complex III and IV of ..
  8. Ren H, Orozco I, Su Y, Suyama S, Gutierrez Juarez R, Horvath T, et al. FoxO1 target Gpr17 activates AgRP neurons to regulate food intake. Cell. 2012;149:1314-26 pubmed publisher
    ..b>FoxO1 is a shared mediator of both pathways, and its inhibition is required to induce satiety...
  9. Rao R, Li Q, Gubbels Bupp M, Shrikant P. Transcription factor Foxo1 represses T-bet-mediated effector functions and promotes memory CD8(+) T cell differentiation. Immunity. 2012;36:374-87 pubmed publisher
    ..Although, Foxo1 is known to be important in regulating CD8(+) T cell trafficking and homeostasis, its role in functional ..
  10. Matsumoto M, Han S, Kitamura T, Accili D. Dual role of transcription factor FoxO1 in controlling hepatic insulin sensitivity and lipid metabolism. J Clin Invest. 2006;116:2464-72 pubmed
    ..Here we show that adenoviral delivery of constitutively nuclear forkhead box O1 (FoxO1) to mouse liver results in steatosis arising from increased triglyceride accumulation and decreased fatty acid ..
  11. Liu H, Fergusson M, Wu J, Rovira I, Liu J, Gavrilova O, et al. Wnt signaling regulates hepatic metabolism. Sci Signal. 2011;4:ra6 pubmed publisher
    ..Furthermore, ?-catenin interacted with the transcription factor FoxO1 in livers from mice under starved conditions...
  12. Cao Y, Kamioka Y, Yokoi N, Kobayashi T, Hino O, Onodera M, et al. Interaction of FoxO1 and TSC2 induces insulin resistance through activation of the mammalian target of rapamycin/p70 S6K pathway. J Biol Chem. 2006;281:40242-51 pubmed
    Both TSC2 (tuberin) and forkhead transcription factor FoxO1 are phosphorylated and inhibited by Akt and play important roles in insulin signaling. However, little is known about the relationship between TSC2 and FoxO1...
  13. Gonzalez E, Flier E, Molle D, Accili D, McGraw T. Hyperinsulinemia leads to uncoupled insulin regulation of the GLUT4 glucose transporter and the FoxO1 transcription factor. Proc Natl Acad Sci U S A. 2011;108:10162-7 pubmed publisher
    ..which translocation of the GLUT4 glucose transporter to the cell surface is blunted yet nuclear exclusion of the FoxO1 transcription factor is preserved, rendering uncoupled insulin-controlled carbohydrate and lipid metabolisms...
  14. Amin R, Schlissel M. Foxo1 directly regulates the transcription of recombination-activating genes during B cell development. Nat Immunol. 2008;9:613-22 pubmed publisher
    ..of the genes encoding RAG-1 and RAG-2 in transformed pro-B cells by a pathway requiring the transcription factor Foxo1. Foxo1 directly activated transcription of the Rag1-Rag2 locus throughout early B cell development, and a decrease ..
  15. Fan W, Imamura T, Sonoda N, SEARS D, Patsouris D, Kim J, et al. FOXO1 transrepresses peroxisome proliferator-activated receptor gamma transactivation, coordinating an insulin-induced feed-forward response in adipocytes. J Biol Chem. 2009;284:12188-97 pubmed publisher
    The transcriptional factor FoxO1 plays an important role in metabolic homeostasis...
  16. Yusuf I, Zhu X, Kharas M, Chen J, Fruman D. Optimal B-cell proliferation requires phosphoinositide 3-kinase-dependent inactivation of FOXO transcription factors. Blood. 2004;104:784-7 pubmed
    ..Here, we show that B-cell receptor (BCR) engagement triggers PI3K-dependent phosphorylation and nuclear export of FOXO1. Furthermore, forced expression of PI3K-independent variants of FOXO1 or FOXO3a in activated B cells induces ..
