Foxo4

Summary

Gene Symbol: Foxo4
Description: forkhead box O4
Alias: Afxh, Mllt7, afx, forkhead box protein O4, fork head domain transcription factor AFX1, forkhead protein, myeloid/lymphoid or mixed lineage-leukemia translocation to 7 homolog
Species: mouse

Top Publications

  1. pmc Hepatic suppression of Foxo1 and Foxo3 causes hypoglycemia and hyperlipidemia in mice
    Kebin Zhang
    Division of Molecular Cardiology, Cardiovascular Research Institute, College of Medicine, Texas A and M Health Science Center, Central Texas Veterans Health Care System, Temple, Texas 76504, USA
    Endocrinology 153:631-46. 2012
  2. pmc Hepatic FoxOs regulate lipid metabolism via modulation of expression of the nicotinamide phosphoribosyltransferase gene
    Rongya Tao
    Department of Biochemistry and Molecular Biology, Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, Indiana 46202 USA
    J Biol Chem 286:14681-90. 2011
  3. pmc FoxOs function synergistically to promote glucose production
    Rebecca A Haeusler
    Department of Medicine, Columbia University, New York, New York 10032, USA
    J Biol Chem 285:35245-8. 2010
  4. pmc Impaired generation of 12-hydroxylated bile acids links hepatic insulin signaling with dyslipidemia
    Rebecca A Haeusler
    Department of Medicine, Columbia University, New York, NY 10032, USA
    Cell Metab 15:65-74. 2012
  5. pmc FoxOs integrate pleiotropic actions of insulin in vascular endothelium to protect mice from atherosclerosis
    Kyoichiro Tsuchiya
    Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA
    Cell Metab 15:372-81. 2012
  6. pmc FoxO-mediated defense against oxidative stress in osteoblasts is indispensable for skeletal homeostasis in mice
    Elena Ambrogini
    Division of Endocrinology and Metabolism, Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences and the Central Arkansas Veterans Healthcare System, Little Rock, AR 72205, USA
    Cell Metab 11:136-46. 2010
  7. pmc FoxOs cooperatively regulate diverse pathways governing neural stem cell homeostasis
    Ji Hye Paik
    Department of Medical Oncology, Belfer Institute for Applied Cancer Science, Harvard Medical School, Boston, MA 02115, USA
    Cell Stem Cell 5:540-53. 2009
  8. pmc The autophagy-related gene 14 (Atg14) is regulated by forkhead box O transcription factors and circadian rhythms and plays a critical role in hepatic autophagy and lipid metabolism
    Xiwen Xiong
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
    J Biol Chem 287:39107-14. 2012
  9. pmc Expanded granulocyte/monocyte compartment in myeloid-specific triple FoxO knockout increases oxidative stress and accelerates atherosclerosis in mice
    Kyoichiro Tsuchiya
    Naomi Berrie Diabetes Center, 1150 St Nicholas Ave, Russ Berrie Pavilion Room 238, NY 10032, USA
    Circ Res 112:992-1003. 2013
  10. pmc Advanced glycation endproducts induce podocyte apoptosis by activation of the FOXO4 transcription factor
    P Y Chuang
    Division of Nephrology, Department of Medicine, Mount Sinai School of Medicine, James J Peters VA Medical Center, New York, New York 10029, USA
    Kidney Int 72:965-76. 2007

Research Grants

  1. Convergence of Nuclear Receptor and Forkhead Signaling
    Paul Dowell; Fiscal Year: 2004
  2. LH ACTION IN OVARIAN CELL DIFFERENTIATION
    Joanne Richards; Fiscal Year: 2007
  3. Ovarian Follicular Developmental and Hormone Action
    Joanne Richards; Fiscal Year: 2007
  4. LH ACTION IN OVARIAN CELL DIFFERENTIATION
    Joanne Richards; Fiscal Year: 2008
  5. Role of FOXO4 in atherosclerosis
    Zhi Ping Liu; Fiscal Year: 2010

Scientific Experts

  • Joanne Richards
  • Tatsuo Furuyama
  • Karen C Arden
  • Zhi Ping Liu
  • Marco F M Hoekman
  • Jun Nakae
  • Vincent E Sollars
  • PAUL T DOWELL
  • Peter Y Chuang
  • Arjan B Brenkman
  • Jennifer S Moylan
  • Ronald A Depinho
  • Domenico Accili
  • Rongya Tao
  • Xiwen Xiong
  • Kyoichiro Tsuchiya
  • Rebecca A Haeusler
  • Ji Hye Paik
  • X Charlie Dong
  • Ja Young Kim-Muller
  • Diego H Castrillon
  • Min Zhu
  • Boyi Gan
  • Xiaozhong Shi
  • Wenwei Zhang
  • Elena Ambrogini
  • Stephen M Sykes
  • Zuzana Tothova
  • D Gary Gilliland
  • Zhihu Ding
  • Shan Jiang
  • Hao Li
  • Taiyi Kuo
  • Giulia Milan
  • Nilay Kuscu
  • Chi Wai So
  • Shoshana M Bartell
  • Insug O-Sullivan
