4E-BP1

Summary

Gene Symbol: 4E-BP1
Description: eukaryotic translation initiation factor 4E binding protein 1
Alias: 4E-BP1, 4EBP1, BP-1, PHAS-I, eIF4E-binding protein 1, eukaryotic translation initiation factor 4E-binding protein 1, phosphorylated heat- and acid-stable protein regulated by insulin 1
Species: human

Top Publications

  1. ncbi Adenovirus-mediated eukaryotic initiation factor 4E binding protein-1 in combination with rapamycin inhibits tumor growth of pancreatic ductal adenocarcinoma in vivo
    Roshan Mishra
    Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060 8638, Japan
    Int J Oncol 34:1231-40. 2009
  2. ncbi Phosphorylation of 4E-BP by LRRK2 affects the maintenance of dopaminergic neurons in Drosophila
    Yuzuru Imai
    Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan
    EMBO J 27:2432-43. 2008
  3. ncbi Hierarchical phosphorylation of the translation inhibitor 4E-BP1
    A C Gingras
    Department of Biochemistry and McGill Cancer Centre, McGill University, Montreal, Quebec H3G 1Y6, Canada
    Genes Dev 15:2852-64. 2001
  4. ncbi 4E-binding protein 1: a key molecular "funnel factor" in human cancer with clinical implications
    Gemma Armengol
    Department of Pathology, Vall d Hebron University Hospital, Barcelona, Spain
    Cancer Res 67:7551-5. 2007
  5. ncbi 4E-binding protein 1, a cell signaling hallmark in breast cancer that correlates with pathologic grade and prognosis
    Federico Rojo
    Department of Pathology, Vall d Hebron University Hospital, Barcelona, Spain
    Clin Cancer Res 13:81-9. 2007
  6. ncbi Repression of cap-dependent translation by 4E-binding protein 1: competition with p220 for binding to eukaryotic initiation factor-4E
    A Haghighat
    Department of Biochemistry, McGill University, Montreal, Quebec, Canada
    EMBO J 14:5701-9. 1995
  7. ncbi PRAS40 is a target for mammalian target of rapamycin complex 1 and is required for signaling downstream of this complex
    Bruno D Fonseca
    Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
    J Biol Chem 282:24514-24. 2007
  8. ncbi Insulin-stimulated kinase from rat fat cells that phosphorylates initiation factor 4E-binding protein 1 on the rapamycin-insensitive site (serine-111)
    K J Heesom
    Department of Biochemistry, University of Bristol, School of Medical Sciences, Bristol, Avon BS81TD, UK
    Biochem J 336:39-48. 1998
  9. ncbi Phosphorylated 4E binding protein 1: a hallmark of cell signaling that correlates with survival in ovarian cancer
    Josep Castellvi
    Department of Pathology, Vall d Hebron University Hospital, Barcelona, Spain
    Cancer 107:1801-11. 2006
  10. ncbi Target of rapamycin (TOR)-signaling and RAIP motifs play distinct roles in the mammalian TOR-dependent phosphorylation of initiation factor 4E-binding protein 1
    Anne Beugnet
    Division of Molecular Physiology, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom
    J Biol Chem 278:40717-22. 2003

Research Grants

  1. Alcohol Consumption and Risk of NHL: Role of MTOR Dysfunction
    Ronald Gartenhaus; Fiscal Year: 2009
  2. Alcohol Consumption and Risk of NHL: Role of MTOR Dysfunction
    RONALD BENJAMIN GARTENHAUS; Fiscal Year: 2010
  3. Role of 4E-BP1 and 4E-BP2 in Translational Control
    Laura Beretta; Fiscal Year: 2006
  4. Amino Acids and Muscle Protein Synthesis
    Robert Wolfe; Fiscal Year: 2006
  5. Antifibrotic Drug Discovery in Acute Lung Injury
    Peter Bitterman; Fiscal Year: 2007
  6. GENES REGULATED BY C MYC
    Emmett Schmidt; Fiscal Year: 2004
  7. STRUCTURAL BASIS OF TRANSLATION INITIATION BY EIF-4E
    Gerhard Wagner; Fiscal Year: 2000
  8. INSULIN ACTION IN MUSCLE AND FAT CELL
    John Lawrence; Fiscal Year: 2000
  9. Nuclear Reprogramming and Phenotype in Cloned Embryos
    Keith E Latham; Fiscal Year: 2010
  10. Nuclear Reprogramming and Phenotype in Cloned Embryos
    Keith E Latham; Fiscal Year: 2010

Detail Information

Publications151 found, 100 shown here

  1. ncbi Adenovirus-mediated eukaryotic initiation factor 4E binding protein-1 in combination with rapamycin inhibits tumor growth of pancreatic ductal adenocarcinoma in vivo
    Roshan Mishra
    Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060 8638, Japan
    Int J Oncol 34:1231-40. 2009
    ..Combination therapy with rapamycin significantly inhibited proliferation and tumor growth in vitro as well as in vivo. Therefore, combination of Ad 4E-BP1 and rapamycin may be a more effective adjuvant therapy...
  2. ncbi Phosphorylation of 4E-BP by LRRK2 affects the maintenance of dopaminergic neurons in Drosophila
    Yuzuru Imai
    Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan
    EMBO J 27:2432-43. 2008
    ..Our results suggest that chronic inactivation of 4E-BP by LRRK2 with pathogenic mutations deregulates protein translation, eventually resulting in age-dependent loss of DA neurons...
  3. ncbi Hierarchical phosphorylation of the translation inhibitor 4E-BP1
    A C Gingras
    Department of Biochemistry and McGill Cancer Centre, McGill University, Montreal, Quebec H3G 1Y6, Canada
    Genes Dev 15:2852-64. 2001
    ..Finally, we show that phosphorylation of Ser 65 and Thr 70 alone is insufficient to block binding to eIF4E, indicating that a combination of phosphorylation events is necessary to dissociate 4E-BP1 from eIF4E...
  4. ncbi 4E-binding protein 1: a key molecular "funnel factor" in human cancer with clinical implications
    Gemma Armengol
    Department of Pathology, Vall d Hebron University Hospital, Barcelona, Spain
    Cancer Res 67:7551-5. 2007
    ..Further investigation into this concept may identify additional funnel factors in the oncogenic pathways and provide potential therapeutic targets...
  5. ncbi 4E-binding protein 1, a cell signaling hallmark in breast cancer that correlates with pathologic grade and prognosis
    Federico Rojo
    Department of Pathology, Vall d Hebron University Hospital, Barcelona, Spain
    Clin Cancer Res 13:81-9. 2007
    ....
  6. ncbi Repression of cap-dependent translation by 4E-binding protein 1: competition with p220 for binding to eukaryotic initiation factor-4E
    A Haghighat
    Department of Biochemistry, McGill University, Montreal, Quebec, Canada
    EMBO J 14:5701-9. 1995
    ..Thus, translational control by growth factors, insulin and mitogens is affected by changes in the relative affinities of 4E-BP1 and p220 for eIF-4E...