  17. Wei D, Tao R, Zhang Y, White M, Dong X. Feedback regulation of hepatic gluconeogenesis through modulation of SHP/Nr0b2 gene expression by Sirt1 and FoxO1. Am J Physiol Endocrinol Metab. 2011;300:E312-20 pubmed publisher
    ..gene), an orphan nuclear receptor, which has been shown to suppress the activity of forkhead transcription factor FoxO1, was decreased in the liver of LKO(Sirt)¹ mice...
  18. Paik J, Kollipara R, Chu G, Ji H, Xiao Y, Ding Z, et al. FoxOs are lineage-restricted redundant tumor suppressors and regulate endothelial cell homeostasis. Cell. 2007;128:309-23 pubmed
    ..The highly related members of the mammalian FoxO transcription factor family, FoxO1, FoxO3, and FoxO4, represent one of several effector arms of PI3K-AKT signaling, prompting genetic analysis of the ..
  19. Jacobs F, van der Heide L, Wijchers P, Burbach J, Hoekman M, Smidt M. FoxO6, a novel member of the FoxO class of transcription factors with distinct shuttling dynamics. J Biol Chem. 2003;278:35959-67 pubmed
    ..localization after stimulation with growth factors, in contrast to the predominant cytosolic localization of FoxO1 and FoxO3...
  20. Puigserver P, Rhee J, Donovan J, Walkey C, Yoon J, Oriente F, et al. Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-1alpha interaction. Nature. 2003;423:550-5 pubmed
    ..Two components known to have important physiological roles in this process are the forkhead transcription factor FOXO1 (also known as FKHR) and peroxisome proliferative activated receptor-gamma co-activator 1 (PGC-1alpha; also known ..
  21. Shen M, Lin F, Zhang J, Tang Y, Chen W, Liu H. Involvement of the up-regulated FoxO1 expression in follicular granulosa cell apoptosis induced by oxidative stress. J Biol Chem. 2012;287:25727-40 pubmed publisher
    ..In this study, the involvement of FoxO1 in oxidative stress-induced apoptosis of mouse follicular granulosa cells (MGCs) was investigated in vivo and in ..
  22. Kitamura T, Nakae J, Kitamura Y, Kido Y, Biggs W, Wright C, et al. The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic beta cell growth. J Clin Invest. 2002;110:1839-47 pubmed
    ..We report that haploinsufficiency for the forkhead transcription factor Foxo1 reverses beta cell failure in Irs2(-/-) mice through partial restoration of beta cell proliferation and increased ..
  23. Kerdiles Y, Stone E, Beisner D, Beisner D, McGargill M, Ch en I, et al. Foxo transcription factors control regulatory T cell development and function. Immunity. 2010;33:890-904 pubmed publisher
    ..Here, we showed the absence of Foxo1 severely curtailed the development of Foxp3(+) regulatory T (Treg) cells and those that developed were ..
  24. Naimi M, Gautier N, Chaussade C, Valverde A, Accili D, Van Obberghen E. Nuclear forkhead box O1 controls and integrates key signaling pathways in hepatocytes. Endocrinology. 2007;148:2424-34 pubmed
    ..After being phosphorylated by protein kinase B (PKB) on S253 in its DNA-binding domain, Foxo1 is phosphorylated on T24 and additional sites, which overall triggers its nuclear exclusion...
  25. Tao R, Wei D, Gao H, Liu Y, Depinho R, Dong X. Hepatic FoxOs regulate lipid metabolism via modulation of expression of the nicotinamide phosphoribosyltransferase gene. J Biol Chem. 2011;286:14681-90 pubmed publisher
    ..we examined the phenotypic consequences of liver-specific deletion of three members of the FoxO family: FoxO1, FoxO3, and FoxO4...
  26. Kim H, Kobayashi M, Sasaki T, Kikuchi O, Amano K, Kitazumi T, et al. Overexpression of FoxO1 in the hypothalamus and pancreas causes obesity and glucose intolerance. Endocrinology. 2012;153:659-71 pubmed publisher
    ..of insulin signaling, plays important roles in ?-cells and the hypothalamus when we investigated the roles of FoxO1 independently in the pancreas and hypothalamus...
