eukaryotic initiation factor 4f

Summary

Summary: A trimeric peptide initiation factor complex that associates with the 5' MRNA CAP STRUCTURE of RNA and plays an essential role in MRNA TRANSLATION. It is composed of EUKAYROTIC INITIATION FACTOR-4A; EUKARYOTIC INITIATION FACTOR-4E; and EUKAYROTIC INITIATION FACTOR-4G.

Top Publications

  1. ncbi Activation of translation complex eIF4F is essential for the genesis and maintenance of the malignant phenotype in human mammary epithelial cells
    Svetlana Avdulov
    Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA
    Cancer Cell 5:553-63. 2004
  2. ncbi Modulation of the helicase activity of eIF4A by eIF4B, eIF4H, and eIF4F
    G W Rogers
    Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106 4935, USA
    J Biol Chem 276:30914-22. 2001
  3. ncbi Cap-dependent translation initiation in eukaryotes is regulated by a molecular mimic of eIF4G
    J Marcotrigiano
    Laboratories of Molecular Biophysics, Rockefeller University, New York, New York 10021, USA
    Mol Cell 3:707-16. 1999
  4. pmc Intrinsic RNA binding by the eukaryotic initiation factor 4F depends on a minimal RNA length but not on the m7G cap
    Nicholas M Kaye
    Department of Biochemistry, Center for RNA Molecular Biology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA
    J Biol Chem 284:17742-50. 2009
  5. pmc Selective modification of eukaryotic initiation factor 4F (eIF4F) at the onset of cell differentiation: recruitment of eIF4GII and long-lasting phosphorylation of eIF4E
    Sandrine Caron
    Department of Hematology, Institut Cochin, INSERM U567, Maternite Port Royal, 123 Bd Port Royal, 75014 Paris, France
    Mol Cell Biol 24:4920-8. 2004
  6. pmc The translation initiation factor eIF-4E binds to a common motif shared by the translation factor eIF-4 gamma and the translational repressors 4E-binding proteins
    S Mader
    Department of Biochemistry, McGill University, Montreal, Quebec, Canada
    Mol Cell Biol 15:4990-7. 1995
  7. pmc Translation initiation factor eIF4G mediates in vitro poly(A) tail-dependent translation
    S Z Tarun
    Department of Molecular and Cell Biology, 401 Barker Hall, University of California, Berkeley, Berkeley, CA 94720, USA
    Proc Natl Acad Sci U S A 94:9046-51. 1997
  8. ncbi Insulin and IGF-I stimulate the formation of the eukaryotic initiation factor 4F complex and protein synthesis in C2C12 myotubes independent of availability of external amino acids
    Wei Hua Shen
    Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA
    J Endocrinol 185:275-89. 2005
  9. pmc A novel functional human eukaryotic translation initiation factor 4G
    A Gradi
    Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, Quebec, Canada
    Mol Cell Biol 18:334-42. 1998
  10. ncbi eIF4 initiation factors: effectors of mRNA recruitment to ribosomes and regulators of translation
    A C Gingras
    Department of Biochemistry McGill University, Montreal, Quebec, Canada
    Annu Rev Biochem 68:913-63. 1999

Detail Information

Publications214 found, 100 shown here

  1. ncbi Activation of translation complex eIF4F is essential for the genesis and maintenance of the malignant phenotype in human mammary epithelial cells
    Svetlana Avdulov
    Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA
    Cancer Cell 5:553-63. 2004
    ..Thus, eIF4F activation is an essential component of the malignant phenotype in breast carcinoma...
  2. ncbi Modulation of the helicase activity of eIF4A by eIF4B, eIF4H, and eIF4F
    G W Rogers
    Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106 4935, USA
    J Biol Chem 276:30914-22. 2001
    ..A simple model of how eIF4B or eIF4H affects the duplex unwinding mechanism of eIF4A is proposed...
  3. ncbi Cap-dependent translation initiation in eukaryotes is regulated by a molecular mimic of eIF4G
    J Marcotrigiano
    Laboratories of Molecular Biophysics, Rockefeller University, New York, New York 10021, USA
    Mol Cell 3:707-16. 1999
    ..The implications of our results for translation initiation are discussed in detail, and a molecular mechanism for relief of translation inhibition following phosphorylation of the 4E-BPs is proposed...
  4. pmc Intrinsic RNA binding by the eukaryotic initiation factor 4F depends on a minimal RNA length but not on the m7G cap
    Nicholas M Kaye
    Department of Biochemistry, Center for RNA Molecular Biology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA
    J Biol Chem 284:17742-50. 2009
    The eukaryotic initiation factor 4F (eIF4F) is thought to be the first factor to bind mRNA during 7-methylguanosine (m7G) cap-dependent translation initiation...
  5. pmc Selective modification of eukaryotic initiation factor 4F (eIF4F) at the onset of cell differentiation: recruitment of eIF4GII and long-lasting phosphorylation of eIF4E
    Sandrine Caron
    Department of Hematology, Institut Cochin, INSERM U567, Maternite Port Royal, 123 Bd Port Royal, 75014 Paris, France
    Mol Cell Biol 24:4920-8. 2004
    ..Our data further indicate that cytokines such as thrombopoietin can differentially regulate eIF4GI/II activities. These results provide the first evidence that eIF4GI/II does fulfill selective roles in mammalian cells...
  6. pmc The translation initiation factor eIF-4E binds to a common motif shared by the translation factor eIF-4 gamma and the translational repressors 4E-binding proteins
    S Mader
    Department of Biochemistry, McGill University, Montreal, Quebec, Canada
    Mol Cell Biol 15:4990-7. 1995
    ..These results shed light on the mechanisms of eIF-4F assembly and on the translational regulation by insulin and growth factors...
  7. pmc Translation initiation factor eIF4G mediates in vitro poly(A) tail-dependent translation
    S Z Tarun
    Department of Molecular and Cell Biology, 401 Barker Hall, University of California, Berkeley, Berkeley, CA 94720, USA
    Proc Natl Acad Sci U S A 94:9046-51. 1997
    ..These data suggest that eIF4G mediates poly(A) tail stimulated translation in vitro, and that Pab1p and the domain encompassing the Pab1p-binding site on eIF4G can compensate for partial loss of eIF4E function in vivo...