  7. ncbi PRAS40 is a target for mammalian target of rapamycin complex 1 and is required for signaling downstream of this complex
    Bruno D Fonseca
    Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
    J Biol Chem 282:24514-24. 2007
    ..However, this has no effect on the phosphorylation of Akt or TSC2 (an Akt substrate). These data place PRAS40 downstream of mTORC1 but upstream of its effectors, such as S6K1 and 4E-BP1...
  8. ncbi Insulin-stimulated kinase from rat fat cells that phosphorylates initiation factor 4E-binding protein 1 on the rapamycin-insensitive site (serine-111)
    K J Heesom
    Department of Biochemistry, University of Bristol, School of Medical Sciences, Bristol, Avon BS81TD, UK
    Biochem J 336:39-48. 1998
    ....
  9. ncbi Phosphorylated 4E binding protein 1: a hallmark of cell signaling that correlates with survival in ovarian cancer
    Josep Castellvi
    Department of Pathology, Vall d Hebron University Hospital, Barcelona, Spain
    Cancer 107:1801-11. 2006
    ..and extracellular regulated kinase (ERK) pathways and by some downstream molecules, such as 4E binding protein 1 (4EBP1), eukaryotic initiation factor 4E, and p70 ribosomal protein S6 kinase (p70S6K)...
  10. ncbi Target of rapamycin (TOR)-signaling and RAIP motifs play distinct roles in the mammalian TOR-dependent phosphorylation of initiation factor 4E-binding protein 1
    Anne Beugnet
    Division of Molecular Physiology, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom
    J Biol Chem 278:40717-22. 2003
    ..The RAIP motif thus promotes the mTOR-dependent phosphorylation of multiple sites in 4E-BP1 independently of the 4E-BP1/raptor interaction...
  11. ncbi Structure of S6 kinase 1 determines whether raptor-mTOR or rictor-mTOR phosphorylates its hydrophobic motif site
    Siraj M Ali
    Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Department of Biology, Cambridge, 02142, USA
    J Biol Chem 280:19445-8. 2005
    ..Because many members of the AGC family of kinases lack an analogous domain, rictor-mTOR may phosphorylate the hydrophobic motifs of other kinases...
  12. ncbi Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling
    Andrew R Tee
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 99:13571-6. 2002
    ....
  13. ncbi Regulation of 4E-BP1 phosphorylation: a novel two-step mechanism
    A C Gingras
    Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, Quebec, H3G 1Y6, Canada
    Genes Dev 13:1422-37. 1999
    ..Taken together, our results suggest that 4E-BP1 phosphorylation by FRAP/mTOR on Thr-37 and Thr-46 is a priming event for subsequent phosphorylation of the carboxy-terminal serum-sensitive sites...
  14. ncbi The C terminus of initiation factor 4E-binding protein 1 contains multiple regulatory features that influence its function and phosphorylation
    Xuemin Wang
    Division of Molecular Physiology, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom
    Mol Cell Biol 23:1546-57. 2003
    ..However, in 4E-BP3, replacement of the alanine at the position corresponding to S112 by serine or glutamate did not confer the ability to be released from eIF4E in response to insulin...
  15. ncbi Participation of ATM in insulin signalling through phosphorylation of eIF-4E-binding protein 1
    D Q Yang
    Department of Hematology Oncology, St Jude Children s Research Hospital, 332 North Lauderdale Street, Memphis, Tennessee 38105 2794, USA
    Nat Cell Biol 2:893-8. 2000
    ..Through this mechanism, a lack of ATM activity probably contributes to some of the metabolic abnormalities, such as poor growth and insulin resistance, reported in ataxia telangiectasia cells and patients with ataxia telangiectasia...
  16. ncbi Tissue distribution, genomic structure, and chromosome mapping of mouse and human eukaryotic initiation factor 4E-binding proteins 1 and 2
    K Tsukiyama-Kohara
    Department of Biochemistry, McGill University, Montreal, Quebec, H3G 1Y6, Canada
    Genomics 38:353-63. 1996
    ..Mouse 4E-BP1 and 4E-BP2 map to chromosomes 8 (A4-B1) and 10 (B4-B5), respectively, and human 4E-BP1 and 4E-BP2 localize to chromosomes 8p12 and 10q21-q22, respectively...
  17. ncbi Analysis of the regulatory motifs in eukaryotic initiation factor 4E-binding protein 1
    Vivian H Y Lee
    Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada
    FEBS J 275:2185-99. 2008
    ..These data provide important information on the structural requirements for efficient signalling downstream of mTORC1...
  18. ncbi Cell cycle-dependent phosphorylation of the translational repressor eIF-4E binding protein-1 (4E-BP1)
    K J Heesom
    University of Bristol, Department of Biochemistry, School of Medical Sciences, University Walk, BS8 1TD, Bristol, United Kingdom
    Curr Biol 11:1374-9. 2001
    ..Crucially, the increased phosphorylation of 4E-BP1 during mitosis results in its complete dissociation from eIF-4E...
  19. ncbi Regulation of cyclin D1 expression by mTORC1 signaling requires eukaryotic initiation factor 4E-binding protein 1
    J Averous
    Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada
    Oncogene 27:1106-13. 2008
    ....
  20. ncbi Binding preference of eIF4E for 4E-binding protein isoform and function of eIF4E N-terminal flexible region for interaction, studied by SPR analysis
    Fumi Abiko
    Department of Physical Chemistry, Osaka University of Pharmaceutical Sciences, 4 20 1 Nasahara, Takatsuki, Osaka 569 1094, Japan
    Biochem Biophys Res Commun 355:667-72. 2007
    ....
  21. ncbi Regulation of the rapamycin and FKBP-target 1/mammalian target of rapamycin and cap-dependent initiation of translation by the c-Abl protein-tyrosine kinase
    V Kumar
    Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 275:10779-87. 2000
    ..These findings with the c-Abl tyrosine kinase represent the first demonstration of a negative physiologic regulator of RAFT1-mediated 5' cap-dependent translation...
  22. ncbi Caspase cleavage of initiation factor 4E-binding protein 1 yields a dominant inhibitor of cap-dependent translation and reveals a novel regulatory motif
    Andrew R Tee
    Division of Molecular Physiology, School of Life Sciences, Medical Sciences Institute, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, United Kingdom
    Mol Cell Biol 22:1674-83. 2002
    ..This suggests that the N-terminal sequence of 4E-BP1 is required for optimal regulation of 4E-BPs by insulin...
  23. ncbi The eIF4E-binding proteins 1 and 2 are negative regulators of cell growth
    D Rousseau
    Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, Quebec, Canada
    Oncogene 13:2415-20. 1996
    ..Thus, we demonstrate that the eIF4E-binding proteins act as negative regulators of cell growth. We propose that 4E-BPs are members of a class of negative regulators of cell growth acting on the translation machinery of the cell...