  • Terry G Unterman
  • A Lin
  • Dara Slopack
  • Anthony W Ferrante
  • Roger Gutierrez-Juarez
  • Brian R Rosborough
  • Chu Xia Deng
  • Yusuke S Hori
  • Christian Günschmann
  • Hongxia Ren
  • Alan R Tall
  • Li Han
  • Sayan Nandi
  • Sarah A Reed
  • CHARLES A O'BRIEN
  • Xiong Deng
  • Robert L Jilka
  • Maria Almeida
  • Kebin Zhang
  • Carrie L Welch
  • Kristan E van der Vos
  • Stavros C Manolagas
  • Robert S Weinstein
  • Lan Xiang
  • Meredith J Goertz
  • Ratakorn Srisuttee
  • Hunki Paek
  • Yasunari Yamanaka
  • Daniel J Garry
  • David T Scadden
  • Melanie G Cornejo
  • Qing Jun Zhang
  • Hongwu Zheng
  • Wen Zhou
  • Hong Lei
  • Biao Wang
  • Gerald Chu
  • Anne Catherine Feutz
  • Lynda Chin
  • Wing H Wong
  • Heather J Evans-Anderson
  • Patricia S Pardo
  • Caroline Bouchard
  • Noboru Motoyama
  • Patrick J E C Wijchers
  • Wei Liu
  • Lorena Martínez-Gac
  • Taisuke Hosaka
  • Salmaan A Khan
  • Douglas G Mashek
  • Olga Ilkayeva
  • So Young Bu

Detail Information

Publications74

  1. pmc Hepatic suppression of Foxo1 and Foxo3 causes hypoglycemia and hyperlipidemia in mice
    Kebin Zhang
    Division of Molecular Cardiology, Cardiovascular Research Institute, College of Medicine, Texas A and M Health Science Center, Central Texas Veterans Health Care System, Temple, Texas 76504, USA
    Endocrinology 153:631-46. 2012
    ..Cell-based studies established that the Foxo forkhead transcription factors Forkhead box O (Foxo)-1, Foxo3, and Foxo4 are inactivated by insulin via a phosphatidylinositol 3-kinase/Akt-dependent pathway, but the role of Foxo ..
  2. pmc Hepatic FoxOs regulate lipid metabolism via modulation of expression of the nicotinamide phosphoribosyltransferase gene
    Rongya Tao
    Department of Biochemistry and Molecular Biology, Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, Indiana 46202 USA
    J Biol Chem 286:14681-90. 2011
    ..the phenotypic consequences of liver-specific deletion of three members of the FoxO family: FoxO1, FoxO3, and FoxO4. These liver-specific triply null mice, designated LTKO, exhibited elevated triglycerides in the liver on regular ..
  3. pmc FoxOs function synergistically to promote glucose production
    Rebecca A Haeusler
    Department of Medicine, Columbia University, New York, New York 10032, USA
    J Biol Chem 285:35245-8. 2010
    ..transcription factors to HGP, we created double and triple liver-specific knock-outs lacking FoxO1, FoxO3, and FoxO4 or the related protein FoxA2...
  4. pmc Impaired generation of 12-hydroxylated bile acids links hepatic insulin signaling with dyslipidemia
    Rebecca A Haeusler
    Department of Medicine, Columbia University, New York, NY 10032, USA
    Cell Metab 15:65-74. 2012
    ..We propose that generation of 12α-hydroxylated products of BA metabolism represents a signaling mechanism linking hepatic lipid abnormalities with type 2 diabetes, and a treatment target for this condition...
  5. pmc FoxOs integrate pleiotropic actions of insulin in vascular endothelium to protect mice from atherosclerosis
    Kyoichiro Tsuchiya
    Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA
    Cell Metab 15:372-81. 2012
    ..The data demonstrate that FoxO inhibition in endothelial cells has the potential to mediate wide-ranging therapeutic benefits for diabetes-associated cardiovascular disease...
  6. pmc FoxO-mediated defense against oxidative stress in osteoblasts is indispensable for skeletal homeostasis in mice
    Elena Ambrogini
    Division of Endocrinology and Metabolism, Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences and the Central Arkansas Veterans Healthcare System, Little Rock, AR 72205, USA
    Cell Metab 11:136-46. 2010
    ..Conditional deletion of FoxO1, FoxO3, and FoxO4 in 3-month-old mice resulted in an increase in oxidative stress in bone and osteoblast apoptosis and a decrease in ..
  7. pmc FoxOs cooperatively regulate diverse pathways governing neural stem cell homeostasis
    Ji Hye Paik
    Department of Medical Oncology, Belfer Institute for Applied Cancer Science, Harvard Medical School, Boston, MA 02115, USA
    Cell Stem Cell 5:540-53. 2009
    ..Thus, the FoxO family coordinately regulates diverse genes and pathways to govern key aspects of NSC homeostasis in the mammalian brain...