  27. Kim M, Pak Y, Jang P, Namkoong C, Choi Y, Won J, et al. Role of hypothalamic Foxo1 in the regulation of food intake and energy homeostasis. Nat Neurosci. 2006;9:901-6 pubmed
    ..Studies suggest that the forkhead transcription factor Foxo1 is an important mediator of insulin signaling in peripheral tissues...
  28. Sekine K, Chen Y, Kojima N, Ogata K, Fukamizu A, Miyajima A. Foxo1 links insulin signaling to C/EBPalpha and regulates gluconeogenesis during liver development. EMBO J. 2007;26:3607-15 pubmed
    ..We show here that expression of Foxo1 was sharply increased in the perinatal liver and augmented C/EBPalpha-dependent transcription...
  29. Zhang W, Patil S, Chauhan B, Guo S, Powell D, Le J, et al. FoxO1 regulates multiple metabolic pathways in the liver: effects on gluconeogenic, glycolytic, and lipogenic gene expression. J Biol Chem. 2006;281:10105-17 pubmed
    ..understand the role of FoxO proteins in the liver, we created transgenic mice expressing constitutively active FoxO1 in the liver using the alpha1-antitrypsin promoter...
  30. Marshall A, van der Ent M, Grosveld G. PAX3-FOXO1 and FGFR4 in alveolar rhabdomyosarcoma. Mol Carcinog. 2012;51:807-15 pubmed publisher
    ..FGFR4 as a direct transcriptional target of the alveolar rhabdomyosarcoma (ARMS) specific fusion protein, PAX3-FOXO1. We hypothesized fibroblast growth factor receptor 4 (FGFR4) may act as an effector of PAX3-FOXO1, contributing to ..
  31. Ambrogini E, Almeida M, Martin Millan M, Paik J, Depinho R, Han L, et al. FoxO-mediated defense against oxidative stress in osteoblasts is indispensable for skeletal homeostasis in mice. Cell Metab. 2010;11:136-46 pubmed publisher
    ..Conditional deletion of FoxO1, FoxO3, and FoxO4 in 3-month-old mice resulted in an increase in oxidative stress in bone and osteoblast apoptosis ..
  32. 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 U S A. 2004;101:10042-7 pubmed
    ..Here we show that reversible acetylation of Foxo1 (also known as FKHR), the mouse DAF-16 ortholog, modulates its transactivation function...
  33. Kerdiles Y, Beisner D, Tinoco R, Dejean A, Castrillon D, Depinho R, et al. Foxo1 links homing and survival of naive T cells by regulating L-selectin, CCR7 and interleukin 7 receptor. Nat Immunol. 2009;10:176-84 pubmed publisher
    ..Here we show that Foxo1 has a crucial, nonredundant role in T cells...
  34. Nakae J, Kitamura T, Silver D, Accili D. The forkhead transcription factor Foxo1 (Fkhr) confers insulin sensitivity onto glucose-6-phosphatase expression. J Clin Invest. 2001;108:1359-67 pubmed
    ..The inability to respond to insulin is associated with reduced expression of the forkhead transcription factor Foxo1, a substrate of the Akt kinase that is inhibited by insulin through phosphorylation...
  35. Asada S, Daitoku H, Matsuzaki H, Saito T, Sudo T, Mukai H, et al. Mitogen-activated protein kinases, Erk and p38, phosphorylate and regulate Foxo1. Cell Signal. 2007;19:519-27 pubmed
    ..b>Foxo1 (FKHR) contains 15 consensus phosphorylation sites for the mitogen-activated protein kinase (MAPK) family...
  36. Nakae J, Cao Y, Daitoku H, Fukamizu A, Ogawa W, Yano Y, et al. The LXXLL motif of murine forkhead transcription factor FoxO1 mediates Sirt1-dependent transcriptional activity. J Clin Invest. 2006;116:2473-83 pubmed
    The forkhead transcription factor FoxO1 has been identified as a negative regulator of insulin/IGF-1 signaling. Its function is inhibited by phosphorylation and nuclear exclusion through a PI3K-dependent pathway...