  8. ncbi Insulin and IGF-I stimulate the formation of the eukaryotic initiation factor 4F complex and protein synthesis in C2C12 myotubes independent of availability of external amino acids
    Wei Hua Shen
    Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA
    J Endocrinol 185:275-89. 2005
    ..We conclude that in C2C12 myotubes, insulin and IGF-I may regulate protein synthesis and translation initiation independent of external amino acid supply via the phosphatidylinositol-3 kinase-PKB/Akt-mTOR pathway...
  9. pmc A novel functional human eukaryotic translation initiation factor 4G
    A Gradi
    Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, Quebec, Canada
    Mol Cell Biol 18:334-42. 1998
    ..These results may have important implications for the understanding of the mechanism of shutoff of host protein synthesis following picornavirus infection...
  10. ncbi eIF4 initiation factors: effectors of mRNA recruitment to ribosomes and regulators of translation
    A C Gingras
    Department of Biochemistry McGill University, Montreal, Quebec, Canada
    Annu Rev Biochem 68:913-63. 1999
    ..The recent determination of the structure of eIF4E at atomic resolution has provided insight about how translation is initiated and regulated. Evidence suggests that eIF4F is also implicated in malignancy and apoptosis...
  11. pmc Eukaryotic translation initiation factor 4GI and p97 promote cellular internal ribosome entry sequence-driven translation
    Patrick Hundsdoerfer
    Gene Expression Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, D 69117 Heidelberg, Germany
    Proc Natl Acad Sci U S A 102:13421-6. 2005
    ....
  12. pmc TIF4631 and TIF4632: two yeast genes encoding the high-molecular-weight subunits of the cap-binding protein complex (eukaryotic initiation factor 4F) contain an RNA recognition motif-like sequence and carry out an essential function
    C Goyer
    Department of Biochemistry, McGill University, Montreal, Quøebec, Canada
    Mol Cell Biol 13:4860-74. 1993
    ..Sequence comparison of TIF4631, TIF4632, and the human eIF-4F p220 subunit revealed significant stretches of homology. We have thus cloned two yeast homologs of mammalian p220...
  13. 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...
  14. 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...
  15. 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...
  16. ncbi Translation initiation in Leishmania major: characterisation of multiple eIF4F subunit homologues
    Rafael Dhalia
    Departamento de Biologia Celular, Universidade de Brasilia, Brasília 70910 900, D F, Brazil
    Mol Biochem Parasitol 140:23-41. 2005
    ..Therefore for each factor, one of the L. major forms seems to fulfil, in part at least, the expected characteristics of a translational initiation factor...
  17. ncbi Distinct signalling pathways mediate insulin and phorbol ester-stimulated eukaryotic initiation factor 4F assembly and protein synthesis in HEK 293 cells
    T P Herbert
    Department of Anatomy, The Medical Sciences Institute, University of Dundee, Dow Street, Dundee DD1 5EH, United Kingdom
    J Biol Chem 275:11249-56. 2000
    ..This report also provides evidence that increased eIF4E phosphorylation alone does not affect the assembly of the eIF4F complex or general protein synthesis...
  18. ncbi Calcineurin is required for translational control of protein synthesis in rat pancreatic acini
    Maria Dolors Sans
    Department of Molecular and Integrative Physiology, University of Michigan Medical School, 1301 E Catherine St, 7737 Med Sci II, Ann Arbor, MI 48109 0622, USA
    Am J Physiol Cell Physiol 287:C310-9. 2004
    ..From these results, we conclude that calcineurin activity is required for protein synthesis, and this action may be related to an effect on the formation of the mRNA cap binding complex and the elongation processes...
  19. ncbi Reinitiation and recycling are distinct processes occurring downstream of translation termination in yeast
    Lukas Rajkowitsch
    Posttranscriptional Control Group, Department of Biomolecular Sciences, UMIST, P O Box 88, M60 1QD, Manchester, UK
    J Mol Biol 335:71-85. 2004
    ....
  20. ncbi Steroid and oxygen effects on eIF4F complex, mTOR, and ENaC translation in fetal lung epithelia
    Gail Otulakowski
    CIHR Group in Lung Development, Program in Physiology and Experimental Medicine, Hospital for Sick Children Research Institute, Toronto, ON, Canada
    Am J Respir Cell Mol Biol 37:457-66. 2007
    ..We speculate that at birth increased Po(2) acts with GC through an mTOR-related pathway to increase alpha-ENaC protein synthesis, thereby promoting lung fluid absorption...
  21. ncbi Viral stress-inducible protein p56 inhibits translation by blocking the interaction of eIF3 with the ternary complex eIF2.GTP.Met-tRNAi
    Daniel J Hui
    Department of Molecular Biology, The Lerner Research Institute, Cleveland Clinic Foundation, and Graduate Program in Molecular Virology, Case Western Reserve University School of Medicine, Ohio, USA
    J Biol Chem 278:39477-82. 2003
    ..Whereas cap-dependent initiation was severely inhibited by p56, internal ribosomal entry site-mediated translation appeared to be insensitive to p56...
  22. ncbi [Minor secondary-structure variation in the 5'-untranslated region of the beta-globin mRNA changes the concentration requirements for eIF2]
    S E Dmitriev
    Belozersky Institute of Physico Chemical Biology, Moscow State University, Moscow, 119899 Russia
    Mol Biol (Mosk) 37:494-503. 2003
    ..According to a model proposed, eIF2 not only delivers Met-tRNA, but it also stabilizes the complex of the 40S ribosome subunit with 5'-UTR, which is of particular importance for translation initiation on templates with structured 5'-UTR...
  23. ncbi Caerulein-induced acute pancreatitis inhibits protein synthesis through effects on eIF2B and eIF4F
    Maria Dolors Sans
    Department of Molecular and Integrative Physiology, The University of Michigan Medical School, Ann Arbor, MI 48109 0622, USA
    Am J Physiol Gastrointest Liver Physiol 285:G517-28. 2003
    ....
  24. pmc Impaired binding of standard initiation factors mediates poliovirus translation attenuation
    Kerstin Ochs
    Institute of Biochemistry, Faculty of Medicine, Justus Liebig Universitat Giessen, Germany
    J Virol 77:115-22. 2003
    ....
