Gene Symbol: FKHRL1
Description: forkhead box O3
Alias: AF6q21, FKHRL1, FKHRL1P2, FOXO2, FOXO3A, forkhead box protein O3, forkhead box O3A, forkhead homolog (rhabdomyosarcoma) like 1, forkhead in rhabdomyosarcoma-like 1, forkhead, Drosophila, homolog of, in rhabdomyosarcoma-like 1
Species: human
Products:     FKHRL1

Top Publications

  1. Brunet A, Bonni A, Zigmond M, Lin M, Juo P, Hu L, et al. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell. 1999;96:857-68 pubmed
    ..In this study, we demonstrate that Akt also regulates the activity of FKHRL1, a member of the Forkhead family of transcription factors...
  2. Essaghir A, Dif N, Marbehant C, Coffer P, Demoulin J. The transcription of FOXO genes is stimulated by FOXO3 and repressed by growth factors. J Biol Chem. 2009;284:10334-42 pubmed publisher
    ..Altogether, our results suggest that the expression of FOXO1 and FOXO4 genes is stimulated by FOXO3 and possibly by other FOXO factors in a positive feedback loop, which is disrupted by growth factors. ..
  3. Dabrowska A, Kim N, Aldovini A. Tat-induced FOXO3a is a key mediator of apoptosis in HIV-1-infected human CD4+ T lymphocytes. J Immunol. 2008;181:8460-77 pubmed
    ..response-1/phosphate and tensin homolog deleted on chromosome 10/Akt) and p53 pathways, which converge on the FOXO3a (Forkhead box transcription factor O class 3a) transcriptional activator...
  4. Zhu W, Bijur G, Styles N, Li X. Regulation of FOXO3a by brain-derived neurotrophic factor in differentiated human SH-SY5Y neuroblastoma cells. Brain Res Mol Brain Res. 2004;126:45-56 pubmed
    b>FOXO3a is a ubiquitously expressed mammalian forkhead transcription factor with a high expression level in adult brain...
  5. van Grevenynghe J, Procopio F, He Z, Chomont N, Riou C, Zhang Y, et al. Transcription factor FOXO3a controls the persistence of memory CD4(+) T cells during HIV infection. Nat Med. 2008;14:266-74 pubmed publisher
    ..We show that persistence of T(CM) cells from EC subjects is a direct consequence of inactivation of the FOXO3a pathway...
  6. Kikuchi S, Nagai T, Kunitama M, Kirito K, Ozawa K, Komatsu N. Active FKHRL1 overcomes imatinib resistance in chronic myelogenous leukemia-derived cell lines via the production of tumor necrosis factor-related apoptosis-inducing ligand. Cancer Sci. 2007;98:1949-58 pubmed
    b>FKHRL1 (also called FOXO3a) is a member of the Forkhead Box, class O (FOXO) subfamily of forkhead transcription factors and functions downstream of Bcr-Abl tyrosine kinase as a phosphorylated inactive form in chronic myelogenous leukemia (..
  7. Hu M, Lee D, Xia W, Golfman L, Ou Yang F, Yang J, et al. IkappaB kinase promotes tumorigenesis through inhibition of forkhead FOXO3a. Cell. 2004;117:225-37 pubmed
    Nuclear exclusion of the forkhead transcription factor FOXO3a by protein kinase Akt contributes to cell survival. We investigated the pathological relationship between phosphoylated-Akt (Akt-p) and FOXO3a in primary tumors...
  8. Zheng W, Kar S, Quirion R. Insulin-like growth factor-1-induced phosphorylation of the forkhead family transcription factor FKHRL1 is mediated by Akt kinase in PC12 cells. J Biol Chem. 2000;275:39152-8 pubmed
    The Forkhead family transcription factor FKHRL1, a mammalian homolog of DAF16 in the nematode Caenorhabditis elegans, is an inducer of apoptosis in its unphosphorylated form and was recently reported as a substrate of Akt kinases...
  9. Wang K, Li P. Foxo3a regulates apoptosis by negatively targeting miR-21. J Biol Chem. 2010;285:16958-66 pubmed publisher
    ..Here we report that the transcriptional factor Foxo3a initiates apoptosis by transcriptionally repressing miR-21 expression...

More Information

Publications120 found, 100 shown here

  1. Kress T, Cannell I, Brenkman A, 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;41:445-57 pubmed publisher
    ..MK5 activates miR-34b/c expression via phosphorylation of FoxO3a, thereby promoting nuclear localization of FoxO3a and enabling it to induce miR-34b/c expression and arrest ..
  2. 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 phosphorylation at AKT ..
  3. Sisci D, Maris P, Cesario M, Anselmo W, Coroniti R, Trombino G, et al. The estrogen receptor ? is the key regulator of the bifunctional role of FoxO3a transcription factor in breast cancer motility and invasiveness. Cell Cycle. 2013;12:3405-20 pubmed publisher
    ..Here we show that FoxO3a overexpression decreases motility, invasiveness, and anchorage-independent growth in estrogen receptor ?-positive (..
  4. Potente M, Urbich C, Sasaki K, Hofmann W, Heeschen C, Aicher A, et al. Involvement of Foxo transcription factors in angiogenesis and postnatal neovascularization. J Clin Invest. 2005;115:2382-92 pubmed
    ..Here, we show that Foxo1 and Foxo3a are the most abundant Foxo isoforms in mature endothelial cells and that overexpression of constitutively active ..