  37. Huang H, Regan K, Lou Z, Chen J, Tindall D. CDK2-dependent phosphorylation of FOXO1 as an apoptotic response to DNA damage. Science. 2006;314:294-7 pubmed
    ..CDK2 specifically phosphorylated FOXO1 at serine-249 (Ser249) in vitro and in vivo...
  38. Ouyang W, Liao W, Luo C, Yin N, Huse M, Kim M, et al. Novel Foxo1-dependent transcriptional programs control T(reg) cell function. Nature. 2012;491:554-9 pubmed publisher
    ..Here we show that Foxo1 is a pivotal regulator of T(reg )cell function...
  39. Jing E, Gesta S, Kahn C. SIRT2 regulates adipocyte differentiation through FoxO1 acetylation/deacetylation. Cell Metab. 2007;6:105-14 pubmed
    ..The mechanism underlying the effects of reduced SIRT2 in 3T3-L1 adipocytes includes increased acetylation of FOXO1, with direct interaction between SIRT2 and FOXO1...
  40. Kim K, Donato J, Berglund E, Choi Y, Kohno D, Elias C, et al. FOXO1 in the ventromedial hypothalamus regulates energy balance. J Clin Invest. 2012;122:2578-89 pubmed publisher
    The transcription factor FOXO1 plays a central role in metabolic homeostasis by regulating leptin and insulin activity in many cell types, including neurons...
  41. Di Pietro N, Panel V, Hayes S, Bagattin A, Meruvu S, Pandolfi A, et al. Serum- and glucocorticoid-inducible kinase 1 (SGK1) regulates adipocyte differentiation via forkhead box O1. Mol Endocrinol. 2010;24:370-80 pubmed publisher
    ..We demonstrate that SGK1 affects differentiation by direct phosphorylation of Foxo1, thereby changing its cellular localization from the nucleus to the cytosol...
  42. Ni Y, Berenji K, Wang N, Oh M, Sachan N, Dey A, et al. Foxo transcription factors blunt cardiac hypertrophy by inhibiting calcineurin signaling. Circulation. 2006;114:1159-68 pubmed
    ..However, downstream molecular events are not yet well defined. Here, we report that expression of either Foxo1 or Foxo3 in cardiomyocytes attenuates calcineurin phosphatase activity and inhibits agonist-induced hypertrophic ..
  43. Haeusler R, Kaestner K, Accili D. FoxOs function synergistically to promote glucose production. J Biol Chem. 2010;285:35245-8 pubmed publisher
    ..production (HGP) plays a vital role in maintaining the supply of glucose to the body, and transcription factor FoxO1 is known to confer hormone responsiveness onto HGP...
  44. Kitamura Y, Kitamura T, Kruse J, Raum J, Stein R, Gu W, et al. FoxO1 protects against pancreatic beta cell failure through NeuroD and MafA induction. Cell Metab. 2005;2:153-63 pubmed
    ..quot; We show that the forkhead protein FoxO1 protects beta cells against oxidative stress by forming a complex with the promyelocytic leukemia protein Pml and ..
  45. Matsumoto M, Pocai A, Rossetti L, Depinho R, Accili D. Impaired regulation of hepatic glucose production in mice lacking the forkhead transcription factor Foxo1 in liver. Cell Metab. 2007;6:208-16 pubmed
    ..We show that inactivation of the gene encoding forkhead protein Foxo1 in mouse liver results in 40% reduction of glucose levels at birth and 30% reduction in adult mice after a 48 hr ..
  46. Nakae J, Biggs W, Kitamura T, Cavenee W, Wright C, Arden K, et al. Regulation of insulin action and pancreatic beta-cell function by mutated alleles of the gene encoding forkhead transcription factor Foxo1. Nat Genet. 2002;32:245-53 pubmed
    ..It is not known whether the two defects share a common pathogenesis. We show that haploinsufficiency of the Foxo1 gene, encoding a forkhead transcription factor (forkhead box transcription factor O1), restores insulin ..