  25. pmc The histone 3'-terminal stem-loop-binding protein enhances translation through a functional and physical interaction with eukaryotic initiation factor 4G (eIF4G) and eIF3
    Jun Ling
    Department of Biochemistry, University of California, Riverside, California 92521 0129, USA
    Mol Cell Biol 22:7853-67. 2002
    ..These data indicate that SLBP stimulates the translation of histone mRNAs through a functional interaction with both the mRNA stem-loop and the 5' cap that is mediated by eIF4G and eIF3...
  26. ncbi SF2/ASF TORCs up translation
    Martin Bushell
    School of Pharmacy, Centre for Biomolecular Sciences, University of Nottingham, University Park, NG7 2RD Nottingham, UK
    Mol Cell 30:262-3. 2008
    ..In a recent issue of Molecular Cell, Michlewski et al. (2008) show that SF2/ASF, a splicing factor, stimulates translation initiation by directly recruiting the mammalian target of rapamycin (mTOR) to a subset of mRNAs...
  27. ncbi Homogenous time resolved fluorescence assay to identify modulators of cap-dependent translation initiation
    Regina Cencic
    Department of Biochemistry, McIntyre Medical Sciences Building, 3655 Promenade Sir William Osler, McGill University, Montreal, Quebec, Canada, H3G 1Y6
    Comb Chem High Throughput Screen 10:181-8. 2007
    ..We have performed a small molecule chemical screen of >73,000 compounds using this assay...
  28. 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...
  29. ncbi Modulation of eukaryotic mRNA stability via the cap-binding translation complex eIF4F
    Carmen Velasco Ramirez
    Posttranscriptional Control Group, Department of Biomolecular Sciences, University of Manchester Institute of Science and Technology UMIST, P O Box 88, M60 1QD, UK
    J Mol Biol 318:951-62. 2002
    ..Thus, the accessibility of the cap to Dcp1 in vivo is not simply controlled by competition with eIF4E, but is subject to switching between molecular states with different levels of access...
  30. ncbi Regulation of global and specific mRNA translation by amino acids
    Scot R Kimball
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    J Nutr 132:883-6. 2002
    ..Thus, deprivation of essential amino acids not only directly and rapidly represses global mRNA translation, but also potentially results in a reduction in the capacity to synthesize protein...
  31. pmc 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...
  32. ncbi Was the initiation of translation in early eukaryotes IRES-driven?
    Greco Hernández
    Institut für Biochemie und Molekulare Medizin, Universitat Bern, Buhlstrasse 28, 3012 Bern, Switzerland
    Trends Biochem Sci 33:58-64. 2008
    ..Thus, the contemporary cellular IRESs might be relics of the past...
  33. ncbi Feeding activates protein synthesis in mouse pancreas at the translational level without increase in mRNA
    Maria Dolors Sans
    Department of Molecular and Integrative Physiology, The University of Michigan Medical School, Ann Arbor, Michigan 48109 0622, USA
    Am J Physiol Gastrointest Liver Physiol 287:G667-75. 2004
    ..By contrast, feeding did not affect eIF2B activity. Thus food intake stimulates pancreatic protein synthesis and translational effectors without increasing digestive enzyme mRNA levels...
  34. ncbi Skeletal muscle protein synthesis and degradation exhibit sexual dimorphism after chronic alcohol consumption but not acute intoxication
    Charles H Lang
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, PA 17033, USA
    Am J Physiol Endocrinol Metab 292:E1497-506. 2007
    ....
  35. pmc Eukaryotic translation initiation factor 4E availability controls the switch between cap-dependent and internal ribosomal entry site-mediated translation
    Yuri V Svitkin
    Department of Biochemistry, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec, Canada H3G 1Y6
    Mol Cell Biol 25:10556-65. 2005
    ..These data explain numerous reported observations where viral mRNAs are preferentially translated during infection...
  36. ncbi Structural roles for human translation factor eIF3 in initiation of protein synthesis
    Bunpote Siridechadilok
    Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA
    Science 310:1513-5. 2005
    ..Detailed modeling of eIF3 and eIF4F onto the 40S ribosomal subunit reveals that eIF3 uses eIF4F or the HCV IRES in structurally similar ways to position the mRNA strand near the exit site of 40S, promoting initiation complex assembly...
  37. pmc Gene expression during acute and prolonged hypoxia is regulated by distinct mechanisms of translational control
    Marianne Koritzinsky
    Department of Radiation Oncology MAASTRO, GROW Research Institute, University of Maastricht, The Netherlands
    EMBO J 25:1114-25. 2006
    ..Together, our data indicate that acute and prolonged hypoxia regulates mRNA translation through distinct mechanisms, each with important contributions to hypoxic gene expression...
  38. pmc Calicivirus translation initiation requires an interaction between VPg and eIF 4 E
    Ian Goodfellow
    School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading RG6 6AJ, UK
    EMBO Rep 6:968-72. 2005
    ..This work lends support to the idea that calicivirus VPg acts as a novel 'cap substitute' during initiation of translation on virus mRNA...
  39. 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...
  40. pmc The 3' cap-independent translation element of Barley yellow dwarf virus binds eIF4F via the eIF4G subunit to initiate translation
    Krzysztof Treder
    Plant Pathology Department, Iowa State University, Ames, Iowa 50011, USA
    RNA 14:134-47. 2008
    ..These results and previous observations are consistent with a model in which eIF4F is delivered to the 5' UTR by the BTE, and they show that eIF4G, but not eIF4E, plays a major role in this novel mechanism of cap-independent translation...
  41. ncbi Hypoxia and regulation of messenger RNA translation
    Marianne Koritzinsky
    Department of Radiation Oncology Maastro Lab, GROW Research Institute, Maastricht University, Maastricht, The Netherlands
    Methods Enzymol 435:247-73. 2007
    ..We have emphasized the qualitative and quantitative analysis of polysome profiles, which can yield interesting information regarding the mechanistic basis for (gene-specific) translational regulation...
  42. ncbi "Translating" tumor hypoxia: unfolded protein response (UPR)-dependent and UPR-independent pathways
    Constantinos Koumenis
    Department of Radiation Oncology, Maastricht Radiation Oncology Maastro Laboratory, GROW Research Institute, USN50 23 University of Maastricht, The Netherlands
    Mol Cancer Res 4:423-36. 2006
    ..during hypoxia is also inhibited through the inactivation of a second eukaryotic initiation complex, eukaryotic initiation factor 4F. At least part of this inhibition is mediated through a Redd1 and tuberous sclerosis complex 1/2-..
