FKHRL1

Summary

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

Top Publications

  1. ncbi Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor
    A Brunet
    Children s Hospital and Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cell 96:857-68. 1999
  2. ncbi Nutrient availability regulates SIRT1 through a forkhead-dependent pathway
    Shino Nemoto
    Cardiovascular Branch, National Heart, Lung, and Blood Institute NHLBI, Bethesda, MD 20892, USA
    Science 306:2105-8. 2004
  3. ncbi The energy sensor AMP-activated protein kinase directly regulates the mammalian FOXO3 transcription factor
    Eric L Greer
    Department of Genetics, Stanford University, Stanford, California 94305, USA
    J Biol Chem 282:30107-19. 2007
  4. pmc Forkhead box transcription factor FOXO3a suppresses estrogen-dependent breast cancer cell proliferation and tumorigenesis
    Yiyu Zou
    Department of Medicine, Albert Einstein College of Medicine, East 210th Street, Bronx, New York, New York 10467, USA
    Breast Cancer Res 10:R21. 2008
  5. pmc Tat-induced FOXO3a is a key mediator of apoptosis in HIV-1-infected human CD4+ T lymphocytes
    Alicja Dabrowska
    Department of Medicine, Children s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 181:8460-77. 2008
  6. ncbi 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
    Hae Young Lee
    National Research Laboratory for Cardiovascular Stem Cell, Seoul National University Hospital, Korea
    Circ Res 100:372-80. 2007
  7. ncbi Cloning and characterization of three human forkhead genes that comprise an FKHR-like gene subfamily
    M J Anderson
    Ludwig Institute for Cancer Research, San Diego Branch, California, USA
    Genomics 47:187-99. 1998
  8. pmc Methylation by Set9 modulates FoxO3 stability and transcriptional activity
    DANIEL R CALNAN
    Cancer Biology Program, Stanford University, CA 94305, USA
    Aging (Albany NY) 4:462-79. 2012
  9. pmc FoxO3a (Forkhead Box O3a) deficiency protects Idiopathic Pulmonary Fibrosis (IPF) fibroblasts from type I polymerized collagen matrix-induced apoptosis via caveolin-1 (cav-1) and Fas
    Richard Seonghun Nho
    Department of Medicine, University of Minnesota, Minneapolis, Minnesota, United States of America
    PLoS ONE 8:e61017. 2013
  10. ncbi Neutrophil activation by fMLP regulates FOXO (forkhead) transcription factors by multiple pathways, one of which includes the binding of FOXO to the survival factor Mcl-1
    Lisa J Crossley
    Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Leukoc Biol 74:583-92. 2003

Research Grants

  1. Saghi Ghaffari; Fiscal Year: 2015
  2. Steven A Weinman; Fiscal Year: 2016
  3. AKT Signaling and Oxidative Stress Regulation of Erythropoiesis
    Saghi Ghaffari; Fiscal Year: 2013
  4. Insulin Signaling and the Heart in Diabetes
    EVAN DALE ABEL; Fiscal Year: 2011
  5. Novel Strategies for Treatment of Myeloproliferative Disorders
    Roya Khosravi-Far; Fiscal Year: 2012
  6. MARIA JOSE ALMEIDA; Fiscal Year: 2016
  7. The role of the deacetylase Sirt1 in the maintenance of adult neural stem cells
    VICTORIA RAFALSKI; Fiscal Year: 2010
  8. Qishen Pang; Fiscal Year: 2014
  9. Mitchell Kronenberg; Fiscal Year: 2014
  10. Jonathan S Weissman; Fiscal Year: 2016

Detail Information

Publications235 found, 100 shown here

  1. ncbi Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor
    A Brunet
    Children s Hospital and Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cell 96:857-68. 1999
    ..In this study, we demonstrate that Akt also regulates the activity of FKHRL1, a member of the Forkhead family of transcription factors...
  2. ncbi Nutrient availability regulates SIRT1 through a forkhead-dependent pathway
    Shino Nemoto
    Cardiovascular Branch, National Heart, Lung, and Blood Institute NHLBI, Bethesda, MD 20892, USA
    Science 306:2105-8. 2004
    ..simultaneously augments expression of the SIRT1 deacetylase and activates the Forkhead transcription factor Foxo3a. Knockdown of Foxo3a expression inhibited the starvation-induced increase in SIRT1 expression...
  3. ncbi The energy sensor AMP-activated protein kinase directly regulates the mammalian FOXO3 transcription factor
    Eric L Greer
    Department of Genetics, Stanford University, Stanford, California 94305, USA
    J Biol Chem 282:30107-19. 2007
    ..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...
  4. pmc Forkhead box transcription factor FOXO3a suppresses estrogen-dependent breast cancer cell proliferation and tumorigenesis
    Yiyu Zou
    Department of Medicine, Albert Einstein College of Medicine, East 210th Street, Bronx, New York, New York 10467, USA
    Breast Cancer Res 10:R21. 2008
    ..The forkhead box class O (FOXO) transcription factor FOXO3a has been suggested to function as a tumor suppressor in breast cancer...
  5. pmc Tat-induced FOXO3a is a key mediator of apoptosis in HIV-1-infected human CD4+ T lymphocytes
    Alicja Dabrowska
    Department of Medicine, Children s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 181:8460-77. 2008
    ..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...
  6. ncbi 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
    Hae Young Lee
    National Research Laboratory for Cardiovascular Stem Cell, Seoul National University Hospital, Korea
    Circ Res 100:372-80. 2007
    ..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 ..
  7. ncbi Cloning and characterization of three human forkhead genes that comprise an FKHR-like gene subfamily
    M J Anderson
    Ludwig Institute for Cancer Research, San Diego Branch, California, USA
    Genomics 47:187-99. 1998
    ..The three genes (HGMW-approved symbols FKHRP1, FKHRL1, and FKHRL1P1) map to chromosomal regions 5q35.2-q35.3, 6q21, and 17p11, respectively...
  8. pmc Methylation by Set9 modulates FoxO3 stability and transcriptional activity
    DANIEL R CALNAN
    Cancer Biology Program, Stanford University, CA 94305, USA
    Aging (Albany NY) 4:462-79. 2012
    ..The modulation of FoxO3 stability and activity by methylation may be critical for fine-tuning cellular responses to stress stimuli, which may in turn affect FoxO3's ability to promote tumor suppression and longevity...
  9. pmc FoxO3a (Forkhead Box O3a) deficiency protects Idiopathic Pulmonary Fibrosis (IPF) fibroblasts from type I polymerized collagen matrix-induced apoptosis via caveolin-1 (cav-1) and Fas
    Richard Seonghun Nho
    Department of Medicine, University of Minnesota, Minneapolis, Minnesota, United States of America
    PLoS ONE 8:e61017. 2013
    ..We have previously found that FoxO3a, a transcriptional activator of apoptosis-inducing proteins, is inactivated in IPF fibroblasts resulting from ..
  10. ncbi Neutrophil activation by fMLP regulates FOXO (forkhead) transcription factors by multiple pathways, one of which includes the binding of FOXO to the survival factor Mcl-1
    Lisa J Crossley
    Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Leukoc Biol 74:583-92. 2003
    ..These studies show that fMLP-stimulated neutrophils coordinate the regulation of FOXO transcription factors and the survival factor Mcl-1, a mechanism that may allow neutrophils to alter their survival...
  11. pmc Vitamin D3 up-regulated protein 1(VDUP1) is regulated by FOXO3A and miR-17-5p at the transcriptional and post-transcriptional levels, respectively, in senescent fibroblasts
    De Xiang Zhuo
    Department of Biochemistry and Molecular Biology, Health Science Center, Peking University, 100191 Beijing, China
    J Biol Chem 285:31491-501. 2010
    ..Subsequently, we found that FOXO3A, whose activity increased in senescent cells, transcriptionally up-regulates VDUP1 expression and miR-17-5p, whose ..