  24. ncbi Acute oral leucine administration stimulates protein synthesis during chronic sepsis through enhanced association of eukaryotic initiation factor 4G with eukaryotic initiation factor 4E in rats
    Thomas C Vary
    Department of Cellular and Molecular Physiology, Pennsylvania State University, College of Medicine, Hershey, PA 17033, USA
    J Nutr 137:2074-9. 2007
    ..We conclude that Leu stimulates a PKB-independent signal pathway elevating the eIF4G-eIF4E complex assembly through increased phosphorylation of eIF4G and decreased association of 4E-BP1 with eIF4E in skeletal muscle during sepsis...
  25. ncbi Possible mechanisms involved in the down-regulation of translation during transient global ischaemia in the rat brain
    C Martín De La Vega
    Departamento de Investigacion, Hospital Ramon y Cajal, Ctra Colmenar Km 9, 28034 Madrid, Spain
    Biochem J 357:819-26. 2001
    ....
  26. ncbi Vesicular stomatitis virus infection alters the eIF4F translation initiation complex and causes dephosphorylation of the eIF4E binding protein 4E-BP1
    John H Connor
    Department of Microbiology and Immunology, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA
    J Virol 76:10177-87. 2002
    ..This is the first noted modification of both eIF4E and 4E-BP1 phosphorylation levels among viruses that produce capped mRNA for protein translation...
  27. ncbi Thermal injury impairs cardiac protein synthesis and is associated with alterations in translation initiation
    Charles H Lang
    Department of Cellular and Molecular Physiology H166, Penn State College of Medicine, Hershey, PA 17033, USA
    Am J Physiol Regul Integr Comp Physiol 286:R740-50. 2004
    ....
  28. ncbi Nitric oxide mediates NMDA-induced persistent inhibition of protein synthesis through dephosphorylation of eukaryotic initiation factor 4E-binding protein 1 and eukaryotic initiation factor 4G proteolysis
    Valerie Petegnief
    Departamento de Isquemia Cerebral y Neurodegeneración, Instituto de Investigaciones Biomédicas de Barcelona, CSIC IDIBAPS, Rossello 161, Barcelona 08036, Spain
    Biochem J 411:667-77. 2008
    ..In conclusion, our data show that NO mediates NMDA-induced persistent translation inhibition and suggest that deficient eIF4F activity contributes to this process...
  29. ncbi Age-associated decrease in contraction-induced activation of downstream targets of Akt/mTor signaling in skeletal muscle
    Katsuhiko Funai
    Nutrition, Exercise Physiology, and Sarcopenia Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, 711 Washington St, Boston, MA 02111, USA
    Am J Physiol Regul Integr Comp Physiol 290:R1080-6. 2006
    ..These observations suggest that the anabolic response to muscle stimulation is attenuated with aging and may contribute to the limited capacity of hypertrophy in aged animals...
  30. ncbi Molecular cross-talk between MEK1/2 and mTOR signaling during recovery of 293 cells from hypertonic stress
    Susanne Naegele
    Biochemistry Laboratory, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QG, United Kingdom
    J Biol Chem 279:46023-34. 2004
    ....
  31. ncbi Oral leucine enhances myocardial protein synthesis in rats acutely administered ethanol
    Thomasc Vary
    Department of Cellular and Molecular Physiology, Penn State University College of Medicine, Hershey, PA 17033, USA
    J Nutr 139:1439-44. 2009
    ..of eIF4G(Ser(1108)) and a decreased assembly ( approximately 30%) of inactive eIF4E-binding protein1 (4EBP1).eIF4E complex in rats-administered ethanol. The reduced assembly of the 4EBP1...
  32. ncbi A potential role for extracellular signal-regulated kinases in prostaglandin F2alpha-induced protein synthesis in smooth muscle cells
    G N Rao
    Division of Cardiology, University of Texas Medical Branch, Galveston, Texas 77555, USA
    J Biol Chem 274:12925-32. 1999
    ....
  33. ncbi Activation of p53 stimulates proteasome-dependent truncation of eIF4E-binding protein 1 (4E-BP1)
    Constantina Constantinou
    Translational Control Group, Centre for Molecular and Metabolic Signalling, Division of Basic Medical Sciences, St George s, University of London, Cranmer Terrace, London SW17 0RE, U K
    Biol Cell 100:279-89. 2008
    ....
  34. ncbi Blocking eukaryotic initiation factor 4F complex formation does not inhibit the mTORC1-dependent activation of protein synthesis in cardiomyocytes
    Brandon P H Huang
    Department of Biochemistry and Molecular Biology, University of British Columbia and Diabetes Research Group, Life Sciences Institute, Vancouver, Canada
    Am J Physiol Heart Circ Physiol 296:H505-14. 2009
    ..Therefore, other mTORC1 targets are more important in the inhibition by rapamycin of the rapid activation of protein synthesis and of cell growth...
  35. ncbi Rapamycin limits formation of active eukaryotic initiation factor 4F complex following meal feeding in rat hearts
    Thomas C Vary
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    J Nutr 137:1857-62. 2007
    ..Furthermore, the rapamycin-sensitive reductions in phosphorylation of eIF4G may also lead to decreased formation of active eIF4G-eIF4E complex...
  36. ncbi New hierarchical phosphorylation pathway of the translational repressor eIF4E-binding protein 1 (4E-BP1) in ischemia-reperfusion stress
    María I Ayuso
    Department of Investigation, Hospital Ramon y Cajal, 28034 Madrid, Spain
    J Biol Chem 285:34355-63. 2010
    ..These data help to elucidate the physiological role of 4E-BP1 phosphorylation in controlling protein synthesis...
  37. ncbi IGF-I activates the eIF4F system in cardiac muscle in vivo
    Thomas C Vary
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Pennsylvania 17033, USA
    Mol Cell Biochem 272:209-20. 2005
    ..Furthermore, the results are consistent with a role for assembly of active eIF4G.eIF4E complex and activation of S6K1 in mediating the stimulation of mRNA translation initiation by IGF-I through a PKB/mTOR signaling pathway...
  38. ncbi Inactivation of eIF2B and phosphorylation of PHAS-I in heat-shocked rat hepatoma cells
    G C Scheper
    Department of Molecular Cell Biology, Utrecht University, 3584 CH Utrecht, The Netherlands
    J Biol Chem 272:26850-6. 1997
    ..Regulation of eIF2B activity appears to be the main mechanism to control translation initiation after heat shock at mild temperatures...
  39. ncbi Regulation of host translational machinery by African swine fever virus
    Alfredo Castello
    Centro de Biologia Molecular Severo Ochoa, CSIC UAM, Universidad Autonoma de Madrid, Madrid, Spain
    PLoS Pathog 5:e1000562. 2009
    ..Therefore, degradation of cellular polyadenylated mRNAs and recruitment of the translation machinery to viral factories may contribute to the inhibition of host protein synthesis, facilitating ASFV protein production in infected cells...
  40. ncbi Expression of the eukaryotic translation initiation factor 4E (eIF4E) and 4E-BP1 in esophageal cancer
    Zivar Salehi
    Department of Biology, Faculty of Sciences, The University of Guilan, Rasht, Iran
    Clin Biochem 39:404-9. 2006
    ..The aim of this study was to determine the level of expression of eIF4E and eIF4E-binding protein 1 (4E-BP1) in esophageal cancer...
