prokaryotic initiation factor 2

Summary

Summary: The largest of the three prokaryotic initiation factors with a molecular size of approximately 80 kD. It functions in the transcription initiation process by promoting the binding of formylmethionine-tRNA to the P-site of the 30S ribosome and by preventing the incorrect binding of elongator tRNA to the translation initiation site.

Top Publications

  1. pmc Interleukin 3 stimulates protein synthesis by regulating double-stranded RNA-dependent protein kinase
    T Ito
    Johns Hopkins Oncology Center, Baltimore, MD 21231
    Proc Natl Acad Sci U S A 91:7455-9. 1994
  2. ncbi Promotion of met-tRNAiMet binding to ribosomes by yIF2, a bacterial IF2 homolog in yeast
    S K Choi
    Laboratory of Eukaryotic Gene Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892 2716, USA
    Science 280:1757-60. 1998
  3. ncbi Initiation factor IF2, thiostrepton and micrococcin prevent the binding of elongation factor G to the Escherichia coli ribosome
    Dale M Cameron
    School of Microbiology and Immunology, University of New South Wales, Sydney, NSW 2052, Australia
    J Mol Biol 319:27-35. 2002
  4. pmc Unfolded protein response in fuchs endothelial corneal dystrophy: a unifying pathogenic pathway?
    Christoph Engler
    Wilmer Eye Institute, The Johns Hopkins Medical Institutions, 600 North Wolfe Street, Baltimore, MD 21287, USA
    Am J Ophthalmol 149:194-202.e2. 2010
  5. pmc Selective stimulation of translation of leaderless mRNA by initiation factor 2: evolutionary implications for translation
    S Grill
    Institute of Microbiology and Genetics, Vienna Biocenter, University of Vienna, Dr Bohrgasse 9, 1030 Vienna, Austria
    EMBO J 19:4101-10. 2000
  6. ncbi Phosphorylation of initiation factor 2 alpha by protein kinase GCN2 mediates gene-specific translational control of GCN4 in yeast
    T E Dever
    Section on Molecular Genetics of Lower Eukaryotes, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892
    Cell 68:585-96. 1992
  7. ncbi Involvement of 16S rRNA nucleotides G1338 and A1339 in discrimination of initiator tRNA
    Laura Lancaster
    Department of Molecular, Cell and Developmental Biology and The Center for Molecular Biology of RNA, University of California, Santa Cruz, Santa Cruz, California 95064, USA
    Mol Cell 20:623-32. 2005
  8. ncbi Kinetic checkpoint at a late step in translation initiation
    Pohl Milon
    Department of Biology MCA, Laboratory of Genetics, University of Camerino, 62032 Camerino, Italy
    Mol Cell 30:712-20. 2008
  9. ncbi The cryo-EM structure of a translation initiation complex from Escherichia coli
    Gregory S Allen
    Howard Hughes Medical Institute, Health Research, Inc at the Wadsworth Center, Albany, New York 12201, USA
    Cell 121:703-12. 2005
  10. ncbi Translation initiation factor IF2 interacts with the 30 S ribosomal subunit via two separate binding sites
    Enrico Caserta
    Laboratory of Genetics, Department of Biology, University of Camerino, 62032 Camerino MC, Italy
    J Mol Biol 362:787-99. 2006

