forkhead box protein o1


Summary: A forkhead box transcription factor that is a major target of INSULIN signaling and regulator of metabolic homeostasis in response to OXIDATIVE STRESS. It binds to the insulin RESPONSE ELEMENT (IRE) and the related Daf-16 family binding element (DBE). Its activity is suppressed by insulin and it also regulates OSTEOBLAST proliferation, controls bone mass, and skeletal regulation of GLUCOSE metabolism. It promotes GLUCONEOGENESIS in HEPATOCYTES and regulates gene expression in ADIPOSE TISSUE. It is also an important CELL DEATH regulator. Chromosomal aberrations involving the FOXO1 gene occur in RHABDOMYOSARCOMA.

Top Publications

  1. Zeng B, Huang Y, Xu J, Shiotsuki T, Bai H, Palli S, et al. The FOXO transcription factor controls insect growth and development by regulating juvenile hormone degradation in the silkworm, Bombyx mori. J Biol Chem. 2017;292:11659-11669 pubmed publisher
    ..mori In conclusion, we have uncovered a pivotal role for FOXO in regulating JH signaling to control insect development. ..
  2. Dongiovanni P, Meroni M, Baselli G, Bassani G, Rametta R, Pietrelli A, et al. Insulin resistance promotes Lysyl Oxidase Like 2 induction and fibrosis accumulation in non-alcoholic fatty liver disease. Clin Sci (Lond). 2017;131:1301-1315 pubmed publisher
    ..InsR+/- enhanced hepatic fat content and impaired hepatic insulin signaling leading to Forkhead box protein O1 (FoxO1) accumulation in MCD-fed mice...
  3. Oteiza A, Mechti N. FoxO4 negatively controls Tat-mediated HIV-1 transcription through the post-transcriptional suppression of Tat encoding mRNA. J Gen Virol. 2017;98:1864-1878 pubmed publisher
    ..Altogether, our findings demonstrate that FoxO factors can control HIV-1 transcription and provide new insights into their potential role during the establishment of HIV-1 latency. ..
  4. Zhang Y, Xie L, Gunasekar S, Tong D, Mishra A, Gibson W, et al. SWELL1 is a regulator of adipocyte size, insulin signalling and glucose homeostasis. Nat Cell Biol. 2017;19:504-517 pubmed publisher
    ..These studies identify SWELL1 as a cell-autonomous sensor of adipocyte size that regulates adipocyte growth, insulin sensitivity and glucose tolerance. ..
  5. Cai Z, Liu H, Wu X. Forkhead-box transcription factor 1 affects the apoptosis of natural regulatory T cells by controlling Aven expression. BMC Immunol. 2017;18:16 pubmed publisher
    Regulatory T (Treg) cells play important roles in autoimmune diseases, cancer, and organ transplantation. Forkhead box protein o1 (Foxo1) and IL-7R?(CD127) are closely related to the homeostasis of Treg cells...
  6. Yin J, Zhuang G, Zhu Y, Hu X, Zhao H, Zhang R, et al. MiR-615-3p inhibits the osteogenic differentiation of human lumbar ligamentum flavum cells via suppression of osteogenic regulators GDF5 and FOXO1. Cell Biol Int. 2017;41:779-786 pubmed publisher
    ..In conclusion, miR-615-3p negatively regulates the osteogenic differentiation of hLF cells through post-transcriptionally suppressing osteogenic regulators GDF5 and FOXO1. It can be regarded as a potential target for human OLF therapy. ..
  7. Lee J, Yang G, Kim Y, Tran Q, Choe W, Kang I, et al. Hydrogen-rich medium protects mouse embryonic fibroblasts from oxidative stress by activating LKB1-AMPK-FoxO1 signal pathway. Biochem Biophys Res Commun. 2017;491:733-739 pubmed publisher
  8. Gray S, Amezquita R, Guan T, Kleinstein S, Kaech S. Polycomb Repressive Complex 2-Mediated Chromatin Repression Guides Effector CD8+ T Cell Terminal Differentiation and Loss of Multipotency. Immunity. 2017;46:596-608 pubmed publisher
    ..These results outline a temporal model for loss of memory cell potential through selective epigenetic silencing of pro-memory genes in effector T cells. ..