  41. ncbi Developmental changes in the feeding-induced stimulation of translation initiation in muscle of neonatal pigs
    T A Davis
    Department of Pediatrics, United States Department of Agriculture Agricultural Research Service, Children s Nutrition Research Center, Baylor College of Medicine, Houston, Texas 77030, USA
    Am J Physiol Endocrinol Metab 279:E1226-34. 2000
    ..The results further suggest that the overall developmental decline in skeletal muscle protein synthesis involves regulation by eIF2B...
  42. ncbi Meal feeding enhances formation of eIF4F in skeletal muscle: role of increased eIF4E availability and eIF4G phosphorylation
    Thomas C Vary
    Department of Cellular and Molecular Physiology, Penn State University College of Medicine, Hershey, Pennsylvania 17033, USA
    Am J Physiol Endocrinol Metab 290:E631-42. 2006
    ..eIF4E complex assembly through increased phosphorylation of eIF4G and decreased association of 4E-BP1 with eIF4E...
  43. ncbi The embryonic pregnancy signal oestradiol influences gene expression at the level of translational initiation in porcine endometrial cells
    K Wollenhaupt
    Unit of Reproductive Biology, FBN Research Institute for the Biology of Farm Animals, Dummerstorf, Germany
    Reprod Domest Anim 42:167-75. 2007
    ..Therefore, embryonic oestrogens can potentially transmit their effect by influencing signalling cascades which modulate gene expression at the level of translational initiation...
  44. ncbi Impaired protein synthesis induced by acute alcohol intoxication is associated with changes in eIF4E in muscle and eIF2B in liver
    C H Lang
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey 17033 0850, USA
    Alcohol Clin Exp Res 24:322-31. 2000
    ..Acute alcohol intoxication in rats decreases protein synthesis in skeletal muscle and, to a lesser extent, in liver. The purpose of the present study was to examine potential mechanisms for the inhibitory effect of acute ethanol exposure...
  45. ncbi Eukaryotic initiation factors and protein synthesis after resistance exercise in rats
    P A Farrell
    Noll Physiological Research Center and Graduate Program in Physiology, Pennsylvania State University, University Park 16802, USA
    J Appl Physiol 88:1036-42. 2000
    ..eIF4E complexed to eIF4G (eIF4E x eIF4G), eIF4E binding protein 1 (4E-BP1) complexed to eIF4E, and phosphorylation state of eIF4E and 4E-BP1 (gamma-form) were assessed in ..
  46. ncbi Endotoxin disrupts the leucine-signaling pathway involving phosphorylation of mTOR, 4E-BP1, and S6K1 in skeletal muscle
    Charles H Lang
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    J Cell Physiol 203:144-55. 2005
    ..Hence, LPS working via a glucocorticoid-independent mechanism produces a leucine resistance in skeletal muscle that might be expected to impair the ability of this amino acid to stimulate translation initiation and protein synthesis...
  47. ncbi Sepsis-induced suppression of skeletal muscle translation initiation mediated by tumor necrosis factor alpha
    Charles H Lang
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    Metabolism 56:49-57. 2007
    ..Hence, the decreased constitutive protein synthesis observed in fast-twitch skeletal muscle in response to peritonitis is mediated by a TNF-dependent mechanism affecting mTOR regulation of translation initiation...
  48. ncbi Deficiency of dietary EAA preferentially inhibits mRNA translation of ribosomal proteins in liver of meal-fed rats
    T G Anthony
    Department of Cellular and Molecular Physiology, Pennsylvania State College of Medicine, Hershey, PA 17033, USA
    Am J Physiol Endocrinol Metab 281:E430-9. 2001
    ..Additionally, the translation of rp mRNAs is preferentially repressed in association with decreased S6K1 phosphorylation...
  49. ncbi Modulation of 4E-BP1 function as a critical determinant of enzastaurin-induced apoptosis
    Chad A Dumstorf
    Lilly Research Labs, Eli Lilly and Company, Indianapolis, Indiana 46285
    Mol Cancer Ther 9:3158-63. 2010
    ..Remarkably, enzastaurin-induced apoptosis was blocked in cancer cells depleted of 4E-BP1 by siRNAs, or in 4EBP1/2 knockout murine embryonic fibroblasts cells...
  50. ncbi 4E-BP3, a new member of the eukaryotic initiation factor 4E-binding protein family
    F Poulin
    Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, Quebec H3G 1Y6, Canada
    J Biol Chem 273:14002-7. 1998
    ..The overlapping function and expression of the different 4E-BP family members imply that there is redundancy in this translational control mechanism, underscoring its importance...
  51. ncbi Proteomic analysis of phosphoproteins sensitive to a phosphatidylinositol 3-kinase inhibitor, ZSTK474, by using SELDI-TOF MS
    Tetsuyuki Akashi
    Division of Molecular Pharmacology, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan
    Proteome Sci 7:14. 2009
    ..CONCLUSION: We identified a group of ZSTK474-sensitive phosphoproteins as the multi-phosphorylated form of 4E-BP1 by combining IMAC, SELDI-TOF MS and antibodies...
  52. ncbi Activated eIF4E-binding protein slows G1 progression and blocks transformation by c-myc without inhibiting cell growth
    Mary Lynch
    Massachusetts General Hospital Cancer Center, Charlestown, Massachusetts 02129, USA
    J Biol Chem 279:3327-39. 2004
    ..approach in mammalian cells after identifying an autosensing mechanism that protects against increased levels of 4EBP1. Increased 4EBP1 induced a quantitative increase in the inactivated phosphorylated form of 4EBP1 in vitro and in ..
  53. ncbi Differential effect of sepsis on ability of leucine and IGF-I to stimulate muscle translation initiation
    Charles H Lang
    Department of Cellular and Molecular Physiology, H166, Pennsylvania State University College of Medicine, 500 University Dr, Hershey 17033, USA
    Am J Physiol Endocrinol Metab 287:E721-30. 2004
    ..Hence, sepsis produces a relatively specific Leu resistance in skeletal muscle that impairs the ability of this amino acid to stimulate translation initiation and protein synthesis...
  54. ncbi Effect of branched-chain amino acids on muscle atrophy in cancer cachexia
    Helen L Eley
    Nutritional Biomedicine, School of Life and Health Sciences, Aston University, Birmingham B4 7ET, UK
    Biochem J 407:113-20. 2007
    ..These changes would be expected to increase protein synthesis, whereas a reduction in the activation of PKR would be expected to attenuate the increased protein degradation...
  55. ncbi N-acetyl-cysteine abolishes hydrogen peroxide-induced modification of eukaryotic initiation factor 4F activity via distinct signalling pathways
    A O'Loghlen
    Servicio de Bioquimica, Departamento de Investigacion, Hospital Ramon y Cajal, Ctra Colmenar Km 9, 28034 Madrid, Spain
    Cell Signal 18:21-31. 2006
    ..Altogether our findings suggest that the effects caused by oxidative stress on eIF4s factors depends on two MAP kinase-independent signal transduction pathways, being at least one of them rapamycin-dependent...