  12. ncbi FoxO3a transcriptional regulation of Bim controls apoptosis in paclitaxel-treated breast cancer cell lines
    Andrew Sunters
    Cancer Research UK Laboratories, Department of Cancer Medicine, Medical Research Council Cyclotron Building, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom
    J Biol Chem 278:49795-805. 2003
    ..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 ..
  13. ncbi Direct transcriptional regulation of Bim by FoxO3a mediates STI571-induced apoptosis in Bcr-Abl-expressing cells
    Abdelkader Essafi
    Cancer Research UK Labs, Department of Cancer Medicine, MRC Cyclotron Building, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK
    Oncogene 24:2317-29. 2005
    ..BaF3/Bcr-Abl-expressing cell lines as model systems to investigate the molecular mechanisms whereby STI571 and FoxO3a regulate Bim expression and apoptosis...
  14. doi Wnt signaling inhibits Forkhead box O3a-induced transcription and apoptosis through up-regulation of serum- and glucocorticoid-inducible kinase 1
    Manuel Dehner
    Department of Experimental Medicine II, Nikolaus Fiebiger Center for Molecular Medicine, University of Erlangen, Glueckstrasse 6, 91054 Erlangen, Germany
    J Biol Chem 283:19201-10. 2008
    ..SGK1 negatively regulates the pro-apoptotic transcription factor Forkhead box O3a (FoxO3a) via phosphorylation and exclusion from the nucleus...
  15. pmc Runx1 is a co-activator with FOXO3 to mediate transforming growth factor beta (TGFbeta)-induced Bim transcription in hepatic cells
    Gary M Wildey
    Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Biol Chem 284:20227-39. 2009
    ..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...
  16. doi Expression and prognosis of FOXO3a and HIF-1α in nasopharyngeal carcinoma
    Zhu Shou
    Department of Otolaryngology, The First Affiliated Hospital of Chongqing Medical University, No 1 Youyi Road, Chongqing 400016, People s Republic of China
    J Cancer Res Clin Oncol 138:585-93. 2012
    The Forkhead Box O3a transcription factor (FOXO3a) and hypoxia-inducible factor-1α (HIF-1α) have been reported to play important roles in the development and prognosis of human cancers. However, their exact roles are not clear...
  17. doi Atrogin-1, MuRF1, and FoXO, as well as phosphorylated GSK-3beta and 4E-BP1 are reduced in skeletal muscle of chronic spinal cord-injured patients
    Bertrand Leger
    Institut de Recherche en Réadaptation Réinsertion, Sion, Switzerland
    Muscle Nerve 40:69-78. 2009
    ..05), and myostatin (46%; P < 0.01), and in protein levels of FoXO1 (72%; P < 0.05), FoXO3a (60%; P < 0.05), and atrogin-1 (36%; P < 0.05). Decreases in the protein levels of IGF-1 (48%; P < 0...
  18. ncbi The Akt-regulated forkhead transcription factor FOXO3a controls endothelial cell viability through modulation of the caspase-8 inhibitor FLIP
    Carsten Skurk
    Molecular Cardiology Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts 02118, USA
    J Biol Chem 279:1513-25. 2004
    ..Here we examined the role of the forkhead transcription factor FOXO3a, a downstream target of Akt, in controlling FLIP regulation in endothelial cells...
  19. pmc ERK promotes tumorigenesis by inhibiting FOXO3a via MDM2-mediated degradation
    Jer Yen Yang
    Department of Molecular and Cellular Oncology, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Nat Cell Biol 10:138-48. 2008
    ..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 ..
  20. pmc Insulin acts through FOXO3a to activate transcription of plasminogen activator inhibitor type 1
    Ushma R Jag
    Department of Pharmacology, New York University School of Medicine, New York, New York 10016, USA
    Mol Endocrinol 23:1587-602. 2009
    ..Here we demonstrate that overexpression of Forkhead-related transcription factor (Fox)O1, FoxO3a, and FoxC1 augment insulin's ability to activate the PAI-1 promoter...
  21. ncbi Human immunodeficiency virus type-1 accessory protein Vpr: a causative agent of the AIDS-related insulin resistance/lipodystrophy syndrome?
    Tomoshige Kino
    Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892 1583, USA
    Ann N Y Acad Sci 1024:153-67. 2004
    ....
  22. ncbi Akt phosphorylates MstI and prevents its proteolytic activation, blocking FOXO3 phosphorylation and nuclear translocation
    Sung Wuk Jang
    Department of Pathology, Division of Digestive Diseases, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    J Biol Chem 282:30836-44. 2007
    ..Thus, our findings support that Akt blocks MstI-triggered FOXO3 nuclear translocation by phosphorylating MstI, promoting cell survival...
  23. pmc FOXO3a regulates glycolysis via transcriptional control of tumor suppressor TSC1
    Shikha Khatri
    Department of Cancer and Cell Biology, University of Cincinnati, Cincinnati, Ohio 45267, USA
    J Biol Chem 285:15960-5. 2010
    ..We find that FoxO3a knockdown is sufficient to induce apoptosis resistance in conjunction with elevated glycolysis...
  24. pmc Constitutively nuclear FOXO3a localization predicts poor survival and promotes Akt phosphorylation in breast cancer
    Jie Chen
    Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
    PLoS ONE 5:e12293. 2010
    ..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...
  25. pmc FoxO3a and BCR-ABL regulate cyclin D2 transcription through a STAT5/BCL6-dependent mechanism
    Silvia Fernandez De Mattos
    Cancer Research UK Laboratories, Department of Cancer Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom
    Mol Cell Biol 24:10058-71. 2004
    ..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...
  26. ncbi HIV-1 accessory protein Vpr inhibits the effect of insulin on the Foxo subfamily of forkhead transcription factors by interfering with their binding to 14-3-3 proteins: potential clinical implications regarding the insulin resistance of HIV-1-infected pat
    Tomoshige Kino
    Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Development, NIH, 10 Center Dr MSC 1109, Building 10, Clinical Research Center, Room 1 3140, Bethesda, MD 20892 1109, USA
    Diabetes 54:23-31. 2005
    ..we report that the same viral protein interfered with and altered the activity of another 14-3-3 partner molecule, Foxo3a, a subtype of the forkhead transcription factors, by inhibiting its association with 14-3-3...
  27. pmc Vpr protein of human immunodeficiency virus type 1 binds to 14-3-3 proteins and facilitates complex formation with Cdc25C: implications for cell cycle arrest
    Tomoshige Kino
    Human Retrovirus Section, Center for Cancer Research, National Cancer Institute Frederick, Bldg 535, Rm 210, Frederick, MD 21702 1201, USA
    J Virol 79:2780-7. 2005
    ..These results indicate that Vpr promotes cell cycle arrest at the G(2)/M phase by facilitating association of 14-3-3 and Cdc25C independently of the latter's phosphorylation status...
  28. doi A cross-talk between stromal cell-derived factor-1 and transforming growth factor-beta controls the quiescence/cycling switch of CD34(+) progenitors through FoxO3 and mammalian target of rapamycin
    Aurélie Chabanon
    Institut National de la Sante et de la Recherche Medicale, Villejuif, France
    Stem Cells 26:3150-61. 2008
    ..We demonstrated a pivotal role of two downstream effectors of the PI3K/Akt pathway, FoxO3a and mammalian target of rapamycin, as connectors in the SDF-1-/TGF-beta-induced control of the cycling/quiescence ..