  9. Zaal A, Nota B, Moore K, Dieker M, Van Ham S, ten Brinke A. TLR4 and C5aR crosstalk in dendritic cells induces a core regulatory network of RSK2, PI3K?, SGK1, and FOXO transcription factors. J Leukoc Biol. 2017;102:1035-1054 pubmed publisher
    ..Our findings shed new light on the depth and complexity of C5aR and TLR4 crosstalk and provide new foci of research for future studies. ..

More Information


  1. Agnihotri P, Robertson N, Umetsu S, Arakcheeva K, Winandy S. Lack of Ikaros cripples expression of Foxo1 and its targets in naive T cells. Immunology. 2017;152:494-506 pubmed publisher
    ..Together, these studies define, for the first time, a role for Ikaros in naive T cells and establish it as the first transcriptional regulator required for maintaining levels of Foxo1 gene expression in these cells. ..
  2. Essig K, Hu D, Guimaraes J, Alterauge D, Edelmann S, Raj T, et al. Roquin Suppresses the PI3K-mTOR Signaling Pathway to Inhibit T Helper Cell Differentiation and Conversion of Treg to Tfr Cells. Immunity. 2017;47:1067-1082.e12 pubmed publisher
    ..Thereby, Roquin-mediated control of PI3K-mTOR signaling prevents autoimmunity by restraining activation and differentiation of conventional T cells and specialization of Treg cells. ..
  3. Gopal K, Saleme B, Al Batran R, Aburasayn H, Eshreif A, Ho K, et al. FoxO1 regulates myocardial glucose oxidation rates via transcriptional control of pyruvate dehydrogenase kinase 4 expression. Am J Physiol Heart Circ Physiol. 2017;313:H479-H490 pubmed publisher
    ..Furthermore, we report here, for the first time, that FoxO1 inhibition increases glucose oxidation in the isolated working mouse heart. ..
  4. Nadya N, Tezuka H, Ohteki T, Matsuda S, Azuma M, Nagai S. PI3K-Akt pathway enhances the differentiation of interleukin-27-induced type 1 regulatory T cells. Immunology. 2017;152:507-516 pubmed publisher
    ..These results suggest that the PI3K pathway enhances IL-10 expression by IL-27-Tr1 cells through up-regulation of IL-21 receptors. ..
  5. Luo A, Yan H, Liang J, Du C, Zhao X, Sun L, et al. MicroRNA-21 regulates hepatic glucose metabolism by targeting FOXO1. Gene. 2017;627:194-201 pubmed publisher
    ..These results suggest that miR-21 is a critical regulator in hepatic gluconeogenesis and may provide a novel therapeutic target for treating insulin resistance and type 2 diabetes. ..
  6. Niimi K, Ueda M, Fukumoto M, Kohara M, Sawano T, Tsuchihashi R, et al. Transcription factor FOXO1 promotes cell migration toward exogenous ATP via controlling P2Y1 receptor expression in lymphatic endothelial cells. Biochem Biophys Res Commun. 2017;489:413-419 pubmed publisher
    ..These results indicated that FOXO1 serves a pivotal role in LEC migration toward exogenous ATP via direct transcriptional regulation of P2Y1 receptor. ..
  7. Guo S, Rena G, Cichy S, He X, Cohen P, Unterman T. Phosphorylation of serine 256 by protein kinase B disrupts transactivation by FKHR and mediates effects of insulin on insulin-like growth factor-binding protein-1 promoter activity through a conserved insulin response sequence. J Biol Chem. 1999;274:17184-92 pubmed
    ..Signaling to FKHR-related forkhead proteins via PKB may provide an evolutionarily conserved mechanism by which insulin and related factors regulate gene expression. ..
  8. Chen Y, Wang S, He Z, Sun F, Huang Y, Ni Q, et al. Dyrk1B overexpression is associated with breast cancer growth and a poor prognosis. Hum Pathol. 2017;66:48-58 pubmed publisher
    ..The results suggest that Dyrk1B plays a key role in the progression of breast cancer and provides a new target for breast cancer therapy. ..