  56. ncbi Striking multiplicity of eIF4E-BP1 phosphorylated isoforms identified by 2D gel electrophoresis regulation by heat shock
    R F Duncan
    School of Pharmacy, Department of Molecular Pharmacology and Toxicology, University of Southern California, Los Angeles, CA, USA
    Eur J Biochem 265:728-43. 1999
    ..These results identify a complex set of eIF4E-BP1 phosphorylation isoforms; changes in the expression of these isoforms in response to stresses such as heat shock may contribute to translation repression...
  57. ncbi Matrine inhibits the activity of translation factor eIF4E through dephosphorylation of 4E-BP1 in gastric MKN45 cells
    Tiejun Jiang
    Cancer Institute, Department of Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P R China
    Planta Med 73:1176-81. 2007
    ..These findings suggested that matrine inhibits the activity of eIF4E by dephosphorylating 4E-BP1, which partly counts for the growth inhibition in gastric MKN45 cells...
  58. ncbi Assessment of cell-signaling pathways in the regulation of mammalian target of rapamycin (mTOR) by amino acids in rat adipocytes
    P T Pham
    Department of Cellular and Molecular Physiology, The Pennsylvania State University, College of Medicine, Hershey, Pennsylvania 17033, USA
    J Cell Biochem 79:427-41. 2000
    ..Overall, our study emphasizes the need for caution when extending results obtained using established cell lines to the differentiated nondividing cells found in most tissues...
  59. ncbi Translational repression by human 4E-BP1 in yeast specifically requires human eIF4E as target
    J M Hughes
    Posttranscriptional Control Group, Department of Biomolecular Sciences, University of Manchester Institute of Science and Technology, P O Box 88, Manchester M60 1QD, United Kingdom
    J Biol Chem 274:3261-4. 1999
    ..Thus yeast eIF4E lacks structural features required for binding to human 4E-BP1. These results therefore demonstrate that the features of eIF4E required for binding to 4E-BP1 are distinct from those required for cap-complex assembly...
  60. ncbi Regulation of muscle protein synthesis during sepsis and inflammation
    Charles H Lang
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    Am J Physiol Endocrinol Metab 293:E453-9. 2007
    ....
  61. ncbi Implication of eIF2B rather than eIF4E in the regulation of global protein synthesis by amino acids in L6 myoblasts
    S R Kimball
    Department of Cellular and Molecular Physiology, The Pennsylvania State University, College of Medicine, Hershey, Pennsylvania 17033, USA
    J Biol Chem 273:30945-53. 1998
    ..Furthermore, under the conditions employed herein, alterations in eIF4E availability are not rate-controlling for global protein synthesis but might be necessary for regulation of translation of specific mRNAs...
  62. ncbi IGF-I and insulin regulate eIF4F formation by different mechanisms in muscle and liver in the ovine fetus
    Weihua Shen
    Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
    Am J Physiol Endocrinol Metab 283:E593-603. 2002
    ..Insulin regulates translation initiation via the PI 3-kinase-p70(S6k) pathway, whereas IGF-I does so mainly via mechanisms independent of the PI 3-kinase-p70(S6k) pathway...
  63. ncbi Alterations in interprotein interactions between translation initiation factors assessed by fluorescence resonance energy transfer
    S R Kimball
    Department of Cellular and Molecular Physiology, The Pennsylvania State University, College of Medicine, P O Box 850, Hershey, PA 17033, USA
    Int J Biochem Cell Biol 33:797-806. 2001
    ..Overall, the results demonstrate that fluorescence resonance energy transfer between EYFP--4E-BP1 and ECFP--eIF4E is a valuable tool in directly measuring alterations in the interaction of the two proteins...
  64. ncbi Molecular cloning and tissue distribution of PHAS-I, an intracellular target for insulin and growth factors
    C Hu
    Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, MO 63110
    Proc Natl Acad Sci U S A 91:3730-4. 1994
    ..However, in view of its tissue distribution and the fact that the protein is phosphorylated in response to insulin, we speculate that PHAS-I is important in insulin action...
  65. ncbi [Blockage of mTOR signaling pathway by rapamycin contributes to inhibition of tumor cell proliferation in ALK-positive lymphoid cell strains]
    Ling Gu
    Laboratory of Hematology, West China Hospital, Sichuan University, Chengdu 610041, China
    Zhonghua Xue Ye Xue Za Zhi 29:662-6. 2008
    ..To investigate the relationship between mTOR signaling pathway and ALK-positive lymphoid cell lines...
  66. ncbi Inhibition of 4E-BP1 sensitizes U87 glioblastoma xenograft tumors to irradiation by decreasing hypoxia tolerance
    Ludwig Dubois
    Department of Radiation Oncology Maastro Laboratory, GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands
    Int J Radiat Oncol Biol Phys 73:1219-27. 2009
    ..However, although 4E-BP1 harbors anti-growth activity, its expression is paradoxically elevated in some tumors. The aim of this study was to investigate the functional role of 4E-BP1 in the context of solid tumors...
  67. ncbi Local control of a disorder-order transition in 4E-BP1 underpins regulation of translation via eIF4E
    Shirley Tait
    Manchester Interdisciplinary Biocentre, University of Manchester, 131 Princess Street, Manchester M1 7DN, United Kingdom
    Proc Natl Acad Sci U S A 107:17627-32. 2010
    ..This type of order-disorder regulatory mechanism is likely to be relevant to other intermolecular regulatory phenomena in the cell...
  68. ncbi Amino acids regulate skeletal muscle PHAS-I and p70 S6-kinase phosphorylation independently of insulin
    W Long
    Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA
    Am J Physiol Endocrinol Metab 279:E301-6. 2000
    ..This effect is not dependent on increases in plasma insulin and simulates the activation of protein synthesis that accompanies normal feeding...
  69. ncbi eIF4E knockdown decreases breast cancer cell growth without activating Akt signaling
    Alpana Soni
    Department of Surgical Oncology, The University of Texas M D Anderson Cancer Center, Unit 444, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Mol Cancer Ther 7:1782-8. 2008
    ..Unlike rapamycin and its analogues, eIF4E knockdown is not associated with Akt activation...
  70. ncbi eIF4E activation is commonly elevated in advanced human prostate cancers and significantly related to reduced patient survival
    Jeremy R Graff
    Lilly Research Labs, Eli Lilly and Company, Indianapolis, Indiana 46285, USA
    Cancer Res 69:3866-73. 2009
    ..Collectively, these data implicate eIF4E activation in prostate cancer and suggest that targeting eIF4E may be attractive for prostate cancer therapy...
  71. ncbi 4E binding protein 1 expression is inversely correlated to the progression of gastrointestinal cancers
    M E Martin
    Departamento de Bioquimica y Biologia Molecular, Universidad de Alcala, Alcala de Henares, 28871, Madrid, Spain
    Int J Biochem Cell Biol 32:633-42. 2000
    ..Our results support a possible role of 4E-BP1 as a prognostic factor in gastrointestinal carcinoma...