  43. ncbi Interaction of genome-linked protein (VPg) of turnip mosaic virus with wheat germ translation initiation factors eIFiso4E and eIFiso4F
    Mateen A Khan
    Department of Chemistry, Hunter College and the Graduate Center of the City University of New York, New York, New York 10021, USA
    J Biol Chem 281:28002-10. 2006
    ..Furthermore, the formation of a protein-RNA complex containing VPg suggests the possibility of direct participation of VPg in the translation of the viral genome...
  44. ncbi Glucose-stimulated protein synthesis in pancreatic beta-cells parallels an increase in the availability of the translational ternary complex (eIF2-GTP.Met-tRNAi) and the dephosphorylation of eIF2 alpha
    Edith Gomez
    Department of Cell Physiology and Pharmacology, University of Leicester, Maurice Shock Medical Sciences Building, University Road, Leicester LE1 9HN, UK
    J Biol Chem 279:53937-46. 2004
    ....
  45. ncbi S6K1- and betaTRCP-mediated degradation of PDCD4 promotes protein translation and cell growth
    N Valerio Dorrello
    Department of Pathology, NYU Cancer Institute, New York University School of Medicine, 550 First Avenue, MSB 599, New York, NY 10016, USA
    Science 314:467-71. 2006
    ..We propose that regulated degradation of PDCD4 in response to mitogens allows efficient protein synthesis and consequently cell growth...
  46. ncbi The proteasome inhibitor, MG132, promotes the reprogramming of translation in C2C12 myoblasts and facilitates the association of hsp25 with the eIF4F complex
    Joanne L Cowan
    Department of Biochemistry, School of Life Sciences, University of Sussex, Falmer, Brighton, UK
    Eur J Biochem 271:3596-611. 2004
    ....
  47. 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...
  48. ncbi Suppression of translation during in vitro maturation of pig oocytes despite enhanced formation of cap-binding protein complex eIF4F and 4E-BP1 hyperphosphorylation
    Zdenka Ellederova
    Institute of Animal Physiology and Genetics, Academy of Sciences of the Czech Republic, Libechov, Czech Republic
    Mol Reprod Dev 73:68-76. 2006
    ....
  49. pmc 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...
  50. ncbi Vector design for optimal protein expression
    A W van der Velden
    Utrecht University, The Netherlands
    Biotechniques 31:572, 574, 576-80, passim. 2001
    ..These aspects result in high-level expression of exactly the desired protein. Easily obtainable examples of the sequences [5'UTR, 3'UTR, and poly(A) signal] are suggested...
  51. pmc Suppression of cap-dependent translation in mitosis
    S Pyronnet
    Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, Quebec H3G 1Y6, Canada
    Genes Dev 15:2083-93. 2001
    ..Thus, inhibition of cap-dependent translation in mitosis results from a combination of phosphorylation modifications leading to eIF4F complex disruption...
  52. ncbi Changes in integrity and association of eukaryotic protein synthesis initiation factors during apoptosis
    M Bushell
    Biochemistry Group, School of Biological Sciences, University of Sussex, Brighton, UK
    Eur J Biochem 267:1083-91. 2000
    ..These events are likely to contribute to the inhibition of protein synthesis seen under these conditions...
  53. ncbi Interaction of polyadenylate-binding protein with the eIF4G homologue PAIP enhances translation
    A W Craig
    Department of Biochemistry, McGill University, Montreal, Quebec, Canada
    Nature 392:520-3. 1998
    ..Overexpression of PAIP-1 in COS-7 cells stimulates translation, perhaps by providing a physical link between the mRNA termini...
  54. pmc Phosphorylation of the cap-binding protein eukaryotic translation initiation factor 4E by protein kinase Mnk1 in vivo
    A J Waskiewicz
    Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
    Mol Cell Biol 19:1871-80. 1999
    ..This suggests that phosphorylation of eIF4E is catalyzed by Mnk1 or a very similar kinase in cells and is independent of other mitogenic signals that release eIF4E from 4EBP1...
  55. pmc Modifications of eukaryotic initiation factor 4F (eIF4F) in adult cardiocytes by adenoviral gene transfer: differential effects on eIF4F activity and total protein synthesis rates
    A N Saghir
    Department of Medicine, Strom Thurmond Biomedical ResearchBuilding, Room 303, 114 Doughty Street, Charleston, SC 29403, USA
    Biochem J 356:557-66. 2001
    In adult feline cardiocytes, increases in eukaryotic initiation factor 4F (eIF4F) activity are correlated with accelerated rates of total protein synthesis produced in response to increased load...
  56. pmc Chaperone hsp27 inhibits translation during heat shock by binding eIF4G and facilitating dissociation of cap-initiation complexes
    R Cuesta
    Department of Microbiology, New York University School of Medicine and Kaplan Cancer Center, New York, New York 10016 USA
    Genes Dev 14:1460-70. 2000
    ..These results therefore demonstrate that Hsp27 is a heat-induced inhibitor of eIF4F-dependent mRNA translation...
  57. ncbi Evidence that eukaryotic initiation factor (eIF) 2 is a cap-binding protein that stimulates cap recognition by eIF-4B and eIF-4F
    H A Van Heugten
    Department of Molecular Cell Biology, University of Utrecht, The Netherlands
    J Biol Chem 266:7279-84. 1991
    ..These observations indicate a role for eIF-2 in the mRNA recognition...
  58. ncbi New initiation factor activity required for globin mRNA translation
    J A Grifo
    J Biol Chem 258:5804-10. 1983
    ..Unlike eIF-4F, cap binding protein of Mr approximately 24,000 isolated by affinity chromatography on m7GDP-Sepharose does not stimulate globin synthesis in the reconstituted system...
  59. ncbi Characterization of wild-type and Ser53 mutant eukaryotic initiation factor 4E overexpression in mammalian cells
    R J Kaufman
    Genetics Institute, Cambridge, Massachusetts 02140
    J Biol Chem 268:11902-9. 1993
    ..These results demonstrate that phosphorylation of eIF-4E at residue 53 is not required for interaction with p220 and suggest that Ser53 phosphorylation may not be required for cap-dependent translation initiation in this system...
  60. pmc 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
    ....
  61. pmc 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...