  8. pmc The autophagy-related gene 14 (Atg14) is regulated by forkhead box O transcription factors and circadian rhythms and plays a critical role in hepatic autophagy and lipid metabolism
    Xiwen Xiong
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
    J Biol Chem 287:39107-14. 2012
    ..In summary, our data suggest that Atg14 is a new target gene of FoxOs and the core clock machinery, and this gene plays an important role in hepatic lipid metabolism...
  9. pmc Expanded granulocyte/monocyte compartment in myeloid-specific triple FoxO knockout increases oxidative stress and accelerates atherosclerosis in mice
    Kyoichiro Tsuchiya
    Naomi Berrie Diabetes Center, 1150 St Nicholas Ave, Russ Berrie Pavilion Room 238, NY 10032, USA
    Circ Res 112:992-1003. 2013
    ..Increased neutrophil and monocyte counts are often associated with an increased risk of atherosclerosis, but their relationship to insulin sensitivity is unknown...
  10. pmc Advanced glycation endproducts induce podocyte apoptosis by activation of the FOXO4 transcription factor
    P Y Chuang
    Division of Nephrology, Department of Medicine, Mount Sinai School of Medicine, James J Peters VA Medical Center, New York, New York 10029, USA
    Kidney Int 72:965-76. 2007
    ..Exposure to AGE-BSA was associated with Akt dephosphorylation and FOXO4 transcriptional activation leading to an increase in the expression of an effector protein of apoptosis, Bim...
  11. pmc FoxOs are lineage-restricted redundant tumor suppressors and regulate endothelial cell homeostasis
    Ji Hye Paik
    Department of Medical Oncology, Dana Farber Cancer Institute, Brigham and Women s Hospital, and Harvard Medical School, Boston, MA 02115, USA
    Cell 128:309-23. 2007
    ..The highly related members of the mammalian FoxO transcription factor family, FoxO1, FoxO3, and FoxO4, represent one of several effector arms of PI3K-AKT signaling, prompting genetic analysis of the role of FoxOs in ..
  12. pmc Liver sinusoidal endothelial cells link hyperinsulinemia to hepatic insulin resistance
    Kyoichiro Tsuchiya
    Naomi Berrie Diabetes Center and Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York, USA
    Diabetes 62:1478-89. 2013
    ..The findings are consistent with a model in which excessive, rather than reduced, insulin signaling in ECs predisposes to systemic insulin resistance, prompting a reevaluation of current approaches to insulin sensitization...
  13. pmc Blunted refeeding response and increased locomotor activity in mice lacking FoxO1 in synapsin-Cre-expressing neurons
    Hongxia Ren
    Berrie Diabetes Center, New York, New York
    Diabetes 62:3373-83. 2013
    ....
  14. pmc The FoxO-BNIP3 axis exerts a unique regulation of mTORC1 and cell survival under energy stress
    A Lin
    Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
    Oncogene 33:3183-94. 2014
    ..Together, our study uncovers a novel signaling circuit functioning to mediate cellular energy responses to control cell growth and survival. These findings also have important implications to human cancers. ..
  15. pmc Hepatic SREBP-2 and cholesterol biosynthesis are regulated by FoxO3 and Sirt6
    Rongya Tao
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN
    J Lipid Res 54:2745-53. 2013
    ..Remarkably, Sirt6 or FoxO3 overexpression improves hypercholesterolemia in diet-induced or genetically obese mice. In summary, our data suggest an important role of hepatic Sirt6 and FoxO3 in the regulation of cholesterol homeostasis. ..
  16. pmc FoxO3 transcription factor and Sirt6 deacetylase regulate low density lipoprotein (LDL)-cholesterol homeostasis via control of the proprotein convertase subtilisin/kexin type 9 (Pcsk9) gene expression
    Rongya Tao
    From the Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202
    J Biol Chem 288:29252-9. 2013
    ..Also remarkably, overexpression of Sirt6 in high fat diet-fed mice lowers LDL-cholesterol. Overall, our data suggest that FoxO3 and Sirt6, two longevity genes, can reduce LDL-cholesterol levels through regulation of the Pcsk9 gene. ..
  17. pmc Integrated Regulation of Hepatic Lipid and Glucose Metabolism by Adipose Triacylglycerol Lipase and FoxO Proteins
    Wenwei Zhang
    Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA Medical Research Service, Jesse Brown VA Medical Center, Chicago, IL 60612, USA
    Cell Rep 15:349-59. 2016
    ..These results indicate that intrahepatic lipolysis plays a critical role in mediating and integrating the regulation of glucose and lipid metabolism downstream of FoxO proteins. ..
  18. pmc Altered Plasma Profile of Antioxidant Proteins as an Early Correlate of Pancreatic β Cell Dysfunction
    Taiyi Kuo
    From the Department of Medicine and Berrie Diabetes Center, Columbia University College of Physicians and Surgeons, New York, New York 10032 and
    J Biol Chem 291:9648-56. 2016
    ..These results suggest that a reduced complement of antioxidants in response to a mixed secretagogue challenge is an early correlate of future β cell failure. ..