  72. ncbi Phosphorylation of the eIF4E-binding protein PHAS-I after exposure of PC12 cells to EGF and NGF
    M Kleijn
    Utrecht University, Department of Molecular Cell Biology, The Netherlands
    FEBS Lett 396:165-71. 1996
    ..Apparently, PHAS-I was phosphorylated in a PI-3 kinase-, PKC-, and FRAP-dependent manner after EGF or NGF stimulation. Only PI-3 kinase and FRAP are involved in the regulation of the basal level of PHAS-I phosphorylation...
  73. ncbi The interaction of eIF4E with 4E-BP1 is an induced fit to a completely disordered protein
    C M Fletcher
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Protein Sci 7:1639-42. 1998
    ..This implies that 4E-BP1 has no regions of local order in the absence of eIF4E. The interaction therefore appears to be an induced fit to a completely disordered protein molecule...
  74. ncbi FOXO1 regulates the expression of 4E-BP1 and inhibits mTOR signaling in mammalian skeletal muscle
    Robert J Southgate
    Cellular and Molecular Metabolism Laboratory, The Baker Heart Research Institute, Commercial Road, Melbourne 3004, Victoria, Australia
    J Biol Chem 282:21176-86. 2007
    ..These data suggest that FOXO1 may be an important therapeutic target for human diseases where anabolism is impaired...
  75. ncbi Expression of selected tumor suppressor and oncogenes in endometrium of women with endometriosis
    P Laudanski
    Department of Perinatology, Medical University of Bialystok, ul Marii Sklodowskiej Curie 24a, Bialystok, Poland
    Hum Reprod 24:1880-90. 2009
    ..The aim of the study was to compare the expression level of mammalian target of rapamycin (mTOR) tumor suppressor and oncogene-related genes in the endometrium of women with and without endometriosis as well as in ovarian endometriosis...
  76. ncbi Effects of ovarian steroids and epidermal growth factor (EGF) on expression and bioactivation of specific regulators of transcription and translation in oviductal tissue in pigs
    K Wollenhaupt
    Unit of Reproductive Biology, Research Institute for Biology of Farm Animals, 18196 Dummerstorf, Germany
    Reproduction 123:87-96. 2002
    ..The effect of oestrogen and EGF in reducing the mobility of 4E-BP1 on gels in oviductal explants indicates that EGF may mediate the effect of oestradiol in the oviducts...
  77. ncbi Oral administration of leucine stimulates phosphorylation of 4E-bP1 and S6K 1 in skeletal muscle but not in liver of diabetic rats
    Fumiaki Yoshizawa
    Department of Animal Science, Faculty of Agriculture, Utsunomiya University, Tochigi, Japan
    J Nutr Sci Vitaminol (Tokyo) 48:59-64. 2002
    ..In contrast to skeletal muscle, insulin is essential in mediating the leucine-dependent induction of 4E-BP1 and S6K1 phosphorylation in liver. leucine, 4E-BP1, S6K1, translation initiation, diabetes..
  78. ncbi Biophysical studies of eIF4E cap-binding protein: recognition of mRNA 5' cap structure and synthetic fragments of eIF4G and 4E-BP1 proteins
    Anna Niedzwiecka
    Department of Biophysics, Institute of Experimental Physics, Warsaw University, 93 Zwirki and Wigury Street, 02 089 Warsaw, Poland
    J Mol Biol 319:615-35. 2002
    ..Phosphorylation of 4E-BP1 at Ser65 and Thr70 is insufficient to prevent binding to eIF4E. Enhancement of the eIF4E affinity for cap occurs after binding to eIF4G peptides...
  79. ncbi The splicing factor SF2/ASF regulates translation initiation by enhancing phosphorylation of 4E-BP1
    Gracjan Michlewski
    Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK
    Mol Cell 30:179-89. 2008
    ..Taken together, these data suggest a novel mechanism for the activation of translation initiation of a subset of mRNAs bound by the shuttling protein SF2/ASF...
  80. ncbi [The expression of mammalian target of rapamycin and its substrates in autogenous vein graft in rats]
    Xin Hua Hu
    Department of Vascular Surgery, First Affiliated Hospital, China Medical University, Shenyang 110001, China
    Zhonghua Wai Ke Za Zhi 44:1053-7. 2006
    ..To investigate the expression of mammalian target of rapamycin (mTOR) and its substrates including p70s6k and 4E-BP1 in autogenous vein graft...
  81. ncbi Phosphorylation of PHAS-I by mitogen-activated protein (MAP) kinase. Identification of a site phosphorylated by MAP kinase in vitro and in response to insulin in rat adipocytes
    T A Haystead
    Department of Pharmacology, University of Virginia School of Medicine, Charlottesville 22903
    J Biol Chem 269:23185-91. 1994
    ..We conclude that PHAS-I is a substrate for MAP kinase both in vivo and in vitro. As PHAS-I is one of the most prominent insulin-stimulated phosphoproteins in adipocytes, it may qualify as the major MAP kinase substrate in these cells...
  82. ncbi The proline-rich Akt substrate of 40 kDa (PRAS40) is a physiological substrate of mammalian target of rapamycin complex 1
    Noriko Oshiro
    Biosignal Research Center, Kobe University, Kobe 657 8501, Japan
    J Biol Chem 282:20329-39. 2007
    ..Moreover, they indicate that the ability of raptor to bind endogenous substrates is limiting for the activity of mTORC1 in vivo and is therefore a potential locus of regulation...
  83. ncbi Structural and thermodynamic behavior of eukaryotic initiation factor 4E in supramolecular formation with 4E-binding protein 1 and mRNA cap analogue, studied by spectroscopic methods
    X Shen
    Department of Physical Chemistry, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan
    Chem Pharm Bull (Tokyo) 49:1299-303. 2001
    ..behavior of the complex formation of eIF4E with either or both mRNA cap analogue (m7GTP, m7GpppA, or m7GpppG) and 4EBP1 has been investigated by spectroscopic measurements...
  84. ncbi CCL5-mediated T-cell chemotaxis involves the initiation of mRNA translation through mTOR/4E-BP1
    Thomas T Murooka
    Division of Cellular and Molecular Biology, Toronto General Research Institute, University Health Network and Department of Immunology, University of Toronto, Toronto, ON, Canada
    Blood 111:4892-901. 2008
    ..Taken together, we describe a novel mechanism by which CCL5 influences translation of rapamycin-sensitive mRNAs and "primes" CD4(+) T cells for efficient chemotaxis...
  85. ncbi Regulation of cap-dependent translation initiation in the early stage porcine parthenotes
    Andrej Susor
    Institute of Animal Physiology and Genetics, Libechov, Czech Republic
    Mol Reprod Dev 75:1716-25. 2008
    ..Although the translation is gradually decreasing during early preimplantation development, the eIF4F complex, which is temporarily formed, might be a premise for the translation of a small subset of mRNAs at this period of development...
  86. ncbi Identification and function of the second eIF4E-binding region in N-terminal domain of eIF4G: comparison with eIF4E-binding protein
    Yu Umenaga
    Department of Physical Chemistry, Osaka University of Pharmaceutical Sciences, 4 20 1 Nasahara, Takatsuki, Osaka 569 1094, Japan
    Biochem Biophys Res Commun 414:462-7. 2011
    ..This clearly indicates the importance of the second binding region for the difference in function between eIF4G and 4E-BP for eIF4E translation...