  29. doi Biochemical and structural characterization of an intramolecular interaction in FOXO3a and its binding with p53
    Feng Wang
    Division of Signaling Biology, Ontario Cancer Institute, Toronto, Ontario, Canada M5G 2M9
    J Mol Biol 384:590-603. 2008
    b>FOXO3a, a forkhead transcription factor and member of the forkhead box class O (FOXO) subfamily, has been shown to promote the translocation of p53 to the cytoplasm, thereby inducing the mitochondria-associated apoptotic pathway...
  30. pmc Muscle-specific f-box only proteins facilitate bk channel β(1) subunit downregulation in vascular smooth muscle cells of diabetes mellitus
    Dai Min Zhang
    Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA
    Circ Res 107:1454-9. 2010
    ..The ubiquitin-proteasome system (UPS) is a major mechanism of intracellular protein degradation. Whether UPS participates in BK-β(1) downregulation in diabetic vessels is unknown...
  31. doi Transcription factor FOXO3a controls the persistence of memory CD4(+) T cells during HIV infection
    Julien van Grevenynghe
    Laboratoire d Immunologie, Centre de Recherche, Hopital Saint Luc, Centre Hospitalier de l Universite de Montreal, 264 Boulevard Rene Levesque Est, Montreal, Quebec H2X 1P1, Canada
    Nat Med 14:266-74. 2008
    ..We show that persistence of T(CM) cells from EC subjects is a direct consequence of inactivation of the FOXO3a pathway...
  32. ncbi AGE-receptor-1 counteracts cellular oxidant stress induced by AGEs via negative regulation of p66shc-dependent FKHRL1 phosphorylation
    Weijing Cai
    Division of Diabetes and Aging Research, The Brookdale Department of Geriatrics, Mount Sinai School of Medicine, New York, NY 10019, USA
    Am J Physiol Cell Physiol 294:C145-52. 2008
    ..Akt, FKHRL1, and antioxidants; e.g., MnSOD, regulate OS. Serine phosphorylation of p66(shc) also promotes OS...
  33. pmc Glucocorticoid (GC)-mediated down-regulation of urokinase plasminogen activator expression via the serum and GC regulated kinase-1/forkhead box O3a pathway
    Travis Pew
    Department of Medicine and Committee on Cancer Biology, University of Chicago, 5841 South Maryland Avenue, MC 2115, Chicago, Illinois 60637, USA
    Endocrinology 149:2637-45. 2008
    ..down-regulate specific genes via serum and glucocorticoid (GC) regulated kinase-1-mediated inhibition of forkhead box O3a (FOXO3a) transcriptional activity...
  34. pmc Epstein-Barr virus latent membrane protein 1 represses DNA repair through the PI3K/Akt/FOXO3a pathway in human epithelial cells
    Yi Ren Chen
    Graduate Institute of Microbiology, College of Medicine, National Taiwan University, 7F, No 1, Section 1, Ren Ai Road, Taipei City 10051, Taiwan
    J Virol 82:8124-37. 2008
    ..Through the LMP1/PI3K/Akt pathway, FOXO3a, which can induce DNA repair, is inactivated because of phosphorylation and relocalization...
  35. pmc Protein kinase SGK mediates survival signals by phosphorylating the forkhead transcription factor FKHRL1 (FOXO3a)
    A Brunet
    Division of Neuroscience, Children s Hospital and Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell Biol 21:952-65. 2001
    ..Akt phosphorylates Forkhead transcription factors such as FKHRL1, leading to FKHRL1's exit from the nucleus and the consequent shutoff of FKHRL1 target genes...
  36. ncbi FOXO proteins regulate tumor necrosis factor-related apoptosis inducing ligand expression. Implications for PTEN mutation in prostate cancer
    Vijayanand Modur
    Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 277:47928-37. 2002
    ..3-kinase pathway and a resultant loss of activity of the FOXO family of forkhead transcription factors FKHRL1 and FKHR...
  37. ncbi Protein kinase B-alpha inhibits human pyruvate dehydrogenase kinase-4 gene induction by dexamethasone through inactivation of FOXO transcription factors
    Hye Sook Kwon
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
    Diabetes 53:899-910. 2004
    ..dexamethasone stimulation of hPDK4 promoter activity, while coexpression of constitutively active FOXO1a or FOXO3a, which are mutated to alanine at the three phosphorylation sites for protein kinase B (PKB), disrupts the ability ..
  38. ncbi Integration of Smad and forkhead pathways in the control of neuroepithelial and glioblastoma cell proliferation
    Joan Seoane
    Cancer Biology and Genetics Program and Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, 1300 York Avenue, New York, NY 1002, USA
    Cell 117:211-23. 2004
    ..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...
  39. ncbi IkappaB kinase promotes tumorigenesis through inhibition of forkhead FOXO3a
    Mickey C T Hu
    Department of Molecular and Cellular Oncology, The University of Texas, Houston, TX 77030, USA
    Cell 117:225-37. 2004
    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...
  40. ncbi The progression of LNCaP human prostate cancer cells to androgen independence involves decreased FOXO3a expression and reduced p27KIP1 promoter transactivation
    Rebecca L Lynch
    Lilly Research Labs, Cancer Division, Eli Lilly and Company, Lilly Corporate Center, Drop Code 0546, Indianapolis, IN 46285, USA
    Mol Cancer Res 3:163-9. 2005
    ..The FOXO3a protein, the most highly expressed FOXO family member in prostate cancer cells, is hyperphosphorylated in LNAI ..
  41. pmc Crystal structure of the human FOXO3a-DBD/DNA complex suggests the effects of post-translational modification
    Kuang Lei Tsai
    Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan
    Nucleic Acids Res 35:6984-94. 2007
    b>FOXO3a is a transcription factor of the FOXO family...
  42. pmc FOXO3A regulates peroxiredoxin III expression in human cardiac fibroblasts
    Calin B Chiribau
    Department of Medicine, Division of Cardiology, Emory University, Atlanta, GA 30322, USA
    J Biol Chem 283:8211-7. 2008
    ..Recently the transcription factor FOXO3A has been shown to increase resistance to oxidative stress by up-regulation of mitochondrial superoxide dismutase ..
  43. doi FOXO3a mediates the androgen-dependent regulation of FLIP and contributes to TRAIL-induced apoptosis of LNCaP cells
    A N Cornforth
    Department of Pathology and Laboratory Medicine, University of California, Irvine, CA 92697 4800, USA
    Oncogene 27:4422-33. 2008
    ..treatment of LNCaP cells with LY294002, or expression of either PTEN or a non-phosphorylatable form of FOXO3a (FOXO3aTM), downregulates FLIP protein and mRNA...
  44. pmc FOXO3A genotype is strongly associated with human longevity
    Bradley J Willcox
    Pacific Health Research Institute, 846 South Hotel Street, Honolulu, HI 96813, USA
    Proc Natl Acad Sci U S A 105:13987-92. 2008
    ..Genetic variation within the FOXO3A gene was strongly associated with human longevity. The OR for homozygous minor vs...
  45. pmc Transcriptional regulation of Bim by FOXO3a and Akt mediates scleroderma serum-induced apoptosis in endothelial progenitor cells
    Shoukang Zhu
    Department of Medicine, University of Miami, Miami, FL 33136, USA
    Circulation 118:2156-65. 2008
    ..We aimed to determine whether circulating EPCs were reduced in scleroderma, whether scleroderma sera could induce EPC apoptosis, and, if so, what the underlying apoptotic signaling pathway was...
  46. pmc Deregulation of FOXO3A during prostate cancer progression
    Sanjeev Shukla
    Department of Urology, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, OH 44106, USA
    Int J Oncol 34:1613-20. 2009
    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...