  19. pmc FoxO4 promotes early inflammatory response upon myocardial infarction via endothelial Arg1
    Min Zhu
    From the Departments of Internal Medicine and Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX M Z, S C G, Z W, R L, J A H, J S, Z P L and Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, PA S M M
    Circ Res 117:967-77. 2015
    ..Unfortunately, it is also a key component of subsequent heart failure pathology. Transcription factor forkhead box O4 (FoxO4) regulates a variety of biological processes, including inflammation. However, its role in MI remains unknown.
  20. doi FOXO1, FOXO3, AND FOXO4 are differently expressed during mouse oocyte maturation and preimplantation embryo development
    Nilay Kuscu
    Department of Histology and Embryology, School of Medicine, Akdeniz University, Campus, 07070 Antalya, Turkey
    Gene Expr Patterns 18:16-20. 2015
    ..Presence and localizations of FoxO1, FoxO3 and FoxO4 proteins have been determined with immunofluorescence staining...
  21. pmc Regulation of autophagy and the ubiquitin-proteasome system by the FoxO transcriptional network during muscle atrophy
    Giulia Milan
    Venetian Institute of Molecular Medicine, Via Orus 2, 35129 Padova, Italy
    Nat Commun 6:6670. 2015
    ..Our findings underscore the central function of FoxOs in coordinating a variety of stress-response genes during catabolic conditions. ..
  22. ncbi Convergence of peroxisome proliferator-activated receptor gamma and Foxo1 signaling pathways
    Paul Dowell
    Biological Chemistry and Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    J Biol Chem 278:45485-91. 2003
    ..A more general convergence of nuclear hormone receptor and forkhead factor pathways may be important for multiple biological processes and this convergence may be evolutionarily conserved...
  23. pmc Integrated control of hepatic lipogenesis versus glucose production requires FoxO transcription factors
    Rebecca A Haeusler
    1 Department of Pathology and Cell Biology, Columbia University, New York, New York 10032, USA 2 Department of Medicine, Columbia University, New York, New York 10032, USA
    Nat Commun 5:5190. 2014
    ....
  24. pmc Metabolic inflexibility impairs insulin secretion and results in MODY-like diabetes in triple FoxO-deficient mice
    Ja Young Kim-Muller
    Naomi Berrie Diabetes Center, Department of Medicine, Columbia University, New York, NY 10032, USA
    Cell Metab 20:593-602. 2014
    ..We propose that defects in both pancreatic β cell function and mass arise through FoxO-dependent mechanisms during diabetes progression. ..
  25. pmc Forkhead BoxO transcription factors restrain exercise-induced angiogenesis
    Dara Slopack
    Angiogenesis Research Group, Faculty of Health, York University, Toronto, Canada
    J Physiol 592:4069-82. 2014
    ..In conclusion, FoxO proteins can delay exercise-induced angiogenesis, and thus are critical regulators of the physiological angiogenic response in skeletal muscle...
  26. pmc FoxO proteins restrain osteoclastogenesis and bone resorption by attenuating H2O2 accumulation
    Shoshana M Bartell
    1 Division of Endocrinology and Metabolism, Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences and the Central Arkansas Veterans Healthcare System, Little Rock, Arkansas 72205, USA 2
    Nat Commun 5:3773. 2014
    ....
  27. pmc Regulation of FOXOs and p53 by SIRT1 modulators under oxidative stress
    Yusuke S Hori
    Department of Pharmacology, School of Medicine, Sapporo Medical University, Sapporo, Japan
    PLoS ONE 8:e73875. 2013
    ..In p53-independent cell protective pathway, we found that FOXO1, FOXO3a, and FOXO4 were involved in SOD2's upregulation by resveratrol...
  28. pmc Deletion of hepatic FoxO1/3/4 genes in mice significantly impacts on glucose metabolism through downregulation of gluconeogenesis and upregulation of glycolysis
    Xiwen Xiong
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America
    PLoS ONE 8:e74340. 2013
    ..Collectively, FoxO1/3/4 transcription factors play important roles in hepatic glucose homeostasis. ..
  29. pmc FoxO4 inhibits atherosclerosis through its function in bone marrow derived cells
    Min Zhu
    Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
    Atherosclerosis 219:492-8. 2011
    ..Our objectives were to determine whether and how inactivation of Foxo4, a member of the FoxO family, in vivo promotes atherosclerosis.
  30. pmc Alteration of forkhead box O (foxo4) acetylation mediates apoptosis of podocytes in diabetes mellitus
    Peter Y Chuang
    Division of Nephrology, Department of Medicine, Mount Sinai School of Medicine, New York, New York, United States of America
    PLoS ONE 6:e23566. 2011
    ..accumulate in patients with diabetes and promote the apoptosis of podocyte by activating the forkhead box O4 (Foxo4) transcription factor to increase the expression of a pro-apoptosis gene, Bcl2l11...
  31. pmc Crosstalk between NOTCH and AKT signaling during murine megakaryocyte lineage specification
    Melanie G Cornejo
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    Blood 118:1264-73. 2011
    ....