  9. Li Y, Yang P, Chang Q, Wang J, Liu J, Lv Y, et al. Inhibitory Effect of Piceatannol on TNF-?-Mediated Inflammation and Insulin Resistance in 3T3-L1 Adipocytes. J Agric Food Chem. 2017;65:4634-4641 pubmed publisher
    ..These results suggested the potential of piceatannol in improving chronic inflammatory condition and insulin sensitivity in obese adipose tissues. ..
  10. Lin S, Ptasinska A, Chen X, Shrestha M, Assi S, Chin P, et al. A FOXO1-induced oncogenic network defines the AML1-ETO preleukemic program. Blood. 2017;130:1213-1222 pubmed publisher
    ..Targeting of FOXO1 therefore provides a potential therapeutic strategy for elimination of stem cells at both preleukemic and leukemic stages. ..
  11. Li W, Du M, Wang Q, Ma X, Wu L, Guo F, et al. FoxO1 Promotes Mitophagy in the Podocytes of Diabetic Male Mice via the PINK1/Parkin Pathway. Endocrinology. 2017;158:2155-2167 pubmed publisher
    ..Our results link the antioxidative activity of FoxO1 with PINK1/Parkin-induced mitophagy, indicating a novel role of FoxO1 in diabetic nephropathy. ..
  12. Sowell R, Goldufsky J, Rogozinska M, Quiles Z, Cao Y, Castillo E, et al. IL-15 Complexes Induce Migration of Resting Memory CD8 T Cells into Mucosal Tissues. J Immunol. 2017;199:2536-2546 pubmed publisher
    ..This study provides mechanistic insight into how IL-15 controls the generation of memory CD8 T cells and influences their trafficking and ability to take up residence within peripheral tissues. ..
  13. Yang Y, Blee A, Wang D, An J, Pan Y, Yan Y, et al. Loss of FOXO1 Cooperates with TMPRSS2-ERG Overexpression to Promote Prostate Tumorigenesis and Cell Invasion. Cancer Res. 2017;77:6524-6537 pubmed publisher
    ..Our findings enhance understanding of prostate cancer etiology and suggest that the FOXO1-ERG signaling axis can be a potential target for treatment of prostate cancer. Cancer Res; 77(23); 6524-37. ©2017 AACR. ..
  14. Choi R, McConahay A, Jeong H, McClellan J, Hardee J, Carson J, et al. Tribbles 3 regulates protein turnover in mouse skeletal muscle. Biochem Biophys Res Commun. 2017;493:1236-1242 pubmed publisher
    ..These findings indicate that TRB3 regulates protein synthesis and breakdown via the Akt/mTOR/FoxO pathways. ..
  15. Sim M, Huynh H, Go M, Yuen J. Action of YM155 on clear cell renal cell carcinoma does not depend on survivin expression levels. PLoS ONE. 2017;12:e0178168 pubmed publisher
    ..It also implied that the expression of other oncogenic proteins which YM155 may target is either low or absent in this clear cell RCC. ..
  16. Choi Y, Park J, Ko Y, Kim Y, Pyo J, Jang B, et al. FOXO1 reduces tumorsphere formation capacity and has crosstalk with LGR5 signaling in gastric cancer cells. Biochem Biophys Res Commun. 2017;493:1349-1355 pubmed publisher
    ..Taken together, our results suggest that FOXO1 inhibits the self-renewal capacity of GC cells through interaction with LGR5. Thus, FOXO1/LGR5 signaling pathway may provide a novel targeted therapy for GC...
  17. Tong X, Zhang D, Charney N, Jin E, VanDommelen K, Stamper K, et al. DDB1-Mediated CRY1 Degradation Promotes FOXO1-Driven Gluconeogenesis in Liver. Diabetes. 2017;66:2571-2582 pubmed publisher
    ..Thus, we have identified the DDB1-mediated CRY1 degradation as an important target of insulin action on glucose homeostasis. ..
  18. Kurkewich J, Hansen J, Klopfenstein N, Zhang H, Wood C, Boucher A, et al. The miR-23a~27a~24-2 microRNA cluster buffers transcription and signaling pathways during hematopoiesis. PLoS Genet. 2017;13:e1006887 pubmed publisher
    ..In summary, our data demonstrates that mirn23a regulates a complex array of transcription and signaling pathways to modulate adult hematopoiesis. ..