  47. pmc Activation of the AMPK-FOXO3 pathway reduces fatty acid-induced increase in intracellular reactive oxygen species by upregulating thioredoxin
    Xiao Nan Li
    Division of Cardiothoracic Surgery, Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, USA
    Diabetes 58:2246-57. 2009
    ..The thioredoxin (Trx) system is a major antioxidant system. In this study, we investigated the mechanisms involved in the AMPK-mediated regulation of Trx expression and the reduction of intracellular ROS levels...
  48. pmc Genetic association of FOXO1A and FOXO3A with longevity trait in Han Chinese populations
    Yang Li
    Department of Human Population Genetics, Institute of Molecular Medicine, Peking University, Beijing, China
    Hum Mol Genet 18:4897-904. 2009
    FOXO1A and FOXO3A are two members of the FoxO family. FOXO3A has recently been linked to human longevity in Japanese, German and Italian populations...
  49. pmc MicroRNA-155 regulates cell survival, growth, and chemosensitivity by targeting FOXO3a in breast cancer
    William Kong
    Department of Molecular Oncology, H Lee Moffitt Cancer Center, Tampa, Florida 33612, USA
    J Biol Chem 285:17869-79. 2010
    ..the critical role of miR-155 in regulation of cell survival and chemosensitivity through down-regulation of FOXO3a in breast cancer...
  50. pmc Foxo3a regulates apoptosis by negatively targeting miR-21
    Kun Wang
    Cancer Research Group, National Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
    J Biol Chem 285:16958-66. 2010
    ..Here we report that the transcriptional factor Foxo3a initiates apoptosis by transcriptionally repressing miR-21 expression...
  51. doi Genetic variation in insulin/IGF-1 signaling pathways and longevity
    Elad Ziv
    Department of Medicine, Institute for Human Genetics, Helen Diller Comprehensive Cancer Center, University of California, San Francisco, 94143 3116, United States
    Ageing Res Rev 10:201-4. 2011
    ..One gene, FOXO3A, a transcriptional factor homologous to daf-16, has been repeatedly associated with increased lifespan in several ..
  52. doi The FOXO3A rs2802292 G-allele associates with improved peripheral and hepatic insulin sensitivity and increased skeletal muscle-FOXO3A mRNA expression in twins
    Karina Banasik
    Hagedorn Research Institute, Gentofte, Copenhagen, Denmark
    J Clin Endocrinol Metab 96:E119-24. 2011
    The minor G-allele of FOXO3A rs2802292 has been associated with longevity...
  53. pmc Unregulated miR-96 induces cell proliferation in human breast cancer by downregulating transcriptional factor FOXO3a
    Huanxin Lin
    State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Cancer Center, Sun Yat Sen University, Guangzhou, China
    PLoS ONE 5:e15797. 2010
    ..Moreover, we demonstrated that miR-96 downregulated FOXO3a expression by directly targeting the FOXO3a 3'-untranslated region...
  54. pmc FOXO3 programs tumor-associated DCs to become tolerogenic in human and murine prostate cancer
    Stephanie K Watkins
    Tumor Immunity and Tolerance Section, Laboratory of Molecular Immunoregulation, National Cancer Institute Frederick, Frederick, Maryland 21702, USA
    J Clin Invest 121:1361-72. 2011
    ..Moreover, our results identify what we believe to be a novel target for preventing CTL tolerance and enhancing immune responses to cancer by modulating the immunosuppressive activity of TADCs found in the tumor microenvironment...
  55. doi The expression and significance of pThr32-FOXO3a in human ovarian cancer
    Mudan Lu
    Daozhen Chen, Genetic Laboratory, Wuxi Maternal and Child Health Hospital, The Affiliated Hospital of Nanjing Midical University, 48 Huaishu xiang, 214002 Wuxi, Jiangsu, People s Republic of China
    Med Oncol 29:1258-64. 2012
    b>FOXO3a possesses a large series function, including cellular proliferation, transformation, differentiation, and longevity...
  56. doi FoxO regulates expression of decidual protein induced by progesterone (DEPP) in human endothelial cells
    Simin Chen
    Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Pathophysiology, Nanjing Medical University, Nanjing, China
    FEBS Lett 585:1796-800. 2011
    ..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...
  57. pmc FOXO3 gene variants and human aging: coding variants may not be key players
    Timothy A Donlon
    Honolulu Heart Program, Kuakini Medical Center, Honolulu Hawaii, USA
    J Gerontol A Biol Sci Med Sci 67:1132-9. 2012
    ..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...
  58. ncbi AF6q21, a novel partner of the MLL gene in t(6;11)(q21;q23), defines a forkhead transcriptional factor subfamily
    J Hillion
    Unité Institut National de la Santé et de la Recherche Médicale INSERM U301 and Structure d Intervention SD 401 No 301 Centre National de la Recherche Scientifique CNRS, Institut de Genetique Moleculaire, Paris, France
    Blood 90:3714-9. 1997
    ..The novel gene, named AF6q21, encodes a forkhead (FH) protein with strong similarities to the two FH family members whose genes are already ..
  59. ncbi Ligand-dependent interaction of estrogen receptor-alpha with members of the forkhead transcription factor family
    E R Schuur
    Department of Surgery and Molecular Pharmacology, Stanford University School of Medicine, Stanford, California 94305, USA
    J Biol Chem 276:33554-60. 2001
    ..The related family members, FKHRL1 and AFX, also bound to ER alpha in the presence of beta-estradiol...
  60. pmc Control of cell cycle exit and entry by protein kinase B-regulated forkhead transcription factors
    Geert J P L Kops
    Department of Physiological Chemistry, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands
    Mol Cell Biol 22:2025-36. 2002
    ..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 ..
  61. pmc FoxO3a regulates erythroid differentiation and induces BTG1, an activator of protein arginine methyl transferase 1
    Walbert J Bakker
    Dept of Hematology, Erasmus MC, PO Box 1738, 3000 DR Rotterdam, Netherlands
    J Cell Biol 164:175-84. 2004
    ..b>FoxO3a expression and nuclear accumulation increased during erythroid differentiation, whereas untimely induction of ..
  62. ncbi Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase
    Anne Brunet
    Division of Neuroscience, Children s Hospital, and Department of Neurobiology, Center for Blood Research CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115, USA
    Science 303:2011-5. 2004
    ..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...
  63. ncbi FOXO4 is acetylated upon peroxide stress and deacetylated by the longevity protein hSir2(SIRT1)
    Armando van der Horst
    Department of Physiological Chemistry, Center for Biomedical Genetics, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands
    J Biol Chem 279:28873-9. 2004
    ..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...
  64. ncbi Regulation of FOXO3a by brain-derived neurotrophic factor in differentiated human SH-SY5Y neuroblastoma cells
    Wawa Zhu
    Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, 1075 Sparks Center, 1720 7th Avenue South Birmingham, AL 35294 0017, USA
    Brain Res Mol Brain Res 126:45-56. 2004
    b>FOXO3a is a ubiquitously expressed mammalian forkhead transcription factor with a high expression level in adult brain...
  65. ncbi Functional interaction between beta-catenin and FOXO in oxidative stress signaling
    Marieke A G Essers
    Department of Physiological Chemistry and Center for Biomedical Genetics, University Medical Center, Universiteitsweg 100, 3584 CG Utrecht, Netherlands
    Science 308:1181-4. 2005
    ..These results demonstrate a role for beta-catenin in regulating FOXO function that is particularly important under conditions of oxidative stress...