  32. pmc Inhibition of FoxO transcriptional activity prevents muscle fiber atrophy during cachexia and induces hypertrophy
    Sarah A Reed
    Department of Physical Therapy, 101 S Newell Dr, University of Florida, Gainesville, FL 32611, USA
    FASEB J 26:987-1000. 2012
    ....
  33. pmc Insulin/IGF-1 controls epidermal morphogenesis via regulation of FoxO-mediated p63 inhibition
    Christian Günschmann
    Department of Dermatology, University of Cologne, 50931 Cologne, Germany
    Dev Cell 26:176-87. 2013
    ..Collectively, the present study reveals a critical role for IIS-dependent control of p63 activity in coordination of ACD and stratification during epithelial morphogenesis. ..
  34. pmc Tetrahydrocurcumin extends life span and inhibits the oxidative stress response by regulating the FOXO forkhead transcription factor
    Lan Xiang
    Department of Cognitive Brain Sciences, National Center for Geriatrics and Gerontology, Obu, Aichi, 474 8511, Japan
    Aging (Albany NY) 3:1098-109. 2011
    ..In NIH3T3 cells, THC induced nuclear accumulation of FOXO4, a member of the FOXO family of transcription factors, by inhibiting phosphorylation of protein kinase B (PKB)/Akt...
  35. pmc FoxO1 inhibits sterol regulatory element-binding protein-1c (SREBP-1c) gene expression via transcription factors Sp1 and SREBP-1c
    Xiong Deng
    Department of Medicine, Memphis Veterans Affairs Medical Center, Memphis, Tennessee 38104, USA
    J Biol Chem 287:20132-43. 2012
    ....
  36. pmc Murine dendritic cell rapamycin-resistant and rictor-independent mTOR controls IL-10, B7-H1, and regulatory T-cell induction
    Brian R Rosborough
    Thomas E Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
    Blood 121:3619-30. 2013
    ..These findings identify the first known RAPA-insensitive mTOR pathway that is not mediated solely by mTORC2 and have implications for the use of catalytic mTOR inhibitors in inflammatory disease settings...
  37. pmc The CSF-1 receptor ligands IL-34 and CSF-1 exhibit distinct developmental brain expression patterns and regulate neural progenitor cell maintenance and maturation
    Sayan Nandi
    Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, New York, NY 10461, USA
    Dev Biol 367:100-13. 2012
    ..Thus our results also indicate novel roles for the CSF-1R in the regulation of corticogenesis...
  38. doi Modulation of glutamine metabolism by the PI(3)K-PKB-FOXO network regulates autophagy
    Kristan E van der Vos
    Department of Immunology, University Medical Center Utrecht, Utrecht 3584CX, The Netherlands
    Nat Cell Biol 14:829-37. 2012
    ..global transcriptional analyses after conditional activation of the key components PI(3)K, PKB/Akt, FOXO3 and FOXO4. Using this pathway approach, we identified glutamine synthetase as being transcriptionally regulated by PI(3)K-..
  39. pmc Foxk1 promotes cell proliferation and represses myogenic differentiation by regulating Foxo4 and Mef2
    Xiaozhong Shi
    Lillehei Heart Institute, University of Minnesota Twin Cities, Minneapolis, MN 55455, USA
    J Cell Sci 125:5329-37. 2012
    ..Utilizing an array of technologies, we establish that Foxk1 represses the transcriptional activity of Foxo4 and Mef2 and physically interacts with Foxo4 and Mef2, thus promoting MPC proliferation and antagonizing the ..
  40. pmc Control of cyclin G2 mRNA expression by forkhead transcription factors: novel mechanism for cell cycle control by phosphoinositide 3-kinase and forkhead
    Lorena Martínez-Gac
    Department of Immunology and Oncology, Centro Nacional de Biotecnologia CSIC, Universidad Autonoma de Madrid, Cantoblanco, Madrid E 28049, Spain
    Mol Cell Biol 24:2181-9. 2004
    ..These results show that FoxO genes regulate cyclin G2 expression, illustrating a new role for phosphoinositide 3-kinase and FoxO transcription factors in the control of cell cycle entry...
  41. doi Up-regulation of Foxo4 mediated by hepatitis B virus X protein confers resistance to oxidative stress-induced cell death
    Ratakorn Srisuttee
    WCU Department of Cogno Mechatronics Engineering, BK21 Nanofusion Technology Team, Pusan National University, Busan, Republic of Korea
    Int J Mol Med 28:255-60. 2011
    ..Here, we show that HBX induces the up-regulation of Forkhead box class O 4 (Foxo4) not only in Chang cells stably expressing HBX (Chang-HBX) but also in primary hepatic tissues from HBX-transgenic ..
  42. ncbi The FoxO transcription factors and metabolic regulation
    Jun Nakae
    21st Century COE Program for Signal Transduction Disease, Kobe University Graduate School of Medicine, Kobe 650 0017, Japan
    FEBS Lett 582:54-67. 2008
    ..The understanding of molecular mechanism how FoxOs affect glucose or lipid metabolism will shed light on the novel therapy of type 2 diabetes and the metabolic syndrome...