  47. Moylan J, Smith J, Chambers M, McLoughlin T, Reid M. TNF induction of atrogin-1/MAFbx mRNA depends on Foxo4 expression but not AKT-Foxo1/3 signaling. Am J Physiol Cell Physiol. 2008;295:C986-93 pubmed publisher
    ..The mechanism involves release of inhibition of Forkhead transcription factors, namely Foxo1 and Foxo3...
  48. Yan L, Lavin V, Moser L, Cui Q, Kanies C, Yang E. PP2A regulates the pro-apoptotic activity of FOXO1. J Biol Chem. 2008;283:7411-20 pubmed publisher
    b>FOXO1, a member of the evolutionarily conserved forkhead family of transcription factors, regulates expression of a number of genes that play critical roles in cell cycle and apoptosis...
  49. Plum L, Lin H, Dutia R, Tanaka J, Aizawa K, Matsumoto M, et al. The obesity susceptibility gene Cpe links FoxO1 signaling in hypothalamic pro-opiomelanocortin neurons with regulation of food intake. Nat Med. 2009;15:1195-201 pubmed publisher
    ..food intake through actions in the central nervous system that are partly mediated by the transcription factor FoxO1. We show that FoxO1 ablation in pro-opiomelanocortin (Pomc)-expressing neurons in mice (here called Pomc-Foxo1(-/-)..
  50. Wolfrum C, Asilmaz E, Luca E, Friedman J, Stoffel M. Foxa2 regulates lipid metabolism and ketogenesis in the liver during fasting and in diabetes. Nature. 2004;432:1027-32 pubmed
    ..Pharmacological intervention to inhibit phosphorylation of Foxa2 may be an effective treatment for type 2 diabetes. ..
  51. Hosaka T, Biggs W, Tieu D, Boyer A, Varki N, Cavenee W, et al. Disruption of forkhead transcription factor (FOXO) family members in mice reveals their functional diversification. Proc Natl Acad Sci U S A. 2004;101:2975-80 pubmed
    ..The mammalian orthologs of DAF-16, the closely-related FOXO subclass of forkhead transcription factors (FKHR/FOXO1, FKHRL1/FOXO3a, and AFX/FOXO4), also have important roles in cell cycle arrest, apoptosis and stress responses in ..
  52. Belgardt B, Husch A, Rother E, Ernst M, Wunderlich F, Hampel B, et al. PDK1 deficiency in POMC-expressing cells reveals FOXO1-dependent and -independent pathways in control of energy homeostasis and stress response. Cell Metab. 2008;7:291-301 pubmed publisher
    ..Expression of a dominant-negative mutant of FOXO1 specifically in POMC cells is sufficient to ameliorate positive energy balance in PDK1(DeltaPOMC) mice but cannot ..
  53. Tothova Z, Kollipara R, Huntly B, Lee B, Castrillon D, Cullen D, et al. FoxOs are critical mediators of hematopoietic stem cell resistance to physiologic oxidative stress. Cell. 2007;128:325-39 pubmed
    To understand the role of FoxO family members in hematopoiesis, we conditionally deleted FoxO1, FoxO3, and FoxO4 in the adult hematopoietic system...
  54. Schulz D, Vassen L, Chow K, McWhirter S, Amin R, Moroy T, et al. Gfi1b negatively regulates Rag expression directly and via the repression of FoxO1. J Exp Med. 2012;209:187-99 pubmed publisher
    ..changes in the Rag locus, whereas indirect inhibition is achieved through repression of the trans-activator Foxo1. Together, our experiments show that Gfi family members are essential for normal B cell development and play an ..
  55. Zhang K, Li L, Qi Y, Zhu X, Gan B, Depinho R, et al. Hepatic suppression of Foxo1 and Foxo3 causes hypoglycemia and hyperlipidemia in mice. Endocrinology. 2012;153:631-46 pubmed publisher
    ..In this study, we used the Cre/LoxP genetic approach to delete the Foxo1, Foxo3, and Foxo4 genes individually or a combination of two or all in the liver of lean or db/db mice and ..