  66. pmc Involvement of Foxo transcription factors in angiogenesis and postnatal neovascularization
    Michael Potente
    Molecular Cardiology, Department of Internal Medicine III, University of Frankfurt, Frankfurt am Main, Germany
    J Clin Invest 115:2382-92. 2005
    ..Here, we show that Foxo1 and Foxo3a are the most abundant Foxo isoforms in mature endothelial cells and that overexpression of constitutively active ..
  67. ncbi Glucocorticoid receptor activation signals through forkhead transcription factor 3a in breast cancer cells
    Wei Wu
    Department of Medicine and Committee on Cancer Biology, MC 2115, University of Chicago, Chicago, Illinois 60637, USA
    Mol Endocrinol 20:2304-14. 2006
    ..We now report that activation of the GR mediates Forkhead transcription factor 3a (FOXO3a) phosphorylation and inactivation in mammary epithelial cells...
  68. ncbi A conserved MST-FOXO signaling pathway mediates oxidative-stress responses and extends life span
    Maria K Lehtinen
    Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Cell 125:987-1001. 2006
    ....
  69. ncbi FKHRL1-mediated expression of Noxa and Bim induces apoptosis via the mitochondria in neuroblastoma cells
    P Obexer
    Tyrolean Cancer Research Institute, Innsbruck, Austria
    Cell Death Differ 14:534-47. 2007
    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...
  70. pmc Induction of Mxi1-SR alpha by FOXO3a contributes to repression of Myc-dependent gene expression
    Oona Delpuech
    Gene Expression Analysis Laboratory, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3PX, United Kingdom
    Mol Cell Biol 27:4917-30. 2007
    ..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...
  71. ncbi 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
    Yiwei Li
    Department of Pathology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan 48201, USA
    J Biol Chem 282:21542-50. 2007
    ..It has been known that FOXO3a and glycogen synthase kinase-3beta (GSK-3beta), two targets of activated Akt, interact with beta-catenin, ..
  72. ncbi Active FKHRL1 overcomes imatinib resistance in chronic myelogenous leukemia-derived cell lines via the production of tumor necrosis factor-related apoptosis-inducing ligand
    Satoru Kikuchi
    Division of Hematology, Department of Medicine, Jichi Medical University, Tochigi Ken 329 0498, Japan
    Cancer Sci 98:1949-58. 2007
    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 (..
  73. ncbi FOXO3a turns the tumor necrosis factor receptor signaling towards apoptosis through reciprocal regulation of c-Jun N-terminal kinase and NF-kappaB
    Hae Young Lee
    Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Korea
    Arterioscler Thromb Vasc Biol 28:112-20. 2008
    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.
  74. pmc Functional interaction between FOXO3a and ATM regulates DNA damage response
    Wen Bin Tsai
    Department of Molecular Oncology, University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Nat Cell Biol 10:460-7. 2008
    ..Here, we show that FOXO3a interacts with ATM to promote phosphorylation of ATM at Ser 1981 and prompting its downstream mediators to form ..
  75. pmc Foxo3a inhibits cardiomyocyte hypertrophy through transactivating catalase
    Wei Qi Tan
    Division of Cardiovascular Research, National Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
    J Biol Chem 283:29730-9. 2008
    The forkhead transcription factor Foxo3a is able to inhibit cardiomyocyte hypertrophy. However, its underlying molecular mechanism remains to be fully understood...
  76. pmc Association of FOXO3A variation with human longevity confirmed in German centenarians
    Friederike Flachsbart
    Institute of Clinical Molecular Biology, Institute of Medical Informatics and Statistics, and Popgen Biobank, Christian Albrechts University, 24105 Kiel, Germany
    Proc Natl Acad Sci U S A 106:2700-5. 2009
    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...
  77. pmc Repression of BIRC5/survivin by FOXO3/FKHRL1 sensitizes human neuroblastoma cells to DNA damage-induced apoptosis
    Petra Obexer
    Tyrolean Cancer Research Institute, A 6020 Innsbruck, Austria
    Mol Biol Cell 20:2041-8. 2009
    ..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...
  78. pmc MDM2 acts downstream of p53 as an E3 ligase to promote FOXO ubiquitination and degradation
    Wei Fu
    Department of Pathology and Cell Biology, University of South Florida College of Medicine, Tampa, Florida 33612, USA
    J Biol Chem 284:13987-4000. 2009
    ..We show that MDM2 binds to FOXO1 and FOXO3A and promotes their ubiquitination and degradation, a process apparently dependent on FOXO phosphorylation at AKT ..
  79. doi Association of the FOXO3A locus with extreme longevity in a southern Italian centenarian study
    Chiara Viviani Anselmi
    Unit of Genetics and Cardiovascular Research Institute, Istituto Ricovero Cura Carattere Scientifico Multimedica, Sesto S Giovanni, Italy
    Rejuvenation Res 12:95-104. 2009
    ..Recently, several studies suggested that FOXO3A functions as a key bridge for various signaling pathways that influence aging and longevity...
  80. pmc FOXO3a promotes tumor cell invasion through the induction of matrix metalloproteinases
    Peter Storz
    Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Griffin Building, Jacksonville, FL 32224, USA
    Mol Cell Biol 29:4906-17. 2009
    The role of the Forkhead transcription factor FOXO3a in processes that promote tumor metastasis is poorly defined...
  81. pmc FoxO3a governs early microglial proliferation and employs mitochondrial depolarization with caspase 3, 8, and 9 cleavage during oxidant induced apoptosis
    Yan Chen Shang
    Division of Cellular and Molecular Cerebral Ischemia, Wayne State University School of Medicine, Detroit, Michigan 48201, USA
    Curr Neurovasc Res 6:223-38. 2009
    ..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...
  82. ncbi The AMPK-FoxO3A axis as a target for cancer treatment
    Fulvio Chiacchiera
    Laboratory of Signal dependent Transcription Department of Translational Pharmacology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy
    Cell Cycle 9:1091-6. 2010
    ..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 ..
  83. pmc Highly phosphorylated FOXO3A is an adverse prognostic factor in acute myeloid leukemia
    Steven M Kornblau
    Departments of Stem Cell Transplantation and Cellular Therapy and Bioinformatics and Computational Biology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030 4095, USA
    Clin Cancer Res 16:1865-74. 2010
    ..This study evaluated the level of expression and the prognostic relevance of total and phosphorylated FOXO3A protein in AML.
  84. doi IκB kinase overcomes PI3K/Akt and ERK/MAPK to control FOXO3a activity in acute myeloid leukemia
    Nicolas Chapuis
    Institut Cochin, Universite Paris Descartes, CNRS UMR8104, Paris, France
    Blood 116:4240-50. 2010
    ..We therefore investigated the mechanism underlying the regulation of FOXO3a, the only FOXO protein constantly expressed in AML blast cells...
  85. pmc Replication of an association of variation in the FOXO3A gene with human longevity using both case-control and longitudinal data
    Mette Soerensen
    The Danish Aging Research Center, Epidemiology, Institute of Public Health, University of Southern Denmark, Odense C, Denmark
    Aging Cell 9:1010-7. 2010
    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...
  86. pmc Effects of FOXO genotypes on longevity: a biodemographic analysis
    Yi Zeng
    Center for the Study of Aging and Human Development, Medical School of Duke University, Durham, NC 27710, USA
    J Gerontol A Biol Sci Med Sci 65:1285-99. 2010
    ..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 ..
  87. doi Foxo3a suppression of urothelial cancer invasiveness through Twist1, Y-box-binding protein 1, and E-cadherin regulation
    Masaki Shiota
    Department of Urology, Graduate School of Medical Sciences, Kyushu University, Higashi ku, Fukuoka, Japan
    Clin Cancer Res 16:5654-63. 2010
    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...