  5. Zhu S, Evans S, Yan B, Povsic T, Tapson V, Goldschmidt Clermont P, et al. Transcriptional regulation of Bim by FOXO3a and Akt mediates scleroderma serum-induced apoptosis in endothelial progenitor cells. Circulation. 2008;118:2156-65 pubmed publisher
    ..of Akt, which in turn suppressed the phosphorylation and degradation of forkhead transcription factor FKHRL1 (FOXO3a), resulting in the upregulation of apoptotic protein Bim...
  6. Brunet A, Kanai F, Stehn J, Xu J, Sarbassova D, Frangioni J, et al. 14-3-3 transits to the nucleus and participates in dynamic nucleocytoplasmic transport. J Cell Biol. 2002;156:817-28 pubmed
    ..We demonstrate that phosphorylation of one important 14-3-3 binding molecule, the transcription factor FKHRL1, at the 14-3-3 binding site occurs within the nucleus immediately before FKHRL1 relocalization to the cytoplasm...
  7. Madureira P, Varshochi R, Constantinidou D, Francis R, Coombes R, Yao K, et al. The Forkhead box M1 protein regulates the transcription of the estrogen receptor alpha in breast cancer cells. J Biol Chem. 2006;281:25167-76 pubmed
    ..Further co-immunoprecipitation experiments showed that FoxO3a and FoxM1 interact in vivo...
  8. Hwang J, Rajendrasozhan S, Yao H, Chung S, Sundar I, Huyck H, et al. FOXO3 deficiency leads to increased susceptibility to cigarette smoke-induced inflammation, airspace enlargement, and chronic obstructive pulmonary disease. J Immunol. 2011;187:987-98 pubmed publisher
    ..These results suggest that FoxO3 plays a pivotal role in regulation of lung inflammatory response and antioxidant genes, and deficiency of FoxO3 results in development of chronic obstructive pulmonary disease/emphysema. ..
  9. Wang F, Chan C, Chen K, Guan X, Lin H, Tong Q. Deacetylation of FOXO3 by SIRT1 or SIRT2 leads to Skp2-mediated FOXO3 ubiquitination and degradation. Oncogene. 2012;31:1546-57 pubmed publisher
    ..Taken together, our data support the notion that deacetylation of FOXO3 by SIRT1 or SIRT2 facilitates Skp2-mediated FOXO3 poly-ubiquitination and proteasomal degradation. ..
  10. Eijkelenboom A, Mokry M, de Wit E, Smits L, Polderman P, van Triest M, et al. Genome-wide analysis of FOXO3 mediated transcription regulation through RNA polymerase II profiling. Mol Syst Biol. 2013;9:638 pubmed publisher
    ..Combined, our data elucidate how FOXOs regulate gene transcription and provide insight into mechanisms by which FOXOs can induce different gene expression programs depending on chromatin architecture. ..
  11. Fei M, Zhao Y, Wang Y, Lu M, Cheng C, Huang X, et al. Low expression of Foxo3a is associated with poor prognosis in ovarian cancer patients. Cancer Invest. 2009;27:52-9 pubmed publisher
    To investigate whether Foxo3a expression is correlated with p27(kip1) protein levels as well as how it might be clinically relevant, we evaluated the expression of Foxo3a in several ovarian tumors...
  12. Tsai K, Sun Y, Huang C, Yang J, Hung M, Hsiao C. Crystal structure of the human FOXO3a-DBD/DNA complex suggests the effects of post-translational modification. Nucleic Acids Res. 2007;35:6984-94 pubmed
    b>FOXO3a is a transcription factor of the FOXO family...
  13. Soerensen M, Dato S, Christensen K, McGue M, Stevnsner T, Bohr V, et al. Replication of an association of variation in the FOXO3A gene with human longevity using both case-control and longitudinal data. Aging Cell. 2010;9:1010-7 pubmed publisher
    Genetic variation in FOXO3A has previously been associated with human longevity. Studies published so far have been case-control studies and hence vulnerable to bias introduced by cohort effects...
  14. Jensen K, Binderup T, Jensen K, Therkelsen I, Borup R, Nilsson E, et al. FoxO3A promotes metabolic adaptation to hypoxia by antagonizing Myc function. EMBO J. 2011;30:4554-70 pubmed publisher
    ..Here, we show that FoxO3A is activated in hypoxia downstream of HIF-1 and mediates the hypoxic repression of a set of nuclear-encoded ..
  15. Fernandez De Mattos S, Essafi A, Soeiro I, Pietersen A, Birkenkamp K, Edwards C, et al. FoxO3a and BCR-ABL regulate cyclin D2 transcription through a STAT5/BCL6-dependent mechanism. Mol Cell Biol. 2004;24:10058-71 pubmed
    ..this study, we used the BCR-ABL-expressing cell line BV173 as a model system to investigate the mechanisms whereby FoxO3a regulates cyclin D2 expression...
  16. Yang J, Zong C, Xia W, Yamaguchi H, Ding Q, Xie X, et al. ERK promotes tumorigenesis by inhibiting FOXO3a via MDM2-mediated degradation. Nat Cell Biol. 2008;10:138-48 pubmed publisher
    ..Here, we show that Erk downregulates Forkhead box O 3a (FOXO3a) by directly interacting with and phosphorylating FOXO3a at Ser 294, Ser 344 and Ser 425, which consequently ..