  62. pmc A new translational regulator with homology to eukaryotic translation initiation factor 4G
    H Imataka
    Department of Biochemistry and McGill Cancer Centre, McGill University, Montreal, Quebec, Canada
    EMBO J 16:817-25. 1997
    ..These results suggest that p97 functions as a general repressor of translation by forming translationally inactive complexes that include eIF4A and eIF3, but exclude eIF4E...
  63. pmc Tombusvirus recruitment of host translational machinery via the 3' UTR
    Beth L Nicholson
    Department of Biology, York University, Toronto, Ontario M3J 1P3, Canada
    RNA 16:1402-19. 2010
    ..Moreover, the virus-host interplay defined in this study provides insights into natural host resistance mechanisms that have been linked to 3'CITE activity...
  64. pmc Factor requirements for translation initiation on the Simian picornavirus internal ribosomal entry site
    Sylvain de Breyne
    Department of Microbiology and Immunology, State University of New York Downstate Medical Center, Brooklyn, New York 11203, USA
    RNA 14:367-80. 2008
    ..Although these 40S/IRES/tRNA complexes could not form active 80S ribosomes, this constitutes a second difference between the SPV9 and HP IRESs. eIF1 destabilized the eIF2-independent ribosomal binding of initiator tRNA...
  65. pmc Protein phosphatase 2A negatively regulates eukaryotic initiation factor 4E phosphorylation and eIF4F assembly through direct dephosphorylation of Mnk and eIF4E
    Yikun Li
    Department of Hematology and Medical Oncology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, GA 30322, USA
    Neoplasia 12:848-55. 2010
    ....
  66. pmc The eukaryotic initiation factor (eIF) 4G HEAT domain promotes translation re-initiation in yeast both dependent on and independent of eIF4A mRNA helicase
    Ryosuke Watanabe
    Molecular, Cellular, and Developmental Biology Program, Division of Biology, Kansas State University, Manhattan, Kansas 66506, USA
    J Biol Chem 285:21922-33. 2010
    ..Based on the RNA-binding activities identified within the unstructured segments flanking the eIF4G2 HEAT domain, we discuss the role of the HEAT domain in scanning beyond loading eIF4A onto the pre-initiation complex...
  67. pmc Acute and chronic ethanol consumption differentially impact pathways limiting hepatic protein synthesis
    Anne M Karinch
    Department of Cellular and Molecular Physiology, MC H166, Penn State Univ College of Medicine, 500 Univ Drive, Hershey, PA 17033, USA
    Am J Physiol Endocrinol Metab 295:E3-9. 2008
    ..Enhanced phosphorylation of eIF2alpha represents a unique response of liver to alcohol intoxication, because the ethanol-induced elevation of eIF2alpha(P) is not observed in skeletal muscle or heart...
  68. pmc Repair of isoaspartate formation modulates the interaction of deamidated 4E-BP2 with mTORC1 in brain
    Michael Bidinosti
    Department of Biochemistry and Goodman Cancer Centre, McGill University, Montreal, Quebec H3G 1Y6, Canada
    J Biol Chem 285:19402-8. 2010
    ..step of translation initiation is recognition of the mRNA 5' m(7)GpppN cap structure by the eukaryotic initiation factor 4F (eIF4F), a heterotrimeric complex consisting of the cap-binding protein, eIF4E, along with eIF4G, and ..
  69. pmc Leaky scanning is the predominant mechanism for translation of human papillomavirus type 16 E7 oncoprotein from E6/E7 bicistronic mRNA
    S N Stacey
    Cancer Research Campaign, Department of Molecular Biology, Paterson Institute for Cancer Research, Christie Hospital, Manchester M20 4BX, United Kingdom
    J Virol 74:7284-97. 2000
    ..These findings suggest that the E6 region of HPV-16 comprises features that sponsor both translation of the E6 protein and enhancement of translation at a downstream site...
  70. ncbi Intact eukaryotic initiation factor 4G is required for hepatitis A virus internal initiation of translation
    A M Borman
    CNRS URA 1966, Institut Pasteur, Paris, France
    Virology 237:129-36. 1997
    ..Thus the HAV IRES requires intact eIF4G for activity. This is unique among the picornavirus IRESes studied to date and may help explain why HAV does not inhibit host cell translation during viral infection...
  71. pmc Human eukaryotic translation initiation factor 4G (eIF4G) possesses two separate and independent binding sites for eIF4A
    H Imataka
    Department of Biochemistry and McGill Cancer Centre, McGill University, Montreal, Quebec, Canada
    Mol Cell Biol 17:6940-7. 1997
    ..In contrast to eIF4G, human p97, a translation inhibitor with homology to eIF4G, binds eIF4A only through the amino-terminal proximal region, which is homologous to the middle domain of eIF4G...
  72. 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
    ....
  73. pmc Control of eIF4E cellular localization by eIF4E-binding proteins, 4E-BPs
    Liwei Rong
    Department of Biochemistry, McGill University, Montreal, Quebec H3G 1Y6, Canada
    RNA 14:1318-27. 2008
    ..A dramatic loss of nuclear 4E-BP1 occurs in c-Ha-Ras-expressing MEFs, which fail to show starvation-induced nuclear accumulation of eIF4E. Therefore, 4E-BP1 is a regulator of eIF4E cellular localization...
  74. ncbi Involvement of stress-activated protein kinase and p38/RK mitogen-activated protein kinase signaling pathways in the enhanced phosphorylation of initiation factor 4E in NIH 3T3 cells
    S J Morley
    Biochemistry Laboratory, School of Biological Sciences, University of Sussex, Falmer, Brighton BN1 9QG, United Kingdom
    J Biol Chem 272:17887-93. 1997
    ....
  75. ncbi A single amino acid change in protein synthesis initiation factor 4G renders cap-dependent translation resistant to picornaviral 2A proteases
    B J Lamphear
    Department of Biochemistry and Molecular Biology, Louisiana State University Medical Center, Shreveport 71130 3932, USA
    Biochemistry 35:15726-33. 1996
    ..These results support the model that 2A proteases inhibit cap-dependent translation through direct proteolysis of eIF4G...
  76. ncbi Adenovirus infection inactivates the translational inhibitors 4E-BP1 and 4E-BP2
    A C Gingras
    Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, Quebec, H3G 1Y6, Canada
    Virology 237:182-6. 1997
    ..Findings similar to those described here were reported for 4E-BP1 by D. Feigenblum and R. J. Schneider (1996, Mol. Cell. Biol. 16, 5450-5457)...