  19. Medema R, Jaattela M. Cytosolic FoxO1: alive and killing. Nat Cell Biol. 2010;12:642-3 pubmed publisher
    ..Cytosolic FoxO1 can also suppress tumour growth by triggering autophagy and ultimately cell death in a transcription-independent manner. ..
  20. Sarem Z, Bumke Vogt C, Mahmoud A, Assefa B, Weickert M, Adamidou A, et al. Glucagon Decreases IGF-1 Bioactivity in Humans, Independently of Insulin, by Modulating Its Binding Proteins. J Clin Endocrinol Metab. 2017;102:3480-3490 pubmed publisher
    ..The effect of glucagon on the transcription factor forkhead box protein O1 (FOXO1) translocation, the transcription of GH/IGF-1 system members, and phosphorylation of protein ..
  21. Stern M. Evidence that a mitochondrial death spiral underlies antagonistic pleiotropy. Aging Cell. 2017;16:435-443 pubmed publisher
    ..I suggest that the mitochondrial death spiral is not an error in cell physiology but rather a rational approach to the problem of enabling successful growth and reproduction in a competitive world of scarce nutrients...
  22. Wu J, Shao C, Li X, Li Q, Hu P, Shi C, et al. Monoamine oxidase A mediates prostate tumorigenesis and cancer metastasis. J Clin Invest. 2014;124:2891-908 pubmed publisher
    ..These findings collectively characterize the contribution of MAOA in PCa pathogenesis and suggest that MAOA has potential as a therapeutic target in PCa. ..
  23. Xu X, Ji S, Li W, Yi B, Li H, Zhang H, et al. LncRNA H19 promotes the differentiation of bovine skeletal muscle satellite cells by suppressing Sirt1/FoxO1. Cell Mol Biol Lett. 2017;22:10 pubmed publisher
    ..H19 promoted the differentiation of bovine skeletal muscle satellite cells by suppressing Sirt1/FoxO1. ..
  24. Feinberg M. OutFOXing myeloid cells in atherosclerosis with FoxOs. Circ Res. 2013;112:978-82 pubmed publisher
  25. Ismayilnajadteymurabadi H, Konukoglu D. The relationship between preptin, Forkhead box protein O1 and mechanistic target of rapamycin levels in prediabetic patients. J Biol Regul Homeost Agents. 2017;31:399-405 pubmed
    ..Indeed, mTOR-mediated variations in cellular level from female patients and FOXO-1-mediated variations of male patients indicated that these factors might play a critical role in glucose intolerance. ..
  26. Liu L, Liu Y, Yuan M, Xu L, Sun H. Elevated expression of microRNA-873 facilitates Th17 differentiation by targeting forkhead box O1 (Foxo1) in the pathogenesis of systemic lupus erythematosus. Biochem Biophys Res Commun. 2017;492:453-460 pubmed publisher
    ..In vivo blockade of miR-873 may serve as a novel therapeutic approach in the treatment of SLE. ..
  27. West G, Rodia C, Li D, Johnson Z, Dong H, Kohan A. Key differences between apoC-III regulation and expression in intestine and liver. Biochem Biophys Res Commun. 2017;491:747-753 pubmed publisher
  28. Langlet F, Haeusler R, Lindén D, Ericson E, Norris T, Johansson A, et al. Selective Inhibition of FOXO1 Activator/Repressor Balance Modulates Hepatic Glucose Handling. Cell. 2017;171:824-835.e18 pubmed publisher
    ..In addition to identifying a novel mode of insulin action, these data raise the possibility of developing selective modulators of unliganded transcription factors to dial out adverse effects of insulin sensitizers. ..
  29. Liu J, Zhang L, Yao J, Yao S, Yuan T. AMPK alleviates endoplasmic reticulum stress by inducing the ER-chaperone ORP150 via FOXO1 to protect human bronchial cells from apoptosis. Biochem Biophys Res Commun. 2018;497:564-570 pubmed publisher
    ..Thus, AMPK may serve as a likely therapeutic target for clinical and sub-clinical interventions in COPD. ..