  17. Medema R, Kops G, Bos J, Burgering B. AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1. Nature. 2000;404:782-7 pubmed
    ..We conclude that AFX-like proteins are involved in cell-cycle regulation and that inactivation of these proteins is an important step in oncogenic transformation. ..
  18. Bakker W, Blázquez Domingo M, Kolbus A, Besooyen J, Steinlein P, Beug H, et al. FoxO3a regulates erythroid differentiation and induces BTG1, an activator of protein arginine methyl transferase 1. J Cell Biol. 2004;164:175-84 pubmed
    ..b>FoxO3a expression and nuclear accumulation increased during erythroid differentiation, whereas untimely induction of ..
  19. Obexer P, Hagenbuchner J, Unterkircher T, Sachsenmaier N, Seifarth C, Böck G, et al. Repression of BIRC5/survivin by FOXO3/FKHRL1 sensitizes human neuroblastoma cells to DNA damage-induced apoptosis. Mol Biol Cell. 2009;20:2041-8 pubmed publisher
    ..Here, we show that inhibition of PI3K-PKB signaling in human NB cells induces nuclear translocation of FOXO3/FKHRL1, represses the prosurvival protein BIRC5/Survivin, and sensitizes to DNA-damaging agents...
  20. Modur V, Nagarajan R, Evers B, Milbrandt J. FOXO proteins regulate tumor necrosis factor-related apoptosis inducing ligand expression. Implications for PTEN mutation in prostate cancer. J Biol Chem. 2002;277:47928-37 pubmed
    ..3-kinase pathway and a resultant loss of activity of the FOXO family of forkhead transcription factors FKHRL1 and FKHR...
  21. Kornblau S, Singh N, Qiu Y, Chen W, Zhang N, Coombes K. Highly phosphorylated FOXO3A is an adverse prognostic factor in acute myeloid leukemia. Clin Cancer Res. 2010;16:1865-74 pubmed publisher
    ..This study evaluated the level of expression and the prognostic relevance of total and phosphorylated FOXO3A protein in AML...
  22. Lu M, Xiang J, Xu F, Wang Y, Yin Y, Chen D. The expression and significance of pThr32-FOXO3a in human ovarian cancer. Med Oncol. 2012;29:1258-64 pubmed publisher
    b>FOXO3a possesses a large series function, including cellular proliferation, transformation, differentiation, and longevity...
  23. Essers M, de Vries Smits L, Barker N, Polderman P, Burgering B, Korswagen H. Functional interaction between beta-catenin and FOXO in oxidative stress signaling. Science. 2005;308:1181-4 pubmed
    ..These results demonstrate a role for beta-catenin in regulating FOXO function that is particularly important under conditions of oxidative stress. ..
  24. Tsai W, Chung Y, Takahashi Y, Xu Z, Hu M. Functional interaction between FOXO3a and ATM regulates DNA damage response. Nat Cell Biol. 2008;10:460-7 pubmed publisher
    ..Here, we show that FOXO3a interacts with ATM to promote phosphorylation of ATM at Ser 1981 and prompting its downstream mediators to form ..
  25. Shukla S, Shukla M, MacLennan G, Fu P, Gupta S. Deregulation of FOXO3A during prostate cancer progression. Int J Oncol. 2009;34:1613-20 pubmed
    Forkhead box transcription factor FOXO3A, an important regulator of cellular function, is thought to act as a tumor suppressor. We studied whether alterations in FOXO3A activity occur in prostate tumorigenesis...
  26. Mikse O, Blake D, Jones N, Sun Y, Amin S, Gallagher C, et al. FOXO3 encodes a carcinogen-activated transcription factor frequently deleted in early-stage lung adenocarcinoma. Cancer Res. 2010;70:6205-15 pubmed publisher
    ..Here, we show that FOXO3a is functionally activated and augments the level of caspase-dependent apoptosis in cells exposed to this DNA-..
  27. Schuur E, Loktev A, Sharma M, Sun Z, Roth R, Weigel R. Ligand-dependent interaction of estrogen receptor-alpha with members of the forkhead transcription factor family. J Biol Chem. 2001;276:33554-60 pubmed
    ..The related family members, FKHRL1 and AFX, also bound to ER alpha in the presence of beta-estradiol...
  28. Lynch R, Konicek B, McNulty A, Hanna K, Lewis J, Neubauer B, et al. The progression of LNCaP human prostate cancer cells to androgen independence involves decreased FOXO3a expression and reduced p27KIP1 promoter transactivation. Mol Cancer Res. 2005;3:163-9 pubmed
    ..The FOXO3a protein, the most highly expressed FOXO family member in prostate cancer cells, is hyperphosphorylated in LNAI ..
  29. Tan W, Wang K, Lv D, Li P. Foxo3a inhibits cardiomyocyte hypertrophy through transactivating catalase. J Biol Chem. 2008;283:29730-9 pubmed publisher
    The forkhead transcription factor Foxo3a is able to inhibit cardiomyocyte hypertrophy. However, its underlying molecular mechanism remains to be fully understood...
  30. Storz P, Döppler H, Copland J, Simpson K, Toker A. FOXO3a promotes tumor cell invasion through the induction of matrix metalloproteinases. Mol Cell Biol. 2009;29:4906-17 pubmed publisher
    The role of the Forkhead transcription factor FOXO3a in processes that promote tumor metastasis is poorly defined...