Detail Information

Publications212 found, 100 shown here

  1. pmc Interleukin 3 stimulates protein synthesis by regulating double-stranded RNA-dependent protein kinase
    T Ito
    Johns Hopkins Oncology Center, Baltimore, MD 21231
    Proc Natl Acad Sci U S A 91:7455-9. 1994
    ..Thus, IL-3 appears to positively regulate protein synthesis by inducing the inactivation of PKR in a growth factor signaling pathway...
  2. ncbi Promotion of met-tRNAiMet binding to ribosomes by yIF2, a bacterial IF2 homolog in yeast
    S K Choi
    Laboratory of Eukaryotic Gene Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892 2716, USA
    Science 280:1757-60. 1998
    ..Thus, the mechanism of protein synthesis in eukaryotes and prokaryotes is more similar than was previously realized...
  3. ncbi Initiation factor IF2, thiostrepton and micrococcin prevent the binding of elongation factor G to the Escherichia coli ribosome
    Dale M Cameron
    School of Microbiology and Immunology, University of New South Wales, Sydney, NSW 2052, Australia
    J Mol Biol 319:27-35. 2002
    ..Micrococcin stimulates GTP hydrolysis by both factors. We show directly that these drugs act by destabilizing the interaction of EF-G with the ribosome, and provide evidence that they have similar effects on IF2...
  4. pmc Unfolded protein response in fuchs endothelial corneal dystrophy: a unifying pathogenic pathway?
    Christoph Engler
    Wilmer Eye Institute, The Johns Hopkins Medical Institutions, 600 North Wolfe Street, Baltimore, MD 21287, USA
    Am J Ophthalmol 149:194-202.e2. 2010
    ..To assess for activation of the unfolded protein response in corneal endothelium of Fuchs endothelial corneal dystrophy patients...
  5. pmc Selective stimulation of translation of leaderless mRNA by initiation factor 2: evolutionary implications for translation
    S Grill
    Institute of Microbiology and Genetics, Vienna Biocenter, University of Vienna, Dr Bohrgasse 9, 1030 Vienna, Austria
    EMBO J 19:4101-10. 2000
    ....
  6. ncbi Phosphorylation of initiation factor 2 alpha by protein kinase GCN2 mediates gene-specific translational control of GCN4 in yeast
    T E Dever
    Section on Molecular Genetics of Lower Eukaryotes, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892
    Cell 68:585-96. 1992
    ..Thus, an established mechanism for regulating total protein synthesis in mammalian cells mediates gene-specific translational control in yeast...
  7. ncbi Involvement of 16S rRNA nucleotides G1338 and A1339 in discrimination of initiator tRNA
    Laura Lancaster
    Department of Molecular, Cell and Developmental Biology and The Center for Molecular Biology of RNA, University of California, Santa Cruz, Santa Cruz, California 95064, USA
    Mol Cell 20:623-32. 2005
    ..Moreover, our findings indicate that discrimination also involves recognition of at least one additional feature of the tRNA(fMet) anticodon stem loop...
  8. ncbi Kinetic checkpoint at a late step in translation initiation
    Pohl Milon
    Department of Biology MCA, Laboratory of Genetics, University of Camerino, 62032 Camerino, Italy
    Mol Cell 30:712-20. 2008
    ....
  9. ncbi The cryo-EM structure of a translation initiation complex from Escherichia coli
    Gregory S Allen
    Howard Hughes Medical Institute, Health Research, Inc at the Wadsworth Center, Albany, New York 12201, USA
    Cell 121:703-12. 2005
    ..Additionally, we present evidence for the localization of IF1, IF3, one C-terminal domain of L7/L12, and the N-terminal domain of IF2 in the initiation complex...
  10. ncbi Translation initiation factor IF2 interacts with the 30 S ribosomal subunit via two separate binding sites
    Enrico Caserta
    Laboratory of Genetics, Department of Biology, University of Camerino, 62032 Camerino MC, Italy
    J Mol Biol 362:787-99. 2006
    ....
  11. pmc A quantitative kinetic scheme for 70 S translation initiation complex formation
    Christina Grigoriadou
    Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Mol Biol 373:562-72. 2007
    ..GDPCP does not affect stable 70 S formation, but perturbs fMet-tRNA(fMet) positioning in the P-site. In contrast, thiostrepton severely retards stable 70 S formation, but allows normal binding of fMet-tRNA(fMet)(prf20) to the P-site...
  12. ncbi Conformational transition of initiation factor 2 from the GTP- to GDP-bound state visualized on the ribosome
    Alexander G Myasnikov
    Department of Structural Biology and Genomics, Institute of Genetics and Molecular and Cellular Biology, Centre National de la Recherche Scientifique Institut National de la Santé et de la Recherche Médicale, Universite Louis Pasteur, Illkirch, France
    Nat Struct Mol Biol 12:1145-9. 2005
    ..Our data also provide insights into the molecular mechanism guiding release of IF1 and IF3...
  13. pmc The translational fidelity function of IF3 during transition from the 30 S initiation complex to the 70 S initiation complex
    Christina Grigoriadou
    Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Mol Biol 373:551-61. 2007
    ....
  14. ncbi Structure of the 30S translation initiation complex
    Angelita Simonetti
    Institute of Genetics and of Molecular and Cellular Biology, Department of Structural Biology and Genomics, Illkirch F 67404, France