  87. ncbi Amino acid availability and age affect the leucine stimulation of protein synthesis and eIF4F formation in muscle
    Jeffery Escobar
    USDA ARS Children s Nutrition Research Center, Dept of Pediatrics, Baylor College of Medicine, 1100 Bates St, Houston, TX 77030, USA
    Am J Physiol Endocrinol Metab 293:E1615-21. 2007
    ..Thus the ability of leucine to stimulate eIF4F formation and protein synthesis in skeletal muscle is dependent on AA availability and age...
  88. ncbi Glucocorticoids modulate amino acid-induced translation initiation in human skeletal muscle
    Zhenqi Liu
    Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Virginia Health System, Charlottesville, VA 22908 1410, USA
    Am J Physiol Endocrinol Metab 287:E275-81. 2004
    ....
  89. ncbi Control of the translational regulators PHAS-I and PHAS-II by insulin and cAMP in 3T3-L1 adipocytes
    T A Lin
    Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 271:30199-204. 1996
    ..In summary, our results indicate that PHAS-I and -II are controlled by the mammalian target of rapamycin and p70(S6K) signaling pathway and that in 3T3-L1 adipocytes this pathway is inhibited by increased cAMP...
  90. ncbi Paclitaxel induces the phosphorylation of the eukaryotic translation initiation factor 4E-binding protein 1 through a Cdk1-dependent mechanism
    Victoria L Greenberg
    Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, 800 Rose Street, Lexington, KY 40536, USA
    Oncogene 24:4851-60. 2005
    ..Taken together, our data suggest that PTX-increases the functional level of eIF-4E by promoting the hyperphosphorylation and release of 4E-BP1 through a cdk1-dependent mechanism...
  91. ncbi Dietary arginine supplementation increases mTOR signaling activity in skeletal muscle of neonatal pigs
    Kang Yao
    Laboratory of Animal Nutrition and Health, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan 410125, PR China
    J Nutr 138:867-72. 2008
    ..The findings provide a molecular mechanism for explaining the previous observation that increased circulating arginine stimulated muscle protein synthesis and promoted weight gain in neonatal pigs...
  92. ncbi Protein ingestion further augments S6K1 phosphorylation in skeletal muscle following resistance type exercise in males
    Rene Koopman
    Department of Movement Sciences, Nutrition and Toxicology Research Institute Maastricht NUTRIM, Maastricht University, Maastricht 6200 MD, The Netherlands
    J Nutr 137:1880-6. 2007
    ..45 +/- 0.07, P < 0.01) and remained elevated during recovery (P < 0.05). We conclude that the availability of dietary protein further enhances phosphorylation of S6K1 during recovery from resistance type exercise...
  93. ncbi PHAS proteins as mediators of the actions of insulin, growth factors and cAMP on protein synthesis and cell proliferation
    J C Lawrence
    Department of Pharmacology, University of Virginia School of Medicine, Charlottesville 22908, USA
    Adv Enzyme Regul 37:239-67. 1997
    ..Pharmacological and genetic evidence indicates that the mTOR/p70S6K pathway is involved in the control of PHAS-I and -II. Thus, PHAS proteins may be mediators of the effects of this pathway on protein synthesis and cell proliferation...
  94. ncbi Local insulin-like growth factor I prevents sepsis-induced muscle atrophy
    Gerald Nystrom
    Department of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University, Hershey, PA 17033, USA
    Metabolism 58:787-97. 2009
    ....
  95. ncbi Associations between multiple system atrophy and polymorphisms of SLC1A4, SQSTM1, and EIF4EBP1 genes
    Hiroyuki Soma
    Department of Neurology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
    Mov Disord 23:1161-7. 2008
    ..This study revealed genetic associations of SLC1A4, SQSTM1, and EIF4EBP1 with MSA. These results may lend genetic support to the hypothesis that oxidative stress is associated with the pathogenesis of MSA...
  96. ncbi Differential effects of insulin and dietary amino acids on muscle protein synthesis in adult and old rats
    Magali Prod'homme
    Institut National de la Recherche Agronomique et Centre de Recherche en Nutrition Humaine d Auvergne, Unité de Nutrition et Métabolisme Protéique, 63122 Saint Genes Champanelle, France
    J Physiol 563:235-48. 2005
    ..We concluded that insulin is required for the regulation of muscle protein synthesis irrespective of age and that the effect of dietary amino acids is blunted in old rats...
  97. ncbi TOS motif-mediated raptor binding regulates 4E-BP1 multisite phosphorylation and function
    Stefanie S Schalm
    The Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Curr Biol 13:797-806. 2003
    ..However, it is unclear how the TOS motif in S6K1 and 4E-BP1 mediates mTOR signaling...
  98. ncbi Overexpressed eIF4E is functionally active in surgical margins of head and neck cancer patients via activation of the Akt/mammalian target of rapamycin pathway
    Cherie Ann O Nathan
    Louisiana State University Health Sciences Center, Feist Weiller Cancer Center, Veterans Administration, Shreveport, Louisiana, USA
    Clin Cancer Res 10:5820-7. 2004
    ..We hypothesize that overexpressed eIF4E is functionally active in tumor margins through activation of the Akt/mammalian target of rapamycin (mTOR) pathway..
  99. ncbi TNFalpha mediates sepsis-induced impairment of basal and leucine-stimulated signaling via S6K1 and eIF4E in cardiac muscle
    Charles H Lang
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    J Cell Biochem 94:419-31. 2005
    ..Finally, TNFalpha, either directly or indirectly, appears to mediate the sepsis-induced defects in myocardial translation initiation...
  100. ncbi Mammalian target of rapamycin complex 1-mediated phosphorylation of eukaryotic initiation factor 4E-binding protein 1 requires multiple protein-protein interactions for substrate recognition
    Elaine A Dunlop
    Institute of Medical Genetics, Cardiff University, Heath Park, Cardiff, Wales, UK
    Cell Signal 21:1073-84. 2009
    ..Our work demonstrates the value of an in vitro mTORC1 kinase assay to characterise cell signalling components of mTORC1 involved in recognition and phosphotransfer to mTORC1 substrates...
  101. ncbi Translation of the radioresistance kinase TLK1B is induced by gamma-irradiation through activation of mTOR and phosphorylation of 4E-BP1
    Gulshan Sunavala-Dossabhoy
    Department of Biochemistry and Molecular Biology and the Feist Weiller Cancer Center, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130 3932, USA
    BMC Mol Biol 5:1. 2004
    ..We now report that radiation or doxorubicin result in an increase in the translation of TLK1B, and we have uncovered the likely mechanism for this effect...

Research Grants77

  1. Alcohol Consumption and Risk of NHL: Role of MTOR Dysfunction
    Ronald Gartenhaus; Fiscal Year: 2009
    ..Therefore, improved understanding of the underlying molecular mechanism(s) associated with the ability of EtOH to suppress mTOR activity may form the basis for the development of innovative approaches to block lymphoma growth. ..