  88. doi FOXO3a nuclear localisation is associated with good prognosis in luminal-like breast cancer
    Hany Onsy Habashy
    School of Molecular Medical Sciences, University of Nottingham, Nottingham, NG7 2UH, UK
    Breast Cancer Res Treat 129:11-21. 2011
    ..Recent studies have identified Forkhead box O3a (FOXO3a) transcription factor as an intracellular mediator of ERα expression and as an important downstream ..
  89. doi Deacetylation of FOXO3 by SIRT1 or SIRT2 leads to Skp2-mediated FOXO3 ubiquitination and degradation
    F Wang
    Children s Nutrition Research Center, Baylor College of Medicine, Houston, TX 77030, USA
    Oncogene 31:1546-57. 2012
    ..Taken together, our data support the notion that deacetylation of FOXO3 by SIRT1 or SIRT2 facilitates Skp2-mediated FOXO3 poly-ubiquitination and proteasomal degradation...
  90. pmc FOXO3a represses VEGF expression through FOXM1-dependent and -independent mechanisms in breast cancer
    C T Karadedou
    Department of Surgery and Cancer, Cancer Research UK Labs, Imperial College London, Hammersmith Hospital Campus, UK
    Oncogene 31:1845-58. 2012
    ..lines BT474 and SKBR3 as model systems, we tested the possibility that VEGF expression is negatively regulated by FOXO3a. Lapatinib treatment of BT474 or SKBR3 cells resulted in nuclear translocation and activation of FOXO3a, followed ..
  91. doi The tumour suppressor FOXO3 is a key regulator of mantle cell lymphoma proliferation and survival
    Antonia Obrador-Hevia
    Cancer Cell Biology Group, Institut Universitari d Investigacio en Ciencies de la Salut IUNICS, Universitat de les Illes Balears, Palma, Illes Balears, Crta Valldemossa km 7Æ5 E 07122 Palma, Illes Balears, Spain
    Br J Haematol 156:334-45. 2012
    ..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...
  92. doi FOXO3-induced reactive oxygen species are regulated by BCL2L11 (Bim) and SESN3
    Judith Hagenbuchner
    Tyrolean Cancer Research Institute, Innsbruck, Austria
    J Cell Sci 125:1191-203. 2012
    ..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-..
  93. pmc Forkhead transcription factor FOXO3a protein activates nuclear factor κB through B-cell lymphoma/leukemia 10 (BCL10) protein and promotes tumor cell survival in serum deprivation
    Zhaodong Li
    Key Laboratory of Nutrition and Metabolism, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
    J Biol Chem 287:17737-45. 2012
    b>FOXO3a, a member of the Forkhead box O (FoxO) transcription factor family, is believed to be a tumor suppressor because it was found that FOXO3a inactivation promoted cell transformation and tumor progression...
  94. doi FOXO3 as a new IKK-ε-controlled check-point of regulation of IFN-β expression
    Lionel Luron
    Kennedy Institute of Rheumatology, Imperial College of Science, Technology and Medicine, London, United Kingdom
    Eur J Immunol 42:1030-7. 2012
    ..Thus, we identify FOXO3 as a new IKK-ε-controlled check-point of IRF activation and regulation of IFN-β expression, providing new insight into the role of FOXO3 in immune response control...
  95. doi The expression and prognosis of FOXO3a and Skp2 in human ovarian cancer
    Mudan Lu
    Genetic Laboratory, Wuxi Maternal and Child Health Hospital, the Affiliated Hospital of Nanjing Medical University, 48 Huaishu xiang, Wuxi, 214002, Jiangsu, China
    Med Oncol 29:3409-15. 2012
    ..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...
  96. pmc An aqueous extract of Fagonia cretica induces DNA damage, cell cycle arrest and apoptosis in breast cancer cells via FOXO3a and p53 expression
    Matt Lam
    School of Life and Health Sciences, Aston University, Birmingham, United Kingdom
    PLoS ONE 7:e40152. 2012
    ..Plants have proved to be an important source of anti-cancer drugs. Here we have investigated the cytotoxic action of an aqueous extract of Fagonia cretica, used widely as a herbal tea-based treatment for breast cancer...
  97. pmc FOXO3 is a glucocorticoid receptor target and regulates LKB1 and its own expression based on cellular AMP levels via a positive autoregulatory loop
    Nicolas Lützner
    Research Program Infections and Cancer, German Cancer Research Center DKFZ, Heidelberg, Germany
    PLoS ONE 7:e42166. 2012
    ..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...
  98. pmc Genome-wide analysis of FOXO3 mediated transcription regulation through RNA polymerase II profiling
    Astrid Eijkelenboom
    Department of Molecular Cancer Research, University Medical Centre, Utrecht, The Netherlands
    Mol Syst Biol 9:638. 2013
    ..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...
  99. doi FOXO3a is a major target of inactivation by PI3K/AKT signaling in aggressive neuroblastoma
    Evan E Santo
    Department of Oncogenomics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    Cancer Res 73:2189-98. 2013
    ..Here we identify the forkhead transcription factor FOXO3a as a key target of the PI3K/AKT pathway in neuroblastoma...
  100. pmc Activation of protein kinase CK2 attenuates FOXO3a functioning in a PML-dependent manner: implications in human prostate cancer
    A Chatterjee
    Division of Cancer Biology and Inflammatory Disorder, CSIR Indian Institute of Chemical Biology, 4, Raja S C Mullick Road, Kolkata 700032, India
    Cell Death Dis 4:e543. 2013
    ..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...
  101. doi SIRT3 deacetylates FOXO3 to protect mitochondria against oxidative damage
    Anne H H Tseng
    Institute of Biochemistry and Molecular Biology, School of Life Sciences, National Yang Ming University, 11221 Taipei, Taiwan
    Free Radic Biol Med 63:222-34. 2013
    ..Hence, our finding that SIRT3 deacetylates FOXO3 to protect mitochondria against oxidative stress provides a possible direction for aging-delaying therapies and disease intervention. ..

Research Grants67

  1. Saghi Ghaffari; Fiscal Year: 2015
    ..Given the importance of GATA and FoxO factors for regulating diverse processes, the studies will yield broad mechanistic and biological insights. (End of Abstract) ..
  2. Steven A Weinman; Fiscal Year: 2016
    ....
  3. AKT Signaling and Oxidative Stress Regulation of Erythropoiesis
    Saghi Ghaffari; Fiscal Year: 2013
    ..Results from these studies will provide critical information on mechanisms of regulation of erythroid cell division and maturation, and should shed light on fundamental aspects of erythropoiesis. ..
  4. Insulin Signaling and the Heart in Diabetes
    EVAN DALE ABEL; Fiscal Year: 2011
    ..Moreover, elucidation of the signaling mechanisms that regulate autophagy in cardiomyocytes may lead to novel therapies for preventing or modulating heart injury as occurs in diabetes, cardiac ischemia or cardiac hypertrophy. ..
  5. Novel Strategies for Treatment of Myeloproliferative Disorders
    Roya Khosravi-Far; Fiscal Year: 2012
    ..Here we hypothesize that FOXO3a serves as a tumor suppressor in hematopoietic cells and that Bcr-Abl expression removes this suppressive function ..
  6. MARIA JOSE ALMEIDA; Fiscal Year: 2016
    ..Finally, mice overexpressing FoxO3a in osteoblast precursors and their progeny (osteoblasts, osteocytes);and mice in which the three main FoxO ..
  7. The role of the deacetylase Sirt1 in the maintenance of adult neural stem cells
    VICTORIA RAFALSKI; Fiscal Year: 2010
    ..Importantly, the enzymatic activity of Sirt1 can be targeted with small molecule activators or inhibitors, providing a valuable avenue for therapeutic interventions for neurological disorders that may be treated with neural stem cells. ..