  56. Dengler H, Baracho G, Omori S, Bruckner S, Arden K, Castrillon D, et al. Distinct functions for the transcription factor Foxo1 at various stages of B cell differentiation. Nat Immunol. 2008;9:1388-98 pubmed publisher
    The transcription factors Foxo1, Foxo3 and Foxo4 modulate cell fate 'decisions' in diverse systems. Here we show that Foxo1-dependent gene expression was critical at many stages of B cell differentiation...
  57. Martinez S, Cras Méneur C, Bernal Mizrachi E, Permutt M. Glucose regulates Foxo1 through insulin receptor signaling in the pancreatic islet beta-cell. Diabetes. 2006;55:1581-91 pubmed
    ..In this study, we tested the hypothesis that glucose regulates Foxo1 activity in the beta-cell via an autocrine/paracrine effect of released insulin on its receptor...
  58. Samuel V, Choi C, Phillips T, Romanelli A, Geisler J, Bhanot S, et al. Targeting foxo1 in mice using antisense oligonucleotide improves hepatic and peripheral insulin action. Diabetes. 2006;55:2042-50 pubmed
    ..The transcription factor Foxo1 links insulin signaling to decreased transcription of PEPCK and glucose-6-phosphatase (G6Pase) and provides a ..
  59. Kamei Y, Miura S, Suzuki M, Kai Y, Mizukami J, Taniguchi T, et al. Skeletal muscle FOXO1 (FKHR) transgenic mice have less skeletal muscle mass, down-regulated Type I (slow twitch/red muscle) fiber genes, and impaired glycemic control. J Biol Chem. 2004;279:41114-23 pubmed
    b>FOXO1, a member of the FOXO forkhead type transcription factors, is markedly up-regulated in skeletal muscle in energy-deprived states such as fasting and severe diabetes, but its functions in skeletal muscle have remained poorly ..
  60. Hinman R, Bushanam J, Nichols W, Satterthwaite A. B cell receptor signaling down-regulates forkhead box transcription factor class O 1 mRNA expression via phosphatidylinositol 3-kinase and Bruton's tyrosine kinase. J Immunol. 2007;178:740-7 pubmed
    ..down-regulation of proapoptotic and antimitogenic genes such as forkhead box transcription factor class O 1 (FOXO1) is an important component of this process...
  61. Haeusler R, Han S, Accili D. Hepatic FoxO1 ablation exacerbates lipid abnormalities during hyperglycemia. J Biol Chem. 2010;285:26861-8 pubmed publisher
    ..Transcription factor FoxO1 is regulated dually by insulin and nutrients...
  62. Stitt T, Drujan D, Clarke B, Panaro F, Timofeyva Y, Kline W, et al. The IGF-1/PI3K/Akt pathway prevents expression of muscle atrophy-induced ubiquitin ligases by inhibiting FOXO transcription factors. Mol Cell. 2004;14:395-403 pubmed
    ..for this inhibition involves Akt-mediated inhibition of the FoxO family of transcription factors; a mutant form of FOXO1, which prevents Akt phosphorylation, thereby prevents Akt-mediated inhibition of MuRF1 and MAFbx upregulation...
  63. Lazorchak A, Liu D, Facchinetti V, Di Lorenzo A, Sessa W, Schatz D, et al. Sin1-mTORC2 suppresses rag and il7r gene expression through Akt2 in B cells. Mol Cell. 2010;39:433-43 pubmed publisher
    ..mediates the Sin1-mTORC2 dependent suppression of il7r and rag gene expression in B cells by regulating FoxO1 phosphorylation...
  64. Nakae J, Oki M, Cao Y. The FoxO transcription factors and metabolic regulation. FEBS Lett. 2008;582:54-67 pubmed
    ..The understanding of molecular mechanism how FoxOs affect glucose or lipid metabolism will shed light on the novel therapy of type 2 diabetes and the metabolic syndrome. ..