  2. Alcohol Consumption and Risk of NHL: Role of MTOR Dysfunction
    RONALD BENJAMIN GARTENHAUS; Fiscal Year: 2010
    ..Therefore, improved understanding of the underlying molecular mechanism(s) associated with the ability of EtOH to suppress mTOR activity may form the basis for the development of innovative approaches to block lymphoma growth. ..
  3. Role of 4E-BP1 and 4E-BP2 in Translational Control
    Laura Beretta; Fiscal Year: 2006
    ..abstract_text> ..
  4. Amino Acids and Muscle Protein Synthesis
    Robert Wolfe; Fiscal Year: 2006
    ..is mediated via an mTOR-dependent signaling pathway resulting in an increased phosphorylation of the eIF4E binding protein 1 (4E-BP1) and the 70KDa ribosomal protein S6 kinase (S6K1)...
  5. Antifibrotic Drug Discovery in Acute Lung Injury
    Peter Bitterman; Fiscal Year: 2007
    ..If successful, our work will confirm or refute eIF4E as an antifibrotic therapeutic target, and may lead to the identification of new acute lung injury-specific molecular targets for antifibrotic drug discovery. ..
  6. GENES REGULATED BY C MYC
    Emmett Schmidt; Fiscal Year: 2004
    ..initiation factor eIF4E as a critical target of c-Myc because co-transfection with a dominant inhibitor of eIF4E (4EBP1) blocks transformation by c-Myc and eIF4E itself transforms cells...
  7. STRUCTURAL BASIS OF TRANSLATION INITIATION BY EIF-4E
    Gerhard Wagner; Fiscal Year: 2000
    ..We expect that this research will be relevant to the understanding of tumorigenic uncontrolled cell growth. ..
  8. INSULIN ACTION IN MUSCLE AND FAT CELL
    John Lawrence; Fiscal Year: 2000
    ..Subaims are to determine whether insulin promotes dephosphorylation of the activating site in PP1G; in rat skeletal muscle and to investigate the interactions between insulin and epinephrine on the phosphorylation of PP1G. ..
  9. Nuclear Reprogramming and Phenotype in Cloned Embryos
    Keith E Latham; Fiscal Year: 2010
    ....
  10. Nuclear Reprogramming and Phenotype in Cloned Embryos
    Keith E Latham; Fiscal Year: 2010
    ....
  11. Nuclear Reprogramming and Phenotype in Cloned Embryos
    Keith Latham; Fiscal Year: 2009
    ....
  12. Rapamycin Regulation of the Androgen Receptor: Implications in Prostate Cancer
    Paramita M Ghosh; Fiscal Year: 2010
    ..Currently, the options for patients with androgen-independent prostate cancer are limited;hence such a study would open the doors for a new treatment option. ..
  13. Rapamycin Regulation of the Androgen Receptor: Implications in Prostate Cancer
    Paramita Ghosh; Fiscal Year: 2009
    ..Currently, the options for patients with androgen-independent prostate cancer are limited; hence such a study would open the doors for a new treatment option. ..
  14. Rheb small GTPase signaling in tuberous sclerosis
    Kun Liang Guan; Fiscal Year: 2007
    ..The major cellular function of TSC2 is to decrease the phosphorylation of S6K (ribosomal S6 kinase) and 4EBP1 (eukaryotic initiation factor 4E binding protein), possibly by inhibiting mTOR (mammalian target of rapamycin)...
  15. mTOR Signaling In Chronic Myelogenous Leukemia
    TIONG ONG; Fiscal Year: 2006
    ..abstract_text> ..
  16. mTOR Signaling In Chronic Myelogenous Leukemia
    Hung Fan; Fiscal Year: 2007
    ..abstract_text> ..
  17. mTOR Signaling In Chronic Myelogenous Leukemia
    Hung Fan; Fiscal Year: 2009
    ..abstract_text> ..
  18. Multi-institutional trial: molecular analysis of margins
    Cherie Ann Nathan; Fiscal Year: 2009
    ..The activated mammalian target of rapamycin, mTOR, phosphorylates 4E-BP 1 releasing bound eIF4E to stimulate cap-dependent translation...
  19. Multi-institutional trial: molecular analysis of margins
    Cherie Ann Nathan; Fiscal Year: 2007
    ..The activated mammalian target of rapamycin, mTOR, phosphorylates 4E-BP 1 releasing bound eIF4E to stimulate cap-dependent translation...
  20. Regulation of Protein Synthesis in Neonatal Sepsis
    RENAN ORELLANA; Fiscal Year: 2007
    ..abstract_text> ..
  21. REGULATION OF PROTEIN TURNOVER IN SEPSIS
    THOMAS VARY; Fiscal Year: 2009
    ....
  22. REGULATION OF PROTEIN TURNOVER IN SEPSIS
    THOMAS VARY; Fiscal Year: 2007
    ..abstract_text> ..
  23. REGULATION OF PROTEIN TURNOVER IN SEPSIS
    THOMAS VARY; Fiscal Year: 2007
    ....
  24. Role of mTOR, a Component of the Akt Pathway, in Regulating Cardiac Function
    Gianluigi Condorelli; Fiscal Year: 2011
    ..This project will help the understanding of molecular mechanisms of anti-cancer drug-induced cardiac toxicity and finding new target molecules regulating cardiac function. ..
  25. ROLE OF PHAS-I/TOR PATHWAY AND MITOGENIC SIGNALING
    Michael McDaniel; Fiscal Year: 2002
    ..An understanding of the PHAS- I/mTOR signaling pathway to generate mitogenic mediators will provide important new insights to enhance the ability of growth factors and nutrients to stimulate Beta-cell growth. ..
  26. Signal Transduction of Type I Interferons in Malignant Cells
    Leonidas Platanias; Fiscal Year: 2009
    ....
  27. Muscle protein synthesis and gene expression in myostatin-deficient mice
    Stephen Welle; Fiscal Year: 2007
    ..of genes involved in mRNA translation, and will stimulate mRNA translation through activation of the Akt-mTOR-4EBP1/S6K1 pathway...
  28. Signal Transduction of Type I Interferons in Malignant Cells
    Leonidas C Platanias; Fiscal Year: 2010
    ....
  29. Signal Transduction of Type I Interferons in Malignant Cells
    Leonidas Platanias; Fiscal Year: 2007
    ....
  30. Autophagy and protein translation in neural function & neurodegeneration
    Albert R La Spada; Fiscal Year: 2010
    ..Hence, this project will examine whether reduced protein synthesis is truly neuroprotective, and will attempt to uncover the regulatory interrelationships between protein translation state and autophagy pathway function. ..
  31. Autophagy and protein translation in neural function & neurodegeneration
    Albert La Spada; Fiscal Year: 2009
    ..Hence, this project will examine whether reduced protein synthesis is truly neuroprotective, and will attempt to uncover the regulatory interrelationships between protein translation state and autophagy pathway function. ..
  32. REGULATION OF PROTEIN TURNOVER IN SEPSIS
    Scot R Kimball; Fiscal Year: 2010
    ....