  31. Banasik K, Ribel Madsen R, Gjesing A, Wegner L, Andersson A, Poulsen P, et al. The FOXO3A rs2802292 G-allele associates with improved peripheral and hepatic insulin sensitivity and increased skeletal muscle-FOXO3A mRNA expression in twins. J Clin Endocrinol Metab. 2011;96:E119-24 pubmed publisher
    The minor G-allele of FOXO3A rs2802292 has been associated with longevity...
  32. Lee H, Youn S, Kim J, Park K, Hwang C, Park W, et al. FOXO3a turns the tumor necrosis factor receptor signaling towards apoptosis through reciprocal regulation of c-Jun N-terminal kinase and NF-kappaB. Arterioscler Thromb Vasc Biol. 2008;28:112-20 pubmed
    We evaluated the full range effects of FOXO3a in endothelial cells (ECs) by microarray analysis and investigated the role of FOXO3a regulating TNF receptor signaling pathway...
  33. McGovern U, Francis R, Peck B, Guest S, Wang J, Myatt S, et al. Gefitinib (Iressa) represses FOXM1 expression via FOXO3a in breast cancer. Mol Cancer Ther. 2009;8:582-91 pubmed publisher
    ..FOXM1 repression by gefitinib is associated with FOXO3a activation and is mediated at the transcriptional level and gene promoter level...
  34. Karube K, Nakagawa M, Tsuzuki S, Takeuchi I, Honma K, Nakashima Y, et al. Identification of FOXO3 and PRDM1 as tumor-suppressor gene candidates in NK-cell neoplasms by genomic and functional analyses. Blood. 2011;118:3195-204 pubmed publisher
    ..PRDM1 and FOXO3 are considered to play an important role in the pathogenesis of NK-cell neoplasms. ..
  35. Chatterjee A, Chatterjee U, Ghosh M. Activation of protein kinase CK2 attenuates FOXO3a functioning in a PML-dependent manner: implications in human prostate cancer. Cell Death Dis. 2013;4:e543 pubmed publisher
    ..One of the immediate consequences, of this inactivation is the stabilization of FOXO3a, another well-established tumor suppressor, inside the nucleus and its downstream activities...
  36. Lee H, Chung J, Youn S, Kim J, Park K, Koo B, et al. Forkhead transcription factor FOXO3a is a negative regulator of angiogenic immediate early gene CYR61, leading to inhibition of vascular smooth muscle cell proliferation and neointimal hyperplasia. Circ Res. 2007;100:372-80 pubmed
    ..We hypothesized that the forkhead transcription factor FOXO3a may regulate CYR61 expression in VSMCs and investigated the CYR61-modulating effect of FOXO3a in the process of ..
  37. Flachsbart F, Caliebe A, Kleindorp R, Blanche H, von Eller Eberstein H, Nikolaus S, et al. Association of FOXO3A variation with human longevity confirmed in German centenarians. Proc Natl Acad Sci U S A. 2009;106:2700-5 pubmed publisher
    The human forkhead box O3A gene (FOXO3A) encodes an evolutionarily conserved key regulator of the insulin-IGF1 signaling pathway that is known to influence metabolism and lifespan in model organisms...
  38. Donlon T, Curb J, He Q, Grove J, Masaki K, Rodriguez B, et al. FOXO3 gene variants and human aging: coding variants may not be key players. J Gerontol A Biol Sci Med Sci. 2012;67:1132-9 pubmed publisher
    ..Furthermore, we identified a novel, unique, nonsynonymous coding variant in exon 3 (Gly566Ala; rs138174682) that is prevalent in multiple ethnic groups but appeared too rare for major longevity effects in our study populations. ..
  39. Delpuech O, Griffiths B, East P, Essafi A, Lam E, Burgering B, et al. Induction of Mxi1-SR alpha by FOXO3a contributes to repression of Myc-dependent gene expression. Mol Cell Biol. 2007;27:4917-30 pubmed
    ..Using DNA microarrays, we analyzed the transcriptional response to FOXO3a activation by gene expression analysis in DLD-1 colon cancer cells stably expressing a FOXO3a.A3-ER fusion protein...
  40. Cui M, Huang Y, Zhao Y, Zheng J. Transcription factor FOXO3a mediates apoptosis in HIV-1-infected macrophages. J Immunol. 2008;180:898-906 pubmed
    ..In the present study, we investigated the involvement of transcription factor FOXO3a in the regulation of HIV-1-mediated apoptosis in macrophages...
  41. Tseng A, Shieh S, Wang D. SIRT3 deacetylates FOXO3 to protect mitochondria against oxidative damage. Free Radic Biol Med. 2013;63:222-34 pubmed publisher
    ..Hence, our finding that SIRT3 deacetylates FOXO3 to protect mitochondria against oxidative stress provides a possible direction for aging-delaying therapies and disease intervention. ..
  42. van der Horst A, de Vries Smits A, Brenkman A, van Triest M, van den Broek N, Colland F, et al. FOXO4 transcriptional activity is regulated by monoubiquitination and USP7/HAUSP. Nat Cell Biol. 2006;8:1064-73 pubmed
    ..Our results demonstrate a novel mechanism of FOXO regulation and indicate that USP7 has an important role in regulating FOXO-mediated stress responses. ..