  8. Qishen Pang; Fiscal Year: 2014
    ..Our most recent identification of the FANCD2- FOXO3a complex and preliminary characterization of impaired anti-oxidant defense in primary BM cells from FA patients ..
  9. Mitchell Kronenberg; Fiscal Year: 2014
    ..Cbl-b, stimulates Foxp3 induction, via a pathway that leads to increased activity of the transcription factor Foxo3a. Project 2, from Dr...
  10. Jonathan S Weissman; Fiscal Year: 2016
    ..transcription factors extend lifespan and delay age-related disease in animals, and many studies have now linked FOXO3A DNA variants to exceptional longevity in humans...
  11. Role of Fox03a in Regulating the IPF Fibroblast Phenotype
    RICHARD S NHO; Fiscal Year: 2010
    ..have generated data indicating that in IPF fibroblasts, the activated PI3K/Akt signal inhibits the function of the FoxO3a transcriptional activator...
  12. Peter Storz; Fiscal Year: 2014
    ..through the mitochondria and that PKD activated by this pathway regulates survival via the transcription factor FOXO3a. We further hypothesize that the pharmacological inhibition of PKD increases the sensitivity of tumor cells to ROS-..
  13. Role of Cited2 in Hematopoiesis
    Yu Chung Yang; Fiscal Year: 2011
    ....
  14. Wen Xing Ding; Fiscal Year: 2015
    ..Our preliminary studies suggest that the forkhead transcription factor FoxO3a could play a major role in ethanol- induced autophagy...
  15. p66Shc Signaling Functions in Cardiomyocytes
    Susan F Steinberg; Fiscal Year: 2013
    ..a target of an adrenergic receptor pathway involving ROS and PKC that is localized to caveolae and regulates AKT-FOXO3a phosphorylation and anti-oxidant gene expression...
  16. Peixin Yang; Fiscal Year: 2016
    ..Our published data in caspase 8 and JNK2, preliminary data in amelioration of diabetic embryopathy by Foxo3a deficiency and preventive effect of phytochemical EGCG on hyperglycemia-induced malformations via inhibition of ..
  17. Arunabh Bhattacharya; Fiscal Year: 2014
    ..abstract_text> ..
  18. Estrogen: Neuroprotection in the Perimenopause
    Anne M Etgen; Fiscal Year: 2010
    ..later times after ischemia;3) inactivation of Akt and subsequent activation of the forkhead transcription factor FKHRL1 at early times after ischemia...
  19. The role of SIRT1/FOXO4 pathway in podocyte apoptosis of diabetes mellitus
    PETER YENLUNG CHUANG; Fiscal Year: 2013
    ..This study could give new insight into the pathogenesis of diabetic nephropathy and provide targets for novel therapy. ..
  20. Robert C Bast; Fiscal Year: 2016
    ..associates directly with nucleating autophagic vesicles through lipid-lipid interactions, inducing Atg4 through FoxO3a to cleave MAP-LC3, facilitating vesicle membrane elongation...
  21. Wafik S El-Deiry; Fiscal Year: 2016
    ..level, TIC10 causes potent antitumor effects and TRAIL-induction that is mediated by the transcription factor Foxo3a, which directly regulates the TRAIL gene promoter...
  22. Modeling Parkinson's Disease by Deleting FoxO Factors from Dopaminergic Neurons
    BRENDAN DAVID LOOYENGA; Fiscal Year: 2012
    ..Loss of FoxO factor expression is expected to cause progressive neuronal cell death in mice due to the accumulation of cellular damage from unrestrained oxidative stress and decreased mitochondrial energy production. ..
  23. Functions and Interactions dFOXO in Drosopila Aging
    Marc Tatar; Fiscal Year: 2010
    The D. melanogaster transcription factor dFOXO is homologous to C. elegans daf-16 and to human FOXO3a. Regulated through insulin/IGF signaling, DAF-16 helps control dauer and aging...
  24. SHOSHANA BARTELL; Fiscal Year: 2014
    ..This work should advance knowledge of how oxidative stress via FoxO activation alters bone mass, and provide a better understanding of the mechanisms controlling sex steroid deficiency- or age-related osteoporosis. ..
  25. p66/Insulin Like Growth Factor-1 Reno-Protection in Diabetes
    LEONARD GERALD MEGGS; Fiscal Year: 2010
    ..recombination with p66ShcA-/- mouse, results in the translocation of the potent stress response regulator FOXO3a to the nucleus, where it orchestrates the stress response program...
  26. Andrey Sorokin; Fiscal Year: 2016
    ..We will test the hypothesis that p66 Shc promotes GMC proliferation via inactivation of transcription factor FOXO3a and restricts GMC contractility through regulation of calcium influx...
  27. Natarajan Muthusamy; Fiscal Year: 2016
    ..SHP1 activation leads to decreased PI3-Kinase activity and AKT phosphorylation concomitant with FOXO3A accumulation in the nucleus and induction of the pro-apoptotic gene BIM and CLL cell death...
  28. Derivation of Mature Oocytes from Human Primordial Follicles
    AARON JW HSUEH; Fiscal Year: 2010
    ..Frozen ovaries from cancer patients before chemo- or radiation therapy could also be used to generate mature oocytes for infertility treatment. ..
  29. ANTHONY JOHN DONATO; Fiscal Year: 2015
    ..oxidative, -inflammatory and -apoptotic signaling molecules;nuclear factor kappa B (NFkB), p53, and forkhead foxO (FoxO3a) via an increase a nuclear deacetylase SIRT-1 in MA/O mice and (3) to determine if activation of the nuclear ..
  30. Stephen M Hedrick; Fiscal Year: 2016
    ..The results will have direct implications for the progression of long co-evolved viral diseases such as HIV, Herpes, and Hepatitis C virus. ..
  31. John L Fowlkes; Fiscal Year: 2015
    ..Together, these studies will provide critical mechanistic and pre-clinical information needed to better understand how corrections in insulin and/or IGF-I in diabetes may be beneficial in preventing and treating diabetic osteopathy. ..
  32. Spatio-temporal control of FOXO3
    Robert G Kalb; Fiscal Year: 2013
    ..The deliverable of this proposal is a versatile mouse that permits spatio-temporal control of FOXO3 gene transcription. ..
  33. Genetic Regulation of the Response to Dietary Restriction
    ANDREW G DILLIN; Fiscal Year: 2012
    ..SMK-1 was originally characterized as a co-regulator of the FOXO3a orthologue, DAF- 16, required to mediate insulin/IGF-1 signaling (IIS)...
  34. PHILIP ROPER; Fiscal Year: 2015
    ..We have already been able to show that FoxO3a, vital in upregulating genes to combat rising oxidative stress, is elevated in the fracture callus of mice two ..
  35. FOXO: A Target for Prostate Cancer Prevention
    Sanjeev Shukla; Fiscal Year: 2010
    ..Furthermore, levels of FOXO3A were significantly higher in the cytosolic fraction than the nucleus as a function of age and disease progression...
  36. Thomas A Rando; Fiscal Year: 2016
    ..Within that context, we seek to identify mechanisms to restore aged SCs to their youthful state by modulating the reversible, epigenetic determinants of aged SC function. ..
  37. Wei Zhou; Fiscal Year: 2015
    ..Mechanistically, we found that EGFR/AKT activation led to increased phosphorylation of FoxO3A at threonine 32 (Thr32) in LKB1 wild-type cells, but not in LKB1-null cells...
  38. Molecular Mechanisms that Cause Muscle Atrophy
    Alfred L Goldberg; Fiscal Year: 2012
    ..g. cancer, sepsis, renal failure) and aging. ..