  43. ncbi Identification and characterization of members of the FKHR (FOX O) subclass of winged-helix transcription factors in the mouse
    W H Biggs
    Ludwig Institute for Cancer Research, San Diego Branch, La Jolla, California 92093 0660, USA
    Mamm Genome 12:416-25. 2001
    Genetic alterations of FKHR (FOXO1), AF6q21 (FOXO2), and AFX (FOXO4), closely related members of the forkhead family of DNA binding proteins, in human cancers has suggested they play a role in the regulation of cellular differentiation ..
  44. ncbi The forkhead transcription factor AFX activates apoptosis by induction of the BCL-6 transcriptional repressor
    Tracy Tzu Ling Tang
    Department of Molecular Oncology, Genentech, Inc, South San Francisco, California 94080, USA
    J Biol Chem 277:14255-65. 2002
    ..by the inhibition of genetic programs induced by a subfamily of forkhead transcription factors including AFX. Here we describe an AFX-regulated pathway that appears to account for at least part of this apoptotic regulatory ..
  45. ncbi Expression of FKHR, FKHRL1, and AFX genes in the rodent ovary: evidence for regulation by IGF-I, estrogen, and the gonadotropins
    JoAnne S Richards
    Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    Mol Endocrinol 16:580-99. 2002
    ..box binding protein (Foxo1), FKHRL1 (Forkhead-like protein-1 = Foxo3), and AFX (a Forkhead transcription factor = Foxo4); all defined according to the Human and Mouse Gene Nomenclature Committee) are expressed in the rodent ovary and ..
  46. ncbi FOXO forkhead transcription factors induce G(2)-M checkpoint in response to oxidative stress
    Yoko Furukawa-Hibi
    Department of Geriatric Research, National Institute for Longevity Sciences, 36 3 Gengo, Morioka, Obu, Aichi 474 8522, Japan
    J Biol Chem 277:26729-32. 2002
    Members of the FOXO family of mammalian forkhead transcription factors, including AFX, FKHRL1, and FKHR, are homologs of DAF-16, which regulates genes that contribute both to longevity and to resistance to various stresses (including ..
  47. pmc MLL-AFX requires the transcriptional effector domains of AFX to transform myeloid progenitors and transdominantly interfere with forkhead protein function
    Chi Wai So
    Department of Pathology, Stanford University School of Medicine, California 94305, USA
    Mol Cell Biol 22:6542-52. 2002
    MLL-AFX is a fusion gene created by t(X;11) chromosomal translocations in a subset of acute leukemias of either myeloid or lymphoid derivation...
  48. ncbi Common mechanism for oncogenic activation of MLL by forkhead family proteins
    Chi Wai So
    Department of Pathology, Stanford University School of Medicine, CA 94305, USA
    Blood 101:633-9. 2003
    ..of these partner genes code for members of the forkhead subfamily of transcription factors designated FKHRL1 and AFX. We demonstrate here that MLL-FKHRL1 enhances the self-renewal of murine myeloid progenitors in vitro and induces ..
  49. pmc Disruption of forkhead transcription factor (FOXO) family members in mice reveals their functional diversification
    Taisuke Hosaka
    Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093 0660, USA
    Proc Natl Acad Sci U S A 101:2975-80. 2004
    ..of DAF-16, the closely-related FOXO subclass of forkhead transcription factors (FKHR/FOXO1, FKHRL1/FOXO3a, and AFX/FOXO4), also have important roles in cell cycle arrest, apoptosis and stress responses in vitro, but their in vivo ..
  50. ncbi Phenotypic modulation of smooth muscle cells through interaction of Foxo4 and myocardin
    Zhi Ping Liu
    Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA
    Dev Cell 9:261-70. 2005
    ..We show that Foxo4 represses SMC differentiation by interacting with and inhibiting the activity of myocardin, a transcriptional ..
  51. ncbi Receptor activator of NF-kappaB (RANK) cytoplasmic motif, 369PFQEP373, plays a predominant role in osteoclast survival in part by activating Akt/PKB and its downstream effector AFX/FOXO4
    Wei Liu
    Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
    J Biol Chem 280:43064-72. 2005
    ..has been shown to utilize distinct downstream effectors (glycogen synthase kinase-3beta, FKHR/FOXO1a, BAD, and AFX/FOXO4) to regulate cell survival, we next determined which downstream effector(s) is activated by Akt/PKB to promote ..
  52. ncbi Spatial and temporal expression of FoxO transcription factors in the developing and adult murine brain
    Marco F M Hoekman
    Department of Pharmacology and Anatomy, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    Gene Expr Patterns 6:134-40. 2006
    ..5 and E14. In summary, the presented data show FoxO factors to be expressed in the adult and developing mouse brain, in a spatially end temporally restricted manner...
  53. ncbi Identification of forkhead transcription factors in cortical and dopaminergic areas of the adult murine brain
    Patrick J E C Wijchers
    Rudolf Magnus Institute of Neuroscience, Department of Pharmacology and Anatomy, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    Brain Res 1068:23-33. 2006
    ..These forkhead transcription factors may play a role in maintenance and survival of developing and adult neurons...