  43. Shang Y, Chong Z, Hou J, Maiese K. FoxO3a governs early microglial proliferation and employs mitochondrial depolarization with caspase 3, 8, and 9 cleavage during oxidant induced apoptosis. Curr Neurovasc Res. 2009;6:223-38 pubmed
    ..deprivation (OGD) injury model of oxidative stress the role of the "O" class forkhead transcription factor FoxO3a that in some scenarios is closely linked to immune system function...
  44. Lützner N, Kalbacher H, Krones Herzig A, Rösl F. FOXO3 is a glucocorticoid receptor target and regulates LKB1 and its own expression based on cellular AMP levels via a positive autoregulatory loop. PLoS ONE. 2012;7:e42166 pubmed publisher
    ..In conclusion, our data explain how catabolic glucocorticoid hormones and high intracellular AMP levels cooperate in inducing FOXO3 transcription and in activating the corresponding protein. ..
  45. Kops G, Medema R, Glassford J, Essers M, Dijkers P, Coffer P, et al. Control of cell cycle exit and entry by protein kinase B-regulated forkhead transcription factors. Mol Cell Biol. 2002;22:2025-36 pubmed
    ..Here we show that the Forkheads AFX (FOXO4) and FKHR-L1 (FOXO3a) also directly control transcription of the retinoblastoma-like p130 protein and cause upregulation of p130 ..
  46. Luron L, Saliba D, Blazek K, Lanfrancotti A, Udalova I. FOXO3 as a new IKK-?-controlled check-point of regulation of IFN-? expression. Eur J Immunol. 2012;42:1030-7 pubmed publisher
    ..Thus, we identify FOXO3 as a new IKK-?-controlled check-point of IRF activation and regulation of IFN-? expression, providing new insight into the role of FOXO3 in immune response control. ..
  47. Seoane J, Le H, Shen L, Anderson S, Massague J. Integration of Smad and forkhead pathways in the control of neuroepithelial and glioblastoma cell proliferation. Cell. 2004;117:211-23 pubmed
    ..We suggest that the activity of this network confers resistance to TGF-beta-mediated cytostasis during the development of the telencephalic neuroepithelium and in glioblastoma brain tumor cells. ..
  48. Obexer P, Geiger K, Ambros P, Meister B, Ausserlechner M. FKHRL1-mediated expression of Noxa and Bim induces apoptosis via the mitochondria in neuroblastoma cells. Cell Death Differ. 2007;14:534-47 pubmed
    Protein kinase-B (PKB) and its target, the forkhead transcription factor like 1 (FKHRL1)/FoxO3a, have been suggested as regulators of neurotrophin-mediated cell survival in neuronal cells...
  49. Zou Y, Tsai W, Cheng C, Hsu C, Chung Y, Li P, et al. Forkhead box transcription factor FOXO3a suppresses estrogen-dependent breast cancer cell proliferation and tumorigenesis. Breast Cancer Res. 2008;10:R21 pubmed publisher
    ..The forkhead box class O (FOXO) transcription factor FOXO3a has been suggested to function as a tumor suppressor in breast cancer...
  50. Yu C, Zhang Z, Liao W, Zhao X, Liu L, Wu Y, et al. The tumor-suppressor gene Nkx2.8 suppresses bladder cancer proliferation through upregulation of FOXO3a and inhibition of the MEK/ERK signaling pathway. Carcinogenesis. 2012;33:678-86 pubmed publisher
    ..8 resulted in G(1)/S phase arrest, accompanied by upregulation of p27(Kip1), downregulation of cyclin D1 and p-FOXO3a and inhibition of MEK/ERK pathway activity. Meanwhile, silencing Nkx2...
  51. Liu J, Chandra D, Rudd M, Butler A, Pallotta V, Brown D, et al. Induction of prosurvival molecules by apoptotic stimuli: involvement of FOXO3a and ROS. Oncogene. 2005;24:2020-31 pubmed
    ..One master transcription factor, FOXO3a, is involved in the transcriptional activation of some of these prosurvival (e.g., MnSOD) and proapoptotic (e.g...
  52. Jacobs K, Pennington J, Bisht K, Aykin Burns N, Kim H, Mishra M, et al. SIRT3 interacts with the daf-16 homolog FOXO3a in the mitochondria, as well as increases FOXO3a dependent gene expression. Int J Biol Sci. 2008;4:291-9 pubmed
    ..For the first time we establish that FOXO3a is also a mitochondrial protein and forms a physical interaction with SIRT3 in mitochondria...
  53. Segura M, Hanniford D, Menendez S, Reavie L, Zou X, Alvarez Diaz S, et al. Aberrant miR-182 expression promotes melanoma metastasis by repressing FOXO3 and microphthalmia-associated transcription factor. Proc Natl Acad Sci U S A. 2009;106:1814-9 pubmed publisher
    ..Our data provide a mechanism for invasion and survival in melanoma that could prove applicable to metastasis of other cancers and suggest that miRNA silencing may be a worthwhile therapeutic strategy. ..
  54. Obrador Hevia A, Serra Sitjar M, Rodriguez J, Villalonga P, Fernandez De Mattos S. The tumour suppressor FOXO3 is a key regulator of mantle cell lymphoma proliferation and survival. Br J Haematol. 2012;156:334-45 pubmed publisher
    ..Taken together, our results confirm that FOXO3 is a relevant regulator of proliferation and apoptosis in MCL, and suggest that reactivation of FOXO3 function might be a useful therapeutic strategy in MCL patients. ..