    Nature 455:416-20. 2008
    ....
  15. ncbi Modulation of ribosomal recruitment to 5'-terminal start codons by translation initiation factors IF2 and IF3
    S Grill
    Institute of Microbiology and Genetics, Vienna Biocenter, University of Vienna, Austria
    FEBS Lett 495:167-71. 2001
    ....
  16. ncbi The Pseudomonas aeruginosa initiation factor IF-2 is responsible for formylation-independent protein initiation in P. aeruginosa
    Marta Steiner-Mosonyi
    Department of Molecular and Cellular Biology, University of Guelph, Ontario N1G 2W1, Canada
    J Biol Chem 279:52262-9. 2004
    ..Furthermore these findings give important clues to the basis for discriminating the initiator Met-tRNA by IF-2 and for the evolution of alternative mechanisms for discrimination...
  17. ncbi Correlation of phylogenetic lineages of group B Streptococci, identified by analysis of restriction-digestion patterns of genomic DNA, with infB alleles and mobile genetic elements
    Shinji Takahashi
    Division of Microbiology, Joshi Eiyoh University, Chiyoda, Sakado, Saitama, Japan
    J Infect Dis 186:1034-8. 2002
    ..These molecular markers can be used to identify GBS populations and to correlate RDP types and phylogenetic lineages identified by different methods...
  18. ncbi Mutants of Escherichia coli initiator tRNA defective in initiation. Effects of overproduction of methionyl-tRNA transformylase and the initiation factors IF2 and IF3
    D Mangroo
    Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA
    J Biol Chem 270:12203-9. 1995
    ..mRNA.fMet-tRNA initiation complex in Escherichia coli. Over-production of IF3 did not affect the initiator activity of any of the tRNA mutants studied...
  19. ncbi Interplay of methionine tRNAs with translation elongation factor Tu and translation initiation factor 2 in Escherichia coli
    J M Guillon
    Laboratoire de Biochimie, URA CNRS 1970, Ecole Polytechnique, F91128 Palaiseau Cedex, France
    J Biol Chem 271:22321-5. 1996
    ..M., Mechulam, Y., Schmitter, J.-M., Blanquet, S., and Fayat, G. (1992) J. Bacteriol. 174, 4294-4301...
  20. ncbi How initiation factors maximize the accuracy of tRNA selection in initiation of bacterial protein synthesis
    Ayman Antoun
    Department of Cell and Molecular Biology, Biomedical Centre, Uppsala University, S 751 24 Uppsala, Sweden
    Mol Cell 23:183-93. 2006
    ..We suggest why IF1 is essential for E. coli, discuss the role of the G-C base pairs in the anticodon stem of some tRNAs, and clarify gene expression changes with varying IF3 concentration in the living cell...
  21. ncbi Investigation of the translation-initiation factor IF2 gene, infB, as a tool to study the population structure of Streptococcus agalactiae
    J Hedegaard
    Department of Biostructural Chemistry, Institute of Molecular and Structural Biology, Aarhus University, Gustav Wiedsvej 10C, DK 8000 Aarhus C, Denmark
    Microbiology 146:1661-70. 2000
    ..agalactiae, yielding an evolutionary tree which had a topology similar to a tree constructed using 16S rRNA sequences from the same species...
  22. pmc Ribosomal localization of translation initiation factor IF2
    Stefano Marzi
    Laboratory of Genetics, Department of Biology MCA, University of Camerino, 62032 Camerino MC Italy
    RNA 9:958-69. 2003
    ..Comparison of our present findings with previous data further suggests that the IF2 orientation on the 30S subunit changes during the transition from the 30S to 70S initiation complex...
  23. ncbi Peptidyl-tRNA regulates the GTPase activity of translation factors
    Andrey V Zavialov
    Department of Cell and Molecular Biology, BMC, Uppsala University, Box 596, S 75124 Uppsala, Sweden
    Cell 114:113-22. 2003
    ..We also propose a model for translocation of tRNAs in two separate steps, which clarifies the roles of EF-G.GTP and GTP hydrolysis in this process...
  24. ncbi Multidomain initiation factor 2 from Thermus thermophilus consists of the individual autonomous domains
    Gabriel Zoldak
    Department of Biochemistry, Faculty of Sciences, P J Safarik University, Kosice, Slovakia
    Biochemistry 47:4992-5005. 2008
    ..In conclusion, interactions between the domains of folded IF2wt in vivo are likely mediated by their alpha-helix connection and/or by a conformational change on the ribosome...
  25. ncbi Solution structure of C-terminal Escherichia coli translation initiation factor IF2 by small-angle X-ray scattering
    Louise Carøe Vohlander Rasmussen
    Department of Molecular Biology, Centre for mRNP Biogenesis and Metabolism, University of Aarhus, DK 8000 Aarhus C, Denmark
    Biochemistry 47:5590-8. 2008
    ..The chalice-like structure with a highly exposed alpha-helical stretch observed for the aIF5B crystal structure was not found in the structural model of IF2 in solution, in which domain VI-2 is moved closer to the rest of the protein...
  26. ncbi Cloning and sequencing of the homologues of both the bacterial and eukaryotic initiation factor genes (hIF-2 and heIF-2 gamma) from archaeal Halobacterium halobium
    Y Hasegawa
    Department of Bioresource Development, Hiroshima Prefectural University, Japan
    Biochem Mol Biol Int 46:495-507. 1998