  77. pmc 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...
  78. ncbi Chronic alcohol feeding impairs hepatic translation initiation by modulating eIF2 and eIF4E
    C H Lang
    Department of Cellular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    Am J Physiol 277:E805-14. 1999
    ..In summary, these data suggest that chronic alcohol consumption impairs translation initiation in liver by altering eIF2B activity as well as eIF4F function via changes in eIF4E availability...
  79. pmc Sumoylation of eIF4E activates mRNA translation
    Xiang Xu
    Department of Pharmacology and Chemical Biology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, 5117 Centre Avenue, Suite 2 42D, Pittsburgh, Pennsylvania 15213, USA
    EMBO Rep 11:299-304. 2010
    ..These data indicate that sumoylation is a new fundamental regulatory mechanism of protein synthesis. Our findings suggest further that eIF4E sumoylation might be important in promoting human cancers...
  80. pmc 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...
  81. pmc Interaction of eukaryotic translation initiation factor 4G with the nuclear cap-binding complex provides a link between nuclear and cytoplasmic functions of the m(7) guanosine cap
    L McKendrick
    Department of Biochemistry, School of Biological Sciences, University of Sussex, Falmer, Brighton BN1 9QG, United Kingdom
    Mol Cell Biol 21:3632-41. 2001
    ..This may provide a mechanism to couple nuclear and cytoplasmic functions of the mRNA cap structure...
  82. pmc Uncoupling stress granule assembly and translation initiation inhibition
    Sophie Mokas
    Département de Biologie médicale, Centre Hospitalier Universitaire de Québec Centre De Recherche Hôpital Saint François D assise, Universite Laval, Quebec, QC, Canada
    Mol Biol Cell 20:2673-83. 2009
    ..Our study identifies translation initiation steps and factors involved in SG formation as well as those that can be targeted without induction of SGs...
  83. pmc A region rich in aspartic acid, arginine, tyrosine, and glycine (DRYG) mediates eukaryotic initiation factor 4B (eIF4B) self-association and interaction with eIF3
    N Methot
    Department of Biochemistry, McGill University, Montreal, Quebec, Canada
    Mol Cell Biol 16:5328-34. 1996
    The binding of mRNA to the ribosome is mediated by eukaryotic initiation factors eukaryotic initiation factor 4F (eIF4F), eIF4B, eIF4A, and eIF3, eIF4F binds to the mRNA cap structure and, in combination with eIF4B, is believed to unwind ..
  84. ncbi AICAR treatment for 14 days normalizes obesity-induced dysregulation of TORC1 signaling and translational capacity in fasted skeletal muscle
    Joshua C Drake
    Division of Exercise Physiology, West Virginia University School of Medicine, Morgantown, West Virginia, USA
    Am J Physiol Regul Integr Comp Physiol 299:R1546-54. 2010
    ..by sucrose density gradient fractionation of ribosomes, total and ribosome-associated RNA content, eukaryotic initiation factor 4F complex formation, and eukaryotic initiation factor 4G phosphorylation...
  85. 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 cap is recognized by eukaryotic initiation factor 4F (eIF4F), which consists of three polypeptides, including eIF4E, the cap-binding protein subunit...
  86. 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
    ..These data highlight the importance of modulating 4E-BP1 function, and eIF4F complex levels, in the direct antitumor effect of enzastaurin and suggest that 4E-BP1 function may serve as a promising determinant of enzastaurin activity...
  87. 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
    ....
  88. pmc High affinity RNA for mammalian initiation factor 4E interferes with mRNA-cap binding and inhibits translation
    Kiyotaka Mochizuki
    Department of Basic Medical Sciences, Institute of Medical Science, University of Tokyo, 4 6 1 Shirokanedai, Minato ku, Tokyo 108 8639, Japan
    RNA 11:77-89. 2005
    ..The genetic mutation and affinity study of variant eIF4E proteins suggests that aptamer 1 binds to eIF4E adjacent to the entrance of the cap-binding slot and blocks the cap-binding pocket, thereby inhibiting translation initiation...
  89. ncbi Eukaryotic translation initiation factor 4E induced progression of primary human mammary epithelial cells along the cancer pathway is associated with targeted translational deregulation of oncogenic drivers and inhibitors
    Ola Larsson
    Department of Medicine, University of Minnesota, 420 Delaware Street, Minneapolis, MN 55455, USA
    Cancer Res 67:6814-24. 2007
    ....
  90. pmc Cap-dependent eukaryotic initiation factor-mRNA interactions probed by cross-linking
    Lisa Lindqvist
    Department of Biochemistry, Faculty of Medicine, McGill University, Montreal, Quebec H3G 1Y6, Canada
    RNA 14:960-9. 2008
    ..Using this approach, we demonstrate interactions between eIF4G, eIF4H, and eIF3 subunits with the mRNA during the cap recognition process...
  91. ncbi Analysis of mRNA associated factors during bovine oocyte maturation and early embryonic development
    Corinna Siemer
    Research Institute for the Biology of Farm Animals FBN Dummerstorf, 18196 Dummerstorf, Germany
    Mol Reprod Dev 76:1208-19. 2009
    ..Therefore, it is likely that in general the reduction in PABP1 and 3 abundance represses overall translation during early embryonic development...
  92. ncbi Natural occurrence and physiological role of a truncated eIF4E in the porcine endometrium during implantation
    Karin Wollenhaupt
    Department of Reproductive Biology, Leibniz Institute for Farm Animal Biology, Wilhelm Stahl Allee 2, D 18196 Dummerstorf, Germany
    Biochem J 432:353-63. 2010
    ..Together with the impaired eIF4G-PABP interaction, the modified translational initiation might particularly regulate protein synthesis during conceptus attachment at the time of implantation...
  93. ncbi Nuclear assortment of eIF4E coincides with shut-off of host protein synthesis upon poliovirus infection
    R Sukarieh
    Department of Biochemistry, McGill University, Montreal, Quebec, Canada
    J Gen Virol 91:1224-8. 2010
    ..We postulate that eIF4E nuclear relocalization may contribute to the shut-off of host protein synthesis that is a hallmark of poliovirus infection by perturbing the circular status of actively translating mRNAs...
  94. pmc 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
    ....