  55. Ausserlechner M, Salvador C, Deutschmann A, Bodner M, Viola G, Bortolozzi R, et al. Therapy-resistant acute lymphoblastic leukemia (ALL) cells inactivate FOXO3 to escape apoptosis induction by TRAIL and Noxa. Oncotarget. 2013;4:995-1007 pubmed
    ..This suggests that if p16INK4A is deleted during leukemia development, FOXO3 levels elevate and FOXO3 has to be inactivated by deregulation of the PI3K-PKB pathway to prevent FOXO3-induced cell death. ..
  56. Lee J, Espéli M, Anderson C, Linterman M, Pocock J, Williams N, et al. Human SNP links differential outcomes in inflammatory and infectious disease to a FOXO3-regulated pathway. Cell. 2013;155:57-69 pubmed publisher
    ..We identify a noncoding polymorphism in FOXO3A (rs12212067: T > G) at which the minor (G) allele, despite not being associated with disease susceptibility, is ..
  57. Anderson M, Viars C, Czekay S, Cavenee W, Arden K. Cloning and characterization of three human forkhead genes that comprise an FKHR-like gene subfamily. Genomics. 1998;47:187-99 pubmed
    ..The three genes (HGMW-approved symbols FKHRP1, FKHRL1, and FKHRL1P1) map to chromosomal regions 5q35.2-q35.3, 6q21, and 17p11, respectively...
  58. Mahmud D, G Amlak M, Deb D, Platanias L, Uddin S, Wickrema A. Phosphorylation of forkhead transcription factors by erythropoietin and stem cell factor prevents acetylation and their interaction with coactivator p300 in erythroid progenitor cells. Oncogene. 2002;21:1556-62 pubmed
    The mammalian forkhead transcription factors, FOXO3a (FKHRL1), FOXO1a (FKHR) and FOXO4 (AFX) are negatively regulated by PKB/Akt kinase...
  59. van der Horst A, Tertoolen L, de Vries Smits L, Frye R, Medema R, Burgering B. FOXO4 is acetylated upon peroxide stress and deacetylated by the longevity protein hSir2(SIRT1). J Biol Chem. 2004;279:28873-9 pubmed
    ..These data demonstrate that acetylation functions in a second pathway of negative control for FOXO factors and provides a novel mechanism whereby hSir2(SIRT1) can promote cellular survival and increase lifespan. ..
  60. Jin G, Kondo E, Miyake T, Shibata M, Takashima T, Liu Y, et al. Expression and intracellular localization of FKHRL1 in mammary gland neoplasms. Acta Med Okayama. 2004;58:197-205 pubmed
    FKHRL1 (FOXO3a), a member of the Forkhead family of genes, has been considered to be involved in the development of breast tumors; however, the in vivo expression and activation status of FKHRL1 in breast tumors still remains unclear...
  61. Li Y, Wang W, Cao H, Lu J, Wu C, Hu F, et al. Genetic association of FOXO1A and FOXO3A with longevity trait in Han Chinese populations. Hum Mol Genet. 2009;18:4897-904 pubmed publisher
    FOXO1A and FOXO3A are two members of the FoxO family. FOXO3A has recently been linked to human longevity in Japanese, German and Italian populations...
  62. Chen J, Gomes A, Monteiro L, Wong S, Wu L, Ng T, et al. Constitutively nuclear FOXO3a localization predicts poor survival and promotes Akt phosphorylation in breast cancer. PLoS ONE. 2010;5:e12293 pubmed publisher
    ..The PI3K-Akt signal pathway plays a key role in tumorigenesis and the development of drug-resistance. Cytotoxic chemotherapy resistance is linked to limited therapeutic options and poor prognosis...
  63. Shiota M, Song Y, Yokomizo A, Kiyoshima K, Tada Y, Uchino H, et al. Foxo3a suppression of urothelial cancer invasiveness through Twist1, Y-box-binding protein 1, and E-cadherin regulation. Clin Cancer Res. 2010;16:5654-63 pubmed publisher
    Invasion and metastasis are key steps in the progression of urothelial cancer (UC) into a critical disease. Foxo3a is a member of the Foxo transcription factor family that modulates the expression of various genes...
  64. Lin H, Dai T, Xiong H, Zhao X, Chen X, Yu C, et al. Unregulated miR-96 induces cell proliferation in human breast cancer by downregulating transcriptional factor FOXO3a. PLoS ONE. 2010;5:e15797 pubmed publisher
    ..Moreover, we demonstrated that miR-96 downregulated FOXO3a expression by directly targeting the FOXO3a 3'-untranslated region...
  65. Habashy H, Rakha E, Aleskandarany M, Ahmed M, Green A, Ellis I, et al. FOXO3a nuclear localisation is associated with good prognosis in luminal-like breast cancer. Breast Cancer Res Treat. 2011;129:11-21 pubmed publisher
    ..Recent studies have identified Forkhead box O3a (FOXO3a) transcription factor as an intracellular mediator of ER? expression and as an important downstream ..