  65. Fu W, Ma Q, Chen L, Li P, Zhang M, Ramamoorthy S, et al. MDM2 acts downstream of p53 as an E3 ligase to promote FOXO ubiquitination and degradation. J Biol Chem. 2009;284:13987-4000 pubmed publisher
    ..We show that MDM2 binds to FOXO1 and FOXO3A and promotes their ubiquitination and degradation, a process apparently dependent on FOXO ..
  66. Qiao L, Shao J. SIRT1 regulates adiponectin gene expression through Foxo1-C/enhancer-binding protein alpha transcriptional complex. J Biol Chem. 2006;281:39915-24 pubmed
    ..Recent studies have indicated that forkhead transcription factor O1 (Foxo1) and silent information regulator 2 mammalian ortholog SIRT1 are involved in adipogenesis...
  67. Wu Z, Jiao P, Huang X, Feng B, Feng Y, Yang S, et al. MAPK phosphatase-3 promotes hepatic gluconeogenesis through dephosphorylation of forkhead box O1 in mice. J Clin Invest. 2010;120:3901-11 pubmed publisher
    ..In vitro experiments identified forkhead box O1 (FOXO1) as a substrate for MKP-3...
  68. Xu P, Das M, Reilly J, Davis R. JNK regulates FoxO-dependent autophagy in neurons. Genes Dev. 2011;25:310-22 pubmed publisher
    ..These data identify JNK as a potent negative regulator of FoxO-dependent autophagy in neurons. ..
  69. Senokuchi T, Liang C, Seimon T, Han S, Matsumoto M, Banks A, et al. Forkhead transcription factors (FoxOs) promote apoptosis of insulin-resistant macrophages during cholesterol-induced endoplasmic reticulum stress. Diabetes. 2008;57:2967-76 pubmed publisher
    ..Insulin-resistant macrophages showed attenuated Akt activation and increased nuclear localization of FoxO1 during endoplasmic reticulum stress induced by free cholesterol loading...
  70. Rached M, Kode A, Xu L, Yoshikawa Y, Paik J, Depinho R, et al. FoxO1 is a positive regulator of bone formation by favoring protein synthesis and resistance to oxidative stress in osteoblasts. Cell Metab. 2010;11:147-60 pubmed publisher
    ..Here we employ cell-specific deletion and molecular analyses to show that, among the three FoxO proteins, only FoxO1 is required for proliferation and redox balance in osteoblasts and thereby controls bone formation...
  71. Ouyang W, Beckett O, Flavell R, Li M. An essential role of the Forkhead-box transcription factor Foxo1 in control of T cell homeostasis and tolerance. Immunity. 2009;30:358-71 pubmed publisher
    ..Here we showed that T cell-specific deletion of Foxo1 gene in mice led to spontaneous T cell activation, effector T cell differentiation, autoantibody production, and ..
  72. Hashimoto N, Kido Y, Uchida T, Asahara S, Shigeyama Y, Matsuda T, et al. Ablation of PDK1 in pancreatic beta cells induces diabetes as a result of loss of beta cell mass. Nat Genet. 2006;38:589-93 pubmed
    ..Haploinsufficiency of the gene for the transcription factor Foxo1 resulted in a marked increase in the number, but not the size, of cells and resulted in the restoration of glucose ..
  73. Hoekman M, Jacobs F, Smidt M, Burbach J. Spatial and temporal expression of FoxO transcription factors in the developing and adult murine brain. Gene Expr Patterns. 2006;6:134-40 pubmed
    ..Here, we focus on three FoxO genes found to be expressed in the brain: FoxO1, FoxO3 and FoxO6...
  74. Qu S, Altomonte J, Perdomo G, He J, Fan Y, Kamagate A, et al. Aberrant Forkhead box O1 function is associated with impaired hepatic metabolism. Endocrinology. 2006;147:5641-52 pubmed
    b>FoxO1 plays an important role in mediating the effect of insulin on hepatic metabolism. Increased FoxO1 activity is associated with reduced ability of insulin to regulate hepatic glucose production...