  54. pmc FoxO4 regulates tumor necrosis factor alpha-directed smooth muscle cell migration by activating matrix metalloproteinase 9 gene transcription
    Hao Li
    Department of Internal Medicine, University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd, Dallas, TX 75390 9148, USA
    Mol Cell Biol 27:2676-86. 2007
    ..In this study, we show that FoxO4 activates transcription of the MMP9 gene in response to tumor necrosis factor alpha (TNF-alpha) signaling...
  55. ncbi FoxOs in tumor suppression and stem cell maintenance
    Karen C Arden
    Ludwig Institute for Cancer Research and Department of Medicine, University of California, San Diego, School of Medicine, La Jolla, CA 92093, USA
    Cell 128:235-7. 2007
    ..Demonstrate that FoxOs are critical for the long-term maintenance of hematopoietic stem cells, and show that FoxOs suppress the formation of hemangiomas and lymphomas in mice...
  56. pmc FoxO transcription factors suppress Myc-driven lymphomagenesis via direct activation of Arf
    Caroline Bouchard
    Institute of Molecular Biology and Tumor Research, 35033 Marburg, Germany
    Genes Dev 21:2775-87. 2007
    ..These data demonstrate that FoxO factors mediate Myc-induced Arf expression and provide direct genetic evidence for their tumor-suppressive capacity...
  57. pmc AKT/FOXO signaling enforces reversible differentiation blockade in myeloid leukemias
    Stephen M Sykes
    Center for Regenerative Medicine and Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA
    Cell 146:697-708. 2011
    ..These data reveal a molecular role for AKT/FOXO and JNK/c-JUN in maintaining a differentiation blockade that can be targeted to inhibit leukemias with a range of genetic lesions...
  58. doi Regulation of cardiomyocyte proliferation and myocardial growth during development by FOXO transcription factors
    Heather J Evans-Anderson
    Division of Molecular Cardiovascular Biology, Cincinnati Children s Hospital Medical Center, Ohio 45229, USA
    Circ Res 102:686-94. 2008
    ..These data support FOXO transcription factors as negative regulators of cardiomyocyte proliferation and promoters of neonatal cell cycle withdrawal during heart development...
  59. doi FOXO transcription factors are mechanosensitive and their regulation is altered with aging in the respiratory pump
    Patricia S Pardo
    Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA
    Am J Physiol Cell Physiol 294:C1056-66. 2008
    ..We investigated the effects of diaphragm stretch on three FOXO isoforms, Foxo1, Foxo3a, and Foxo4, in normal mice at different ages...
  60. doi Control of thrombin signaling through PI3K is a mechanism underlying plasticity between hair follicle dermal sheath and papilla cells
    Anne Catherine Feutz
    Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
    J Cell Sci 121:1435-43. 2008
    ..Our results indicate that control of thrombin signaling interferes with hair follicle dermal cells plasticity to regulate their function...
  61. pmc Mdm2 induces mono-ubiquitination of FOXO4
    Arjan B Brenkman
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands
    PLoS ONE 3:e2819. 2008
    ..For example, the de-ubiquitinating enzyme USP7 removes ubiquitin from both FOXO and p53. However, Skp2 has been identified as E3 ligase for FOXO1, whereas Mdm2 is the prime E3 ligase for p53...
  62. pmc TNF induction of atrogin-1/MAFbx mRNA depends on Foxo4 expression but not AKT-Foxo1/3 signaling
    Jennifer S Moylan
    Department of Physiology, University of Kentucky, Lexington, Kentucky 40536 0298, USA
    Am J Physiol Cell Physiol 295:C986-93. 2008
    ..TNF has no effect on Foxo1/3 mRNA or Foxo1/3 nuclear localization. Instead, TNF increases nuclear Foxo4 protein (+55%)...
  63. doi Overexpression of the transcription factor Foxo4 is associated with rapid glucose clearance
    Biao Wang
    Department of Laboratory Medicine, University of California, San Francisco, CA 94107, USA
    Mol Cell Endocrinol 307:217-23. 2009
    ..In this communication, we show that LepTg mice overexpress the forkhead transcription factor foxo4 in their remnant adipose tissue...
  64. pmc FoxO4 inhibits NF-kappaB and protects mice against colonic injury and inflammation
    Wen Zhou
    Departmentsof Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9148, USA
    Gastroenterology 137:1403-14. 2009
    b>FoxO4 is a member of the forkhead box transcription factor O (FoxO) subfamily. FoxO proteins are involved in diverse biological processes...
  65. doi FOXO transcription factors enforce cell cycle checkpoints and promote survival of hematopoietic cells after DNA damage
    Hong Lei
    Department of Pharmacology, The University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA
    Mol Cancer Res 7:1294-303. 2009
    ..Inhibition of FOXO activity by cytokine-induced PI3K/AKT signaling is sufficient to override these DNA damage-induced cell cycle checkpoints, but may negatively impact hematopoietic cell viability...