  30. Dor Y, Glaser B. ?-cell dedifferentiation and type 2 diabetes. N Engl J Med. 2013;368:572-3 pubmed publisher
  31. Zhou G, Wang X, Yuan C, Kang D, Xu X, Zhou J, et al. Integrating miRNA and mRNA Expression Profiling Uncovers miRNAs Underlying Fat Deposition in Sheep. Biomed Res Int. 2017;2017:1857580 pubmed publisher
    ..These pathways included the MAPK signaling pathway, FoxO and Wnt signaling pathway, and focal adhesion. Taken together, our results define miRNA expression signatures that may contribute to fat deposition and lipid metabolism in sheep. ..
  32. Irimia J, Meyer C, Segvich D, Surendran S, DePaoli Roach A, Morral N, et al. Lack of liver glycogen causes hepatic insulin resistance and steatosis in mice. J Biol Chem. 2017;292:10455-10464 pubmed publisher
    ..Our results suggest that loss of liver glycogen synthesis diverts glucose toward fat synthesis, correlating with impaired hepatic insulin signaling and glucose disposal. ..
  33. Sereni M, Baldelli E, Gambara G, Ravaggi A, Hodge K, Alberts D, et al. Kinase-driven metabolic signalling as a predictor of response to carboplatin-paclitaxel adjuvant treatment in advanced ovarian cancers. Br J Cancer. 2017;117:494-502 pubmed publisher
    ..If validated in a larger cohort of patients, the decreased AMPK-AKT-mTOR activation and phosphorylation of FOXO1 T24/FOXO3 T32 may help identify carboplatin-paclitaxel-resistant EOC patients. ..
  34. Yang W, Hong L, Xu X, Wang Q, Huang J, Jiang L. LncRNA GAS5 suppresses the tumorigenesis of cervical cancer by downregulating miR-196a and miR-205. Tumour Biol. 2017;39:1010428317711315 pubmed publisher
    ..The expression of GAS5, forkhead box protein O1 and phosphatase and tensin homolog was examined by quantitative reverse transcription polymerase chain ..
  35. Panagopoulos I, Gorunova L, Lobmaier I, Andersen H, Bjerkehagen B, Heim S. Cytogenetic Analysis of a Pseudoangiomatous Pleomorphic/Spindle Cell Lipoma. Anticancer Res. 2017;37:2219-2223 pubmed
    ..Among them was loss of chromosome 13 material. Results confirm the (cyto)genetic similarity between pseudoangiomatous pleomorphic/spindle cell lipoma and spindle cell lipomas. ..
  36. Liu S, Cheng C. Akt Signaling Is Sustained by a CD44 Splice Isoform-Mediated Positive Feedback Loop. Cancer Res. 2017;77:3791-3801 pubmed publisher
    ..i>Cancer Res; 77(14); 3791-801. ©2017 AACR. ..
  37. Ubieta K, García M, Grötsch B, Uebe S, Weber G, Stein M, et al. Fra-2 regulates B cell development by enhancing IRF4 and Foxo1 transcription. J Exp Med. 2017;214:2059-2071 pubmed publisher
    ..Hence, Fra-2 is a key upstream regulator of Foxo1 and Irf4 expression and influences proliferation and differentiation of B cells at multiple stages. ..
  38. Bergman R, Iyer M. Indirect Regulation of Endogenous Glucose Production by Insulin: The Single Gateway Hypothesis Revisited. Diabetes. 2017;66:1742-1747 pubmed publisher
    ..The knockout mouse model in combination with sophisticated molecular techniques confirmed our physiological findings and the single gateway hypothesis. ..
  39. Sasaki M, Sasako T, Kubota N, Sakurai Y, Takamoto I, Kubota T, et al. Dual Regulation of Gluconeogenesis by Insulin and Glucose in the Proximal Tubules of the Kidney. Diabetes. 2017;66:2339-2350 pubmed publisher
  40. Li H, Li Y, Xiang L, Zhang J, ZHu B, Xiang L, et al. GDF11 Attenuates Development of Type 2 Diabetes via Improvement of Islet ?-Cell Function and Survival. Diabetes. 2017;66:1914-1927 pubmed publisher
    ..These findings suggest that GDF11 repletion may improve ?-cell function and mass and thus may lead to a new therapeutic approach for T2D. ..