  95. pmc Poly(A)-binding protein is differentially required for translation mediated by viral internal ribosome entry sites
    Shelton S Bradrick
    Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
    RNA 13:1582-93. 2007
    ..Collectively, the observed differential effects of PABP and poly(A) on translation imply mechanistic differences between viral IRES elements and suggest modulating roles for PABP and the poly(A) tail at multiple phases of translation...
  96. ncbi Differential contribution of the MTOR and MNK pathways to the regulation of mRNA translation in meiotic and postmeiotic mouse male germ cells
    Valeria Messina
    Section of Anatomy, Department of Public Health and Cell Biology, University of Rome Tor Vergata, Rome, Italy
    Biol Reprod 83:607-15. 2010
    ....
  97. pmc Translation initiation factor 4B homodimerization, RNA binding, and interaction with Poly(A)-binding protein are enhanced by zinc
    Shijun Cheng
    Department of Biochemistry, University of California, Riverside, California 92521 0129, USA
    J Biol Chem 283:36140-53. 2008
    ..Our observations suggest that wheat eIF4B can dimerize but requires zinc. Moreover zinc controls the partner protein selection of PABP such that the interaction with eIF4B is preferred over eIFiso4G...
  98. pmc Eukaryotic initiation factor 6 is rate-limiting in translation, growth and transformation
    Valentina Gandin
    Molecular Histology and Cell Growth Laboratory, San Raffaele Science Institute, Via Olgettina 58, 20132 Milan, Italy
    Nature 455:684-8. 2008
    ..Furthermore, eIF6(+/-) cells are resistant to oncogene-induced transformation. Thus, eIF6 is the first eIF associated with the large 60S subunit that regulates translation in response to extracellular signals...
  99. ncbi Distinct induction patterns and functions of two closely related interferon-inducible human genes, ISG54 and ISG56
    Fulvia Terenzi
    Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA
    J Biol Chem 281:34064-71. 2006
    ..Thus, although similar in structure, the human P54 and P56 proteins are induced differently and function differently...
  100. pmc Translation of non-capped mRNAs in a eukaryotic cell-free system: acceleration of initiation rate in the course of polysome formation
    Olga M Alekhina
    Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow Region, Russia
    Nucleic Acids Res 35:6547-59. 2007
    ..The eIF4F-mediated circularization of polysomes may be considered as a possible event that leads to the re-initiation switch and the resultant acceleration effect...
  101. pmc Differential inhibition of protein translation machinery by curcumin in normal, immortalized, and malignant oral epithelial cells
    Nitin Chakravarti
    Department of Thoracic Head and Neck Medical Oncology, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Cancer Prev Res (Phila) 3:331-8. 2010
    ....

Research Grants45

  1. Translational Control in IPF
    Peter B Bitterman; Fiscal Year: 2011
    ..This information has the potential to lead to new treatments for all scarring diseases by revealing new molecular targets for antifibrotic therapy. ..
  2. Translational partitioning of the SL RNA
    David A Campbell; Fiscal Year: 2010
    ..This RNA and mode of splicing is not found in humans and represents a unique target for chemotherapy. ..
  3. Hyperglycemia-induced translational control of gene expression in the retina
    Michael D Dennis; Fiscal Year: 2013
    ..abstract_text> ..
  4. Assays for Discovery of Translation Inhibitors
    Gerhard Wagner; Fiscal Year: 2009
    ..The proposed study will allow us to obtain leads for anti-cancer and anti-viral drug design. ..
  5. REGULATION OF LIVER GROWTH AND FUNCTION
    Leonard S Jefferson; Fiscal Year: 2013
    ..Knowledge gained from the project will provide insight into designing strategies for treatment of pathologies resulting from the maladapted whole body metabolism associated with obesity and diabetes. ..
  6. Molecular mechanism of 4E-binding proteins on heart failure development
    Yingjie Chen; Fiscal Year: 2013
    ..Our preliminary finding indicates that regulation of cap-dependent translation initiation by targeting 4E-binding proteins may be a novel therapeutic approach to treat CHF. ..
  7. The role of decapping factors in mRNP remodeling
    MARC ARRIBAS-LAYTON; Fiscal Year: 2013
    ..The targets of the Hat1-Rbbp7 complex will be identified and the role of their acetylation in the mRNP decay process will be studied through mutational analysis and Hat1-Rbbp7 depletion. ..
  8. Analysis of cap-dependent translational repression by microRNAs in oncogensis
    Carl D Novina; Fiscal Year: 2013
    ....
  9. Ribosomal scanning and initiation codon selection
    Tatyana V Pestova; Fiscal Year: 2013
    ..These studies will determine the molecular basis for key events in translation initiation, and its regulation by trans-acting factors, which is a prerequisite for the development of rational therapies to treat such diseases. ) ..
  10. Defining the role of eIF4F in metastatic castration resistant prostate cancer
    ANDREW CALEB HSIEH; Fiscal Year: 2013
    ..Ultimately, the outstanding training that he will receive as a K08 awardee will provide him with a solid foundation to initiate an independent research program as a physician-scientist. ! ..
  11. Selective Degradation of mRNA by Herpes Simplex Virus 1
    Bernard Roizman; Fiscal Year: 2013
    ..Finally, given the multiple functions of VHS, the question arises as to the extent to which each function contributes to the pathogenic potential of HSV-1. ..
  12. CONTROL OF TRANSLATION IN HERPESVIRUS INFECTED CELLS
    IAN J MOHR; Fiscal Year: 2013
    ..define the mechanism(s) by which PABP abundance is controlled translationally in HCMV-infected cells;and iii) evaluate the role of cellular eIF4E-kinases &eIF4E phosphorylation on viral replication &pathogenesis ..
  13. Formation and regulation of the translating mRNP
    DAVID ERIC WEINBERG; Fiscal Year: 2013
    ..Collectively, these aims will improve our knowledge of cellular translation mechanisms and our understanding of how these mechanisms go awry in disease. ..
  14. Development of Translation Initiation Inhibitors and their Anti-Cancer Activity
    Michael Chorev; Fiscal Year: 2012
    ....
  15. The role of host and viral translation factors during HCMV infection
    Nathaniel J Moorman; Fiscal Year: 2013
    ..These drugs would allow for the continued synthesis of antiviral host proteins, and would have reduced toxicity due to their specificity for infected cells. ..