  66. doi Fhl2 interacts with Foxk1 and corepresses Foxo4 activity in myogenic progenitors
    Xiaozhong Shi
    Lillehei Heart Institute, University of Minnesota Twin Cities, Minneapolis, Minnesota 55455, USA
    Stem Cells 28:462-9. 2010
    ..assays, we observed that Fhl2, in a dose-dependent fashion, promotes Foxk1 transcriptional repression of Foxo4 activity...
  67. doi The DNA damage repair protein Ku70 interacts with FOXO4 to coordinate a conserved cellular stress response
    Arjan B Brenkman
    Department of Physiological Chemistry, University Medical Centre Utrecht, Utrecht, The Netherlands
    FASEB J 24:4271-80. 2010
    In this study, we searched for proteins regulating the tumor suppressor and life-span regulator FOXO4. Through an unbiased tandem-affinity purification strategy combined with mass spectrometry, we identified the heterodimer Ku70/Ku80 (Ku)..
  68. doi Inactivation of fibroblast growth factor binding protein 3 causes anxiety-related behaviors
    Yasunari Yamanaka
    Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto 606 8507, Japan
    Mol Cell Neurosci 46:200-12. 2011
    ..Therefore, FGF-BP3 plays a critical role in the regulation of emotional states and in the development of anxiety disorders and should be investigated as a therapeutic target for anxiety disease in humans...
  69. pmc FoxOs enforce a progression checkpoint to constrain mTORC1-activated renal tumorigenesis
    Boyi Gan
    Belfer Institute for Applied Cancer Science, Boston, MA 02115, USA
    Cancer Cell 18:472-84. 2010
    ....
  70. pmc Identification of the differential distribution patterns of mRNAs and consensus binding sequences for mouse DAF-16 homologues
    T Furuyama
    Laboratory of Genetics of Aging, Department of Molecular Genetic Research, National Institute for Longevity Sciences NILS, 36 3 Gengo, Morioka, Oobu, Aichi 474 8522, Japan
    Biochem J 349:629-34. 2000
    ..Mammalian DAF-16 homologues include AFX, FKHR and FKHRL1, which contain a conserved forkhead domain and three putative phosphorylation sites for the Ser/..
  71. pmc β-Catenin-dependent FGF signaling sustains cell survival in the anterior embryonic head by countering Smad4
    Hunki Paek
    Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Dev Cell 20:689-99. 2011
    ..Moreover, these antagonistic pathways converge on the transcriptional regulation of apoptosis, and genes such as Cdkn1a, suggesting a mechanism for how signaling centers in the embryonic head regulate cell survival...
  72. pmc Foxo1 is required in mouse spermatogonial stem cells for their maintenance and the initiation of spermatogenesis
    Meredith J Goertz
    Department of Pathology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, Texas 75390 9072, USA
    J Clin Invest 121:3456-66. 2011
    ..Combined deficiency of Foxo1, Foxo3, and Foxo4 resulted in a severe impairment of SSC self-renewal and a complete block of differentiation, indicating that Foxo3 ..
  73. ncbi Analysis of expansion of myeloid progenitors in mice to identify leukemic susceptibility genes
    Vincent E Sollars
    Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, 233 South 10th Street, Philadelphia, Pennsylvania 19107, USA
    Mamm Genome 17:808-21. 2006
    ..Given the importance of this cell compartment in leukemia progression and the soon to be released genomic sequence of 15 mouse strains, these differences may provide a valuable tool for research into leukemia...

Research Grants5

  1. Convergence of Nuclear Receptor and Forkhead Signaling
    Paul Dowell; Fiscal Year: 2004
    ..The excellent research environment at Johns Hopkins coupled with an extensive collaborative team of experts in relevant fields of study is ideal for successful completion of the proposed work. ..
  2. LH ACTION IN OVARIAN CELL DIFFERENTIATION
    Joanne Richards; Fiscal Year: 2007
    ..A related and longer term goal of the research is to identify and characterize the genes regulated by LH, prostaglandins (PGs), and C/EBPs that control key steps in the ovulatory process. ..
  3. Ovarian Follicular Developmental and Hormone Action
    Joanne Richards; Fiscal Year: 2007
    ..3) Determine the molecular, cellular and hormonal basis of the altered ovarian phenotype of the TAFII105 null mice. 4) Determine the function of Wnt-4 in the adult ovary. ..
  4. LH ACTION IN OVARIAN CELL DIFFERENTIATION
    Joanne Richards; Fiscal Year: 2008
    ..Specific Aim II: Determine the function of AREG target genes that are uniquely expressed at high levels in ovulated COCs (compared to granulosa cells) and that impact ovulation. ..
  5. Role of FOXO4 in atherosclerosis
    Zhi Ping Liu; Fiscal Year: 2010
    ..Recently, we identified a novel transcriptional mechanism by which FOXO4 regulates smooth muscle cell (SMC) phenotypes and transcription of matrix metalloproteinase 9 (MMP9) and Toll-like-..