  39. David A Hildeman; Fiscal Year: 2016
    ..our data suggest a model in which chronic cytokine signaling increases in vivo survival of Treg by enhancing FOXO3a-dependent suppression of Bim-expression...
  40. Sanjay Gupta; Fiscal Year: 2014
    ..and its modulation by apigenin, iii) the role of IKK[unreadable] on activity and cellular distribution of forkhead box O3a and its modulation by apigenin, and iv) IKKa/[unreadable] as a molecular target for the anticancer effects of ..
  41. Robert G Kalb; Fiscal Year: 2015
    ..The FOXO3a transcription factor plays a key role in this process in worms and flies, but its function in vertebrates is ..
  42. MELANIE MARIA OTT; Fiscal Year: 2014
    ..Tat by inhibiting SIRT1 induces hyperacetylation of several SIRT1 targets including proapoptotic factors p53 and Foxo3A. Since both factors are important regulators of T-cell death during HIV infection, we will study how Tat ..
  43. Nox4 and Cardiac Fibrosis
    Dan Sorescu; Fiscal Year: 2012
    ..and nuclear translocation of transcription factors Smad2/3;3) the novel redox-sensitive transcription factor FoxO3A is required for TGF-1 and Ang II expression of pro-fibrotic proteins and finally 4) Nox4 regulates de-acetylation ..
  44. Role of serum- and glucocorticoid-regulated kinase-1 in electrical remodeling
    Anthony Rosenzweig; Fiscal Year: 2013
    ..Thus understanding SGK1's role in the heart could have important practical implications, and the current application would help advance our understanding of the potential of SGK1 as a therapeutic target. ..
  45. Targeting the ROS-p38 MAPK Pathway as a Novel Strategy for Stem Cell Expansion
    GAVIN YONG WANG; Fiscal Year: 2012
    ..Such information will be essential to the development of innovative culture strategies for the ex vivo expansion of HSCs. ..
  46. Protein S: Neurovascular Protection in Stroke
    Berislav V Zlokovic; Fiscal Year: 2010
    ..G. Lemke (Salk) (Tyro 3 RTK mutants), Dr. R. Freeman (Rochester) (various Akt, Bel and FKHRL1 mutants), Dr. M. Moskowitz (Harvard) (intrinsic/extrinsic apoptotic signaling), Dr. B...
  47. CHENDIL DAMODARAN; Fiscal Year: 2015
    ..Our preliminary data demonstrate that, concomitant to Akt inhibition in ADPC and AIPC cells, WA activates FOXO3a, which in turn activates prostate apoptosis response-4 (Par-4), a protein that selectively induces apoptosis in ..
  48. Neuroprotective microRNA pathways
    Scott E Counts; Fiscal Year: 2013
    ..neuroprotective cell stress responses, the deacetylase sirtuin 1 (sirt1) and the forkhead transcription factor foxo3a;pilot qPCR studies using the same frontal cortex samples revealed that both sirt1 and foxo3a mRNA levels were ..
  49. Laren Becker; Fiscal Year: 2014
    ..abstract_text> ..
  50. EPIGENETIC AGING OF THE OXIDATIVE STRESS RESPONSE IN THE MOUSE RPE
    Zeljka Smit McBride; Fiscal Year: 2010
    ..The set includes Er1, Err1, Foxo3a, Nrf2, Pgc11, Prdx3, p66/Shc1, Sirt1, Sod2, Txn2, Txnrd2, and 14-3-38...
  51. SUZANA SAVKOVIC; Fiscal Year: 2015
    ..Although mechanisms of colon cancer progression are complex, the inhibition of LDs may provide an effective blockade to tumor progression in patients with obesity promoted colonic tumor progression. ..
  52. Bruce J Shenker; Fiscal Year: 2015
    ..2) to determine if CdtB-induced apoptosis results from activation of the intrinsic apoptotic pathway mediated by FOXO3a activation, and (3) to determine the role of cholesterol in CdtB mediated PIP3 depletion leading to cell cycle ..
  53. p66ShcA in HIV associated Nephropathy
    Pravin C Singhal; Fiscal Year: 2013
    ..Based on these results we hypothesize that in HIV-1 infection, inhibition of p66ShcA activates a Foxo3A- dependent stress program that promotes the survival phenotype...
  54. Donald Craig Willcox; Fiscal Year: 2014
    ....
  55. Control of Lymphocyte Homeostasis by Foxo Transcription Factors
    Stephen M Hedrick; Fiscal Year: 2010
    ..abstract_text> ..
  56. BRADLEY JOHN WILLCOX; Fiscal Year: 2014
    ..Our work will focus on identifying the mechanism(s) of action of FOXO3A on healthy aging and longevity...
  57. Effect of Rhamnetin on Oxidative Stress and Prostate Cancer
    Sanjeev Shukla; Fiscal Year: 2013
    ..at cellular and organismal level, which correlates with reduced serum levels of secreted KL protein and loss of FOXO3a from the nucleus...
  58. XIAONAN H WANG; Fiscal Year: 2016
    ..Specifically, we found that 1) PTEN and FoxO3A, two proteins that are involved with protein degradation, were up-regulated in muscle from CKD animals;2) YY1, a ..
  59. BRADLEY JOHN WILLCOX; Fiscal Year: 2014
    ..2) Identified environmental predictors of healthy aging and longevity in a longitudinal study, 3) Found a gene (FOXO3A) with variants strongly associated with healthy aging and longevity;4) Replicated the CETP gene association with ..
  60. Alan A Aderem; Fiscal Year: 2016
    ..Systems approaches will then be used to integrate Foxo3 and the miRNAs into a global IRF7 regulatory network. Finally, we will examine the in vivo relevance of the IRF7- FOXO3-miRNA regulatory circuit in a mouse model of VSV infection. ..
  61. Asgerally T Fazleabas; Fiscal Year: 2016
    ..Specific Aim 2 will test the hypothesis that the Notch1 mediated decrease in FOXO3a and Notch1 mediated increase in IL-11 is a necessary prerequisite for the initiation of decidualization...
  62. Peter M Gordon; Fiscal Year: 2015
    ..in the response of c-KIT dependent cancers to imatinib therapy, and 3) To investigate the role of BIM and FOXO3a in connecting apoptosis and autophagy in the response of c-KIT dependent cancers to targeted therapy...
  63. STEPHANIE KAYE WATKINS; Fiscal Year: 2014
    ..Specifically, the data generated during the R00 phase of the award will provide the groundwork for the candidate to apply for an R01 by the end of her second year as an independent investigator. ..
  64. C-MYC EXPRESSION AND APOPTOSIS IN B CELLS
    GAIL SONENSHEIN; Fiscal Year: 2007
    ..ef the p27 gene; 3) c-Myc can bind to the Inr element of the p27 gene in the presence of Max; 4) Forkhead FKHRL1 factor is induced following anti-IgM treatment; 5) transactivation of p27 promoter by FKHRL1 can be repressed by c-..
  65. Regulation of Ovarian Follicle Activation
    DIEGO CASTRILLON; Fiscal Year: 2009
    ..of how this pathway regulates primordial follicle activation;4) screen for genetic variants or mutations of the FOXO3A gene--the only known potent suppressor of primordial follicle activation-in women with premature ovarian failure (..
  66. A novel anti-hypertrophic pathway in the heart
    Peifeng Li; Fiscal Year: 2010
    ..b>FOXO3a is a transcriptional factor. Most recent studies show that it can negatively regulate cardiac hypertrophy...
  67. Characterization of FOXO3A 419T Variant in Fragile X Premutation-Related POF
    Stephen Collins; Fiscal Year: 2009
    ..One possible mechanism to explain premutation-related POP is altered translational regulation of FOXO3A by FMRP...