  41. Xiong Y, Zhang Y, Xin N, Yuan Y, Zhang Q, Gong P, et al. 1?,25-Dihydroxyvitamin D3 promotes osteogenesis by promoting Wnt signaling pathway. J Steroid Biochem Mol Biol. 2017;174:153-160 pubmed publisher
    ..This study also provides a novel understanding of the effect of 1,25(OH)2D3 on skeleton in oxidative stress condition. ..
  42. Jo E, Li S, Liang Q, Zhang X, Wang H, Herbert T, et al. Chronic activation of PPAR? with fenofibrate reduces autophagic proteins in the liver of mice independent of FGF21. PLoS ONE. 2017;12:e0173676 pubmed publisher
    ..These findings suggest that chronic stimulation of PPAR? may suppress the autophagy capacity in the liver as a result of reduced content of a number of autophagy-associated proteins independent of FGF21. ..
  43. Shi Y, Qiao J, Mu B, Zuo B, Yuan J. 3-(2-amino-ethyl)-5-[3-(4-butoxyl-phenyl)-propylidene]-thiazolidine-2,4-dione (K145) ameliorated dexamethasone induced hepatic gluconeogenesis through activation of Akt/FoxO1 pathway. Biochem Biophys Res Commun. 2017;493:286-290 pubmed publisher
    ..Our study figures out a potential extent increase the value of developing K145 as therapeutic candidate for diabetes. ..
  44. Chan L, MUSCHEN M. B-cell identity as a metabolic barrier against malignant transformation. Exp Hematol. 2017;53:1-6 pubmed publisher
  45. Huang Z, Kataoka M, Chen J, Wu G, Ding J, Nie M, et al. Cardiomyocyte-enriched protein CIP protects against pathophysiological stresses and regulates cardiac homeostasis. J Clin Invest. 2015;125:4122-34 pubmed publisher
    ..Our studies identify CIP as a key regulator of cardiomyopathy that has potential as a therapeutic target to attenuate heart failure progression. ..
  46. Leibel R, Seeley R, Darsow T, Berg E, Smith S, Ratner R. Biologic Responses to Weight Loss and Weight Regain: Report From an American Diabetes Association Research Symposium. Diabetes. 2015;64:2299-309 pubmed publisher
  47. Cheng Z, White M. The AKTion in non-canonical insulin signaling. Nat Med. 2012;18:351-3 pubmed publisher
  48. Ogg S, Paradis S, Gottlieb S, Patterson G, Lee L, Tissenbaum H, et al. The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature. 1997;389:994-9 pubmed
    ..The probable human orthologues of DAF-16, FKHR and AFX, may also act downstream of insulin signalling and cooperate with TGF-beta effectors in mediating metabolic regulation. These genes may be dysregulated in diabetes. ..
  49. Sreekumar A, Toneff M, Toh E, Roarty K, Creighton C, Belka G, et al. WNT-Mediated Regulation of FOXO1 Constitutes a Critical Axis Maintaining Pubertal Mammary Stem Cell Homeostasis. Dev Cell. 2017;43:436-448.e6 pubmed publisher
    ..Together, these data suggest that the WNT pathway confers proliferative and survival advantages on cap cells via regulation of FOXO1 localization. ..
  50. Jiang J, Liu Z, Ge C, Chen C, Zhao F, Li H, et al. NK3 homeobox 1 (NKX3.1) up-regulates forkhead box O1 expression in hepatocellular carcinoma and thereby suppresses tumor proliferation and invasion. J Biol Chem. 2017;292:19146-19159 pubmed publisher
    ..These results suggest that NKX3.1 functions as a tumor suppressor in HCC cells through directly up-regulating FOXO1 expression. ..
  51. Jiang J, Huang Z, Chen X, Luo R, Cai H, Wang H, et al. Trifluoperazine Activates FOXO1-Related Signals to Inhibit Tumor Growth in Hepatocellular Carcinoma. DNA Cell Biol. 2017;36:813-821 pubmed publisher