  66. Dobson M, Ramakrishnan G, Ma S, Kaplun L, Balan V, Fridman R, et al. Bimodal regulation of FoxO3 by AKT and 14-3-3. Biochim Biophys Acta. 2011;1813:1453-64 pubmed publisher
  67. Ferber E, Peck B, Delpuech O, Bell G, East P, Schulze A. FOXO3a regulates reactive oxygen metabolism by inhibiting mitochondrial gene expression. Cell Death Differ. 2012;19:968-79 pubmed publisher
    ..performed a detailed analysis of the transcriptional programme induced in response to Forkhead-box protein O3a (FOXO3a) activation...
  68. Hagenbuchner J, Kuznetsov A, Hermann M, Hausott B, Obexer P, Ausserlechner M. FOXO3-induced reactive oxygen species are regulated by BCL2L11 (Bim) and SESN3. J Cell Sci. 2012;125:1191-203 pubmed publisher
    ..To identify the sequence of molecular events underlying FOXO3 (FKHRL1)-induced apoptosis, we studied the regulation and function of FOXO3 by expressing an ECFP-tagged FOXO3 or a 4OH-..
  69. Brunet A, Sweeney L, Sturgill J, Chua K, Greer P, Lin Y, et al. Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science. 2004;303:2011-5 pubmed
    ..Thus, one way in which members of the Sir2 family of proteins may increase organismal longevity is by tipping FOXO-dependent responses away from apoptosis and toward stress resistance. ..
  70. Wu W, Zou M, Brickley D, Pew T, Conzen S. Glucocorticoid receptor activation signals through forkhead transcription factor 3a in breast cancer cells. Mol Endocrinol. 2006;20:2304-14 pubmed
    ..We now report that activation of the GR mediates Forkhead transcription factor 3a (FOXO3a) phosphorylation and inactivation in mammary epithelial cells...
  71. Greer E, Oskoui P, Banko M, Maniar J, Gygi M, Gygi S, et al. The energy sensor AMP-activated protein kinase directly regulates the mammalian FOXO3 transcription factor. J Biol Chem. 2007;282:30107-19 pubmed
    ..The regulation of FOXO3 by AMPK may play a crucial role in fine tuning gene expression programs that control energy balance and stress resistance in cells throughout life. ..
  72. Lee H, You H, Won J, Youn S, Cho H, Park K, et al. Forkhead factor, FOXO3a, induces apoptosis of endothelial cells through activation of matrix metalloproteinases. Arterioscler Thromb Vasc Biol. 2008;28:302-8 pubmed
    The forkhead factor, FOXO3a, is known to induce apoptosis in endothelial cells (ECs). However, its effects on extracellular matrices (ECM), which are important in EC survival, remained unknown...
  73. Wildey G, Howe P. Runx1 is a co-activator with FOXO3 to mediate transforming growth factor beta (TGFbeta)-induced Bim transcription in hepatic cells. J Biol Chem. 2009;284:20227-39 pubmed publisher
    ..Our results support a mechanism in which TGFbeta stimulates Bim transcription by up-regulating Runx1 expression, which binds FOXO3, and the two cooperate in the transcriptional induction of Bim. ..
  74. Li X, Song J, Zhang L, LeMaire S, Hou X, Zhang C, et al. Activation of the AMPK-FOXO3 pathway reduces fatty acid-induced increase in intracellular reactive oxygen species by upregulating thioredoxin. Diabetes. 2009;58:2246-57 pubmed publisher
    ..Thus, the AMPK-FOXO3-Trx axis may be an important defense mechanism against excessive ROS production induced by metabolic stress and could be a therapeutic target in treating cardiovascular diseases in metabolic syndrome. ..
  75. Tzivion G, Dobson M, Ramakrishnan G. FoxO transcription factors; Regulation by AKT and 14-3-3 proteins. Biochim Biophys Acta. 2011;1813:1938-45 pubmed publisher
    ..This article is part of a Special Issue entitled: PI3K-AKT-FoxO axis in cancer and aging. ..
  76. Su J, Cheng X, Yamaguchi H, Chang Y, Hou C, Lee D, et al. FOXO3a-Dependent Mechanism of E1A-Induced Chemosensitization. Cancer Res. 2011;71:6878-87 pubmed publisher paclitaxel has been reported to occur in cells expressing low levels of the Forkhead transcription factor FOXO3a. In this article, we report that FOXO3a is critical for E1A-mediated chemosensitization to paclitaxel...
  77. Lu M, Zhao Y, Xu F, Wang Y, Xiang J, Chen D. The expression and prognosis of FOXO3a and Skp2 in human ovarian cancer. Med Oncol. 2012;29:3409-15 pubmed publisher
    ..Recently, ubiquitination and proteasome degradation of FOXO3a have been reported. In this study, we investigated the role of FOXO3a and Skp2 in human ovarian cancer...
  78. Hillion J, Le Coniat M, Jonveaux P, Berger R, Bernard O. AF6q21, a novel partner of the MLL gene in t(6;11)(q21;q23), defines a forkhead transcriptional factor subfamily. Blood. 1997;90:3714-9 pubmed
    ..The novel gene, named AF6q21, encodes a forkhead (FH) protein with strong similarities to the two FH family members whose genes are already ..
  79. Sunters A, Fernandez De Mattos S, Stahl M, Brosens J, Zoumpoulidou G, Saunders C, et al. FoxO3a transcriptional regulation of Bim controls apoptosis in paclitaxel-treated breast cancer cell lines. J Biol Chem. 2003;278:49795-805 pubmed
    ..Western blotting revealed that in a panel of nine breast cancer cell lines expression of FoxO1a and FoxO3a correlated with the expression of the pro-apoptotic FoxO target Bim, which was associated with paclitaxel-induced ..