  75. Talchai C, Xuan S, Kitamura T, Depinho R, Accili D. Generation of functional insulin-producing cells in the gut by Foxo1 ablation. Nat Genet. 2012;44:406-12, S1 pubmed publisher
    ..Here, we show that, unexpectedly, somatic ablation of Foxo1 in Neurog3(+) enteroendocrine progenitor cells gives rise to gut insulin-positive (Ins(+)) cells that express ..
  76. Fan W, Yanase T, Morinaga H, Okabe T, Nomura M, Daitoku H, et al. Insulin-like growth factor 1/insulin signaling activates androgen signaling through direct interactions of Foxo1 with androgen receptor. J Biol Chem. 2007;282:7329-38 pubmed
    ..Here we report that Foxo1, a downstream molecule that becomes phosphorylated and inactivated by phosphatidylinositol 3-kinase/Akt kinase in ..
  77. Xiong X, Tao R, Depinho R, Dong X. The autophagy-related gene 14 (Atg14) is regulated by forkhead box O transcription factors and circadian rhythms and plays a critical role in hepatic autophagy and lipid metabolism. J Biol Chem. 2012;287:39107-14 pubmed publisher
    ..Conversely, overexpression of Atg14 improves hypertriglyceridemia in both high fat diet-treated wild-type mice and FoxO1/3/4 liver-specific knock-out mice...
  78. Nakae J, Kitamura T, Kitamura Y, Biggs W, Arden K, Accili D. The forkhead transcription factor Foxo1 regulates adipocyte differentiation. Dev Cell. 2003;4:119-29 pubmed
    ..The forkhead transcription factor Foxo1 is regulated by insulin via Akt-dependent phosphorylation and nuclear exclusion...
  79. Adachi M, Osawa Y, Uchinami H, Kitamura T, Accili D, Brenner D. The forkhead transcription factor FoxO1 regulates proliferation and transdifferentiation of hepatic stellate cells. Gastroenterology. 2007;132:1434-46 pubmed
    ..Mutation/deletion mutants of FoxO1 were introduced into primary rat, mouse, and immortalized human HSCs and assessed for activation, proliferation, ..
  80. Sykes S, Lane S, Bullinger L, Kalaitzidis D, Yusuf R, Saez B, et al. AKT/FOXO signaling enforces reversible differentiation blockade in myeloid leukemias. Cell. 2011;146:697-708 pubmed publisher
    ..in human MLL-AF9 leukemia allele-induced AML in mice, where either activation of Akt or compound deletion of FoxO1/3/4 reduced leukemic cell growth, with the latter markedly diminishing leukemia-initiating cell (LIC) function in ..
  81. Kim J, Li P, Huntley J, Chang J, Arden K, Olefsky J. FoxO1 haploinsufficiency protects against high-fat diet-induced insulin resistance with enhanced peroxisome proliferator-activated receptor gamma activation in adipose tissue. Diabetes. 2009;58:1275-82 pubmed publisher
    ..Although the FoxO1 isoform is known to play a key role in adipogenesis, its physiological role in differentiated adipose tissue ..
  82. Tsuchiya K, Tanaka J, Shuiqing Y, Welch C, Depinho R, Tabas I, et al. FoxOs integrate pleiotropic actions of insulin in vascular endothelium to protect mice from atherosclerosis. Cell Metab. 2012;15:372-81 pubmed publisher
    ..The data demonstrate that FoxO inhibition in endothelial cells has the potential to mediate wide-ranging therapeutic benefits for diabetes-associated cardiovascular disease. ..
  83. Ouyang W, Beckett O, Ma Q, Paik J, Depinho R, Li M. Foxo proteins cooperatively control the differentiation of Foxp3+ regulatory T cells. Nat Immunol. 2010;11:618-27 pubmed publisher
    ..Here we show that mice with T cell-specific deletion of both the Foxo1 and Foxo3 transcription factors (collectively called 'Foxo proteins' here) developed a fatal multifocal ..