  16. Signal Transduction of Type 1 Interferons in Malignant Cells
    Leonidas C Platanias; Fiscal Year: 2013
    ..Ultimately, they may form the basis for new approaches to overcome IFN-resistance. ..
  17. Characterization of hantavirus N protein-mediated translation mechanism
    MOHAMMAD AYOUB MIR; Fiscal Year: 2013
    ..The proposed studies will also reveal novel targets for antiviral drug design in future. ..
  18. Ras-Induced Autophagic Growth-Arrest in Immortalized Human Epithelial Cells
    JOSE GOMEZ-GARCIA; Fiscal Year: 2011
    ..This work provides the opportunity to study negative regulators of autophagy as a novel avenue of new targets for therapeutics or chemo-preventive agents to improve human health. ..
  19. Translational Control of Breast Cancer
    Vitaly A Polunovsky; Fiscal Year: 2010
    ....
  20. Translational Regulation of the Inflammatory Breast Cancer Stem Cell
    Deborah Silvera; Fiscal Year: 2012
    ....
  21. Mechanisms of activation of human mRNA decapping
    Jens Lykke-Andersen; Fiscal Year: 2013
    ..This should provide fundamental new insights into mechanisms of mRNA regulation, which when deregulated can lead to disease. ..
  22. Translational Apparatus as a Target for Drug Discovery
    Vitaly Polunovsky; Fiscal Year: 2004
    ..To achieve these aims, we have assembled an experienced investigative team committed to anticancer drug discovery . ..
  23. Control of elF4F complex by Vesicular Stomatitis Virus
    John Connor; Fiscal Year: 2007
    ....
  24. 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. ..
  25. Alcohol-Induced Regulation of Hepatic Protein Synthesis
    THOMAS VARY; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  26. MYOCARDIAL PROTEIN SYNTHESIS AFTER ALCOHOL INTOXICATION
    Charles H Lang; Fiscal Year: 2010
    ..Overall, the research design will establish the mechanism by which myocardial protein synthesis is reduced in response to alcohol abuse. ..
  27. Antiretroviral-Induced Defects in Muscle Protein Synthesis
    Charles H Lang; Fiscal Year: 2010
    ..Such data is needed to both realize the full potential and avoid possible pitfalls of this drug in the long-term treatment of HIV-infected individuals. ..
  28. Myocardial Protein Synthesis After Thermal Injury
    Charles Lang; Fiscal Year: 2005
    ..Overall, the research will elucidate the mechanisms by which myocardial protein synthesis is reduced after thermal injury, leading to the better understanding and treatment of the resulting cardiomyopathy. - ..
  29. REGULATION OF PROTEIN TURNOVER IN SEPSIS
    Scot R Kimball; Fiscal Year: 2010
    ....
  30. Nutritional Regulation of Fetal Liver Development
    PHILIP GRUPPUSO; Fiscal Year: 2008
    ..Furthermore, we anticipate that our findings will relate to diverse areas of liver biology, including the hepatic response to liver injury, hepatic carcinogenesis, and liver stem cell biology. [unreadable] [unreadable]..
  31. Internal Initiation in the Translation of Cellular mRNAs
    Vincent Mauro; Fiscal Year: 2004
    ....
  32. Role of Vpu in HIV1 Particle Exit
    Antonito Panganiban; Fiscal Year: 2004
    ..Additional genetic experiments will be carried out to determine the nature of second site revertants that arise following the propagation of primary Vpu mutants. ..
  33. RESEARCH TRAINING IN PHYSIOLOGICAL ADAPTATION TO STRESS
    Leonard Jefferson; Fiscal Year: 2005
    ..abstract_text> ..
  34. Mechanism of ribosomal subunit joining in eukaryotes
    Tatyana Pestova; Fiscal Year: 2005
    ....
  35. IMPROVED TECHNOLOGIES FOR FULL LENGTH CDNA GENERATION
    Jerry Pelletier; Fiscal Year: 2001
    ..Together, these studies should yield higher quality cDNA libraries that can provide an important resource for novel gene discovery and provide reagents necessary for functional studies. ..
  36. Hepatocyte Proliferation During Development: Role of p38
    PHILIP GRUPPUSO; Fiscal Year: 2006
    ..We anticipate that these studies will provide novel insights into the regulation of hepatocyte proliferation during normal development and in the mature rat. ..
  37. The Unfolded Protein Response After Brain Ischemia
    DONALD DEGRACIA; Fiscal Year: 2006
    ..abstract_text> ..
  38. Hantavirus RNA Encapsidation
    Antonito Panganiban; Fiscal Year: 2006
    ..abstract_text> ..
  39. High Throughput Assays Targeting Ribosome Recruitment
    Jerry Pelletier; Fiscal Year: 2007
    ..abstract_text> ..
  40. Screening for Small Molecule Inhibitors of Eukaryotic Translation Initiation
    Jerry Pelletier; Fiscal Year: 2007
    ..Should any of the optimized hits show activity in vivo, relative cytotoxicities will be determined in lymphomas of defined genotypes generated from a mechanism-based mouse cancer model. [unreadable] [unreadable] [unreadable]..
  41. Cis- and Trans-acting Factors in HCV Gene Expression
    Shelton Bradrick; Fiscal Year: 2008
    ..abstract_text> ..
  42. Interdicting Eukaryotic Translation Initiation Factor-RNA Interaction
    Jerry Pelletier; Fiscal Year: 2008
    ..In addition, since this target of these compounds resides downstream of the target of rapamycin (called TOR), these may be of use against rapamycin-resistant cancers. [unreadable] [unreadable] [unreadable]..
  43. Role of RNA Structural Switches in the Replication of a (+)-Strand RNA Virus
    ANNE ELIZABETH SIMON; Fiscal Year: 2010
    ....
  44. Regulation of translation initiation in eukaryotes
    Vincent P Mauro; Fiscal Year: 2010
    ..g. for the production of therapeutic proteins, and new avenues for analyzing the potential contributions of mis-regulation to disease. ..
  45. HIV-1 RNA ENCAPSIDATION, DIMER FORMATION, AND STRUCTURE
    Antonito Panganiban; Fiscal Year: 2002
    ..We hope to develop a comprehensive picture that helps us understand in and exact way how correct encapsidation and dimer formation lead to correct reverse transcription. ..