  80. Jang S, Yang S, Srinivasan S, Ye K. Akt phosphorylates MstI and prevents its proteolytic activation, blocking FOXO3 phosphorylation and nuclear translocation. J Biol Chem. 2007;282:30836-44 pubmed
    ..Thus, our findings support that Akt blocks MstI-triggered FOXO3 nuclear translocation by phosphorylating MstI, promoting cell survival. ..
  81. Chiribau C, Cheng L, Cucoranu I, Yu Y, Clempus R, Sorescu D. FOXO3A regulates peroxiredoxin III expression in human cardiac fibroblasts. J Biol Chem. 2008;283:8211-7 pubmed publisher
    ..Recently the transcription factor FOXO3A has been shown to increase resistance to oxidative stress by up-regulation of mitochondrial superoxide dismutase ..
  82. Khatri S, Yepiskoposyan H, Gallo C, Tandon P, Plas D. FOXO3a regulates glycolysis via transcriptional control of tumor suppressor TSC1. J Biol Chem. 2010;285:15960-5 pubmed publisher
    ..We find that FoxO3a knockdown is sufficient to induce apoptosis resistance in conjunction with elevated glycolysis...
  83. Lam M, Carmichael A, Griffiths H. An aqueous extract of Fagonia cretica induces DNA damage, cell cycle arrest and apoptosis in breast cancer cells via FOXO3a and p53 expression. PLoS ONE. 2012;7:e40152 pubmed publisher
    ..p53-independent growth arrest and cytotoxicity following DNA damage has been previously ascribed to FOXO3a expression...
  84. Santo E, Stroeken P, Sluis P, Koster J, Versteeg R, Westerhout E. FOXO3a is a major target of inactivation by PI3K/AKT signaling in aggressive neuroblastoma. Cancer Res. 2013;73:2189-98 pubmed publisher
    ..Here we identify the forkhead transcription factor FOXO3a as a key target of the PI3K/AKT pathway in neuroblastoma...
  85. Bullock M, Bruce A, Sreekumar R, Curtis N, Cheung T, Reading I, et al. FOXO3 expression during colorectal cancer progression: biomarker potential reflects a tumour suppressor role. Br J Cancer. 2013;109:387-94 pubmed publisher
    ..To clarify its role in human colorectal cancer (CRC) progression, we examined in vivo FOXO3 expression at key points of the metastatic cascade...
  86. Pino E, Amamoto R, Zheng L, Cacquevel M, Sarria J, Knott G, et al. FOXO3 determines the accumulation of ?-synuclein and controls the fate of dopaminergic neurons in the substantia nigra. Hum Mol Genet. 2014;23:1435-52 pubmed publisher
    ..Here, we genetically modulate the activity of the transcription factor Forkhead box protein O3 (FOXO3) in adult nigral dopaminergic neurons using viral vectors and explore how this determinant of ..
  87. Skurk C, Maatz H, Kim H, Yang J, Abid M, Aird W, et al. The Akt-regulated forkhead transcription factor FOXO3a controls endothelial cell viability through modulation of the caspase-8 inhibitor FLIP. J Biol Chem. 2004;279:1513-25 pubmed
    ..Here we examined the role of the forkhead transcription factor FOXO3a, a downstream target of Akt, in controlling FLIP regulation in endothelial cells...
  88. Lehtinen M, Yuan Z, Boag P, Yang Y, Villen J, Becker E, et al. A conserved MST-FOXO signaling pathway mediates oxidative-stress responses and extends life span. Cell. 2006;125:987-1001 pubmed
  89. Li Y, Wang Z, Kong D, Murthy S, Dou Q, Sheng S, et al. Regulation of FOXO3a/beta-catenin/GSK-3beta signaling by 3,3'-diindolylmethane contributes to inhibition of cell proliferation and induction of apoptosis in prostate cancer cells. J Biol Chem. 2007;282:21542-50 pubmed
    ..It has been known that FOXO3a and glycogen synthase kinase-3beta (GSK-3beta), two targets of activated Akt, interact with beta-catenin, ..
  90. Chiacchiera F, Simone C. The AMPK-FoxO3A axis as a target for cancer treatment. Cell Cycle. 2010;9:1091-6 pubmed
    ..The transcriptional activity of FoxO3A, one of the four members of the family, is further modulated by AMPK, one of the key regulators of cellular ..
  91. Zeng Y, Cheng L, Chen H, Cao H, Hauser E, Liu Y, et al. Effects of FOXO genotypes on longevity: a biodemographic analysis. J Gerontol A Biol Sci Med Sci. 2010;65:1285-99 pubmed publisher
    ..We also estimate independent and joint effects of the genotypes of FOXO1A and FOXO3A genes on long-term survival, considering carrying or not-carrying the minor allele of the single-nucleotide ..
  92. Chen S, Gai J, Wang Y, Li H. FoxO regulates expression of decidual protein induced by progesterone (DEPP) in human endothelial cells. FEBS Lett. 2011;585:1796-800 pubmed publisher
    ..hy926. Hypoxia-induced upregulation of DEPP is dependent on FoxO expression. We conclude that DEPP is regulated at the level of transcription by FoxO in human vascular endothelial cells. ..