    ..The sequence of hIF-2 shows a strong similarity to the initiation factor IF-2 from Bacteria whereas heIF-2 gamma shows a strong similarity to the initiation factor eIF-2 gamma from Eucarya...
  27. ncbi Characterization of mutations in the GTP-binding domain of IF2 resulting in cold-sensitive growth of Escherichia coli
    Brian Søgaard Laursen
    Department of Molecular Biology, Aarhus University, DK 8000 C Aarhus, Denmark
    J Mol Biol 326:543-51. 2003
    ..The results indicate that the amino acid residues, Asp409 and Gly422, are located in important regions of the IF2 G-domain and demonstrate the importance of GTP hydrolysis in translation initiation for optimal cell growth...
  28. ncbi A conserved structural motif at the N terminus of bacterial translation initiation factor IF2
    Brian Søgaard Laursen
    Department of Molecular Biology, University of Aarhus, DK 8000 Aarhus, Denmark
    J Biol Chem 278:16320-8. 2003
    ..The results of the present work will provide guidance for the design of future experiments directed toward understanding the functional roles of this widely conserved structural domain within IF2...
  29. ncbi Inhibition of bacterial IF2 binding to fMet-tRNA((fMet)) by aminoglycosides
    J M Evans
    Global High Throughput Screening, Pharmacia Corp, Kalamazoo, MI 49007, USA
    Bioorg Med Chem Lett 13:993-6. 2003
    ..This hypothesis is further supported by isothermal denaturation experiments that failed to show any interaction between the IF2 protein and the aminoglycosides...
  30. ncbi Uncoupling of initiation factor eIF5B/IF2 GTPase and translational activities by mutations that lower ribosome affinity
    Byung Sik Shin
    Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Cell 111:1015-25. 2002
    ..The translational defect suggests eIF5B stabilizes Met-tRNA(i)(Met) binding and that GTP hydrolysis by eIF5B is a checkpoint monitoring 80S ribosome assembly in the final step of translation initiation...
  31. pmc Separate domains in GCN1 for binding protein kinase GCN2 and ribosomes are required for GCN2 activation in amino acid-starved cells
    E Sattlegger
    Laboratory of Eukaryotic Gene Regulation, National Institute of Child Health and Human Development, National Institutes of Health, 6 Center Drive, Building 6A, Room B1A 13, Bethesda, MD 20892 2759, USA
    EMBO J 19:6622-33. 2000
    ..GCN1 expression conferred sensitivity to paromomycin in a manner dependent on its ribosome binding domain, supporting the idea that GCN1 binds near the ribosomal acceptor site to promote GCN2 activation by uncharged tRNA...
  32. ncbi The fate of the initiator tRNAs is sensitive to the critical balance between interacting proteins
    S Thanedar
    Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560 012, India
    J Biol Chem 275:20361-7. 2000
    ..These findings provide an important clue to understand the dual function of the single tRNA(Met) in initiation and elongation, in the mitochondria of various organisms...
  33. pmc Initiation factor 2 of Myxococcus xanthus, a large version of prokaryotic translation initiation factor 2
    E Tiennault-Desbordes
    Institut de Biologie Moléculaire et d Ingénierie Génétique, ESA CNRS 6031, Universite de Poitiers, 86022 Poitiers Cedex, France
    J Bacteriol 183:207-13. 2001
    ..The second is unique to M. xanthus IF2, is located between the APE sequence and the GTP binding domain, and consists exclusively of glycine, proline, and arginine residues...
  34. ncbi A cDNA for nuclear-encoded chloroplast translational initiation factor 2 from a higher plant is able to complement an infB Escherichia coli null mutant
    F Campos
    Departamento de Biologia Molecular de Plantas del Instituto de Biotecnologia, , A. P. 510-3, Cuernavaca, Morelos 62250,
    J Biol Chem 276:28388-94. 2001
    ..Phylogenetic analysis using the PvIF2cp conserved region suggests that the PvIF2cp gene originated via endosymbiotic gene transfer to the nucleus and that it may be a useful marker for phylogeny reconstruction...
  35. ncbi Chaperone properties of bacterial elongation factor EF-G and initiation factor IF2
    T Caldas
    Biochimie Génétique, Institut Jacques Monod, Universite Paris 7, 2 place Jussieu, 75005 Paris, France
    J Biol Chem 275:855-60. 2000
    ..These results suggest that EF-G and IF2, in addition to their role in translation, might be implicated in protein folding and protection from stress...
  36. ncbi Conservation of bacterial protein synthesis machinery: initiation and elongation in Mycobacterium smegmatis
    Christian M Bruell
    Institute of Medical Microbiology, University of Zurich, Switzerland
    Biochemistry 47:8828-39. 2008
    ..smegmatis components as an alternative to that from E. coli to study the mechanisms of translation and to test the action of antibiotics against Gram-positive bacteria...
  37. pmc Cloning and characterization of hIF2, a human homologue of bacterial translation initiation factor 2, and its interaction with HIV-1 matrix
    S A Wilson
    Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, U K
    Biochem J 342:97-103. 1999
    ..hIF2 does not correspond to any of the previously characterized translation initiation factors identified in mammals, but its essential role in translation appears to have been conserved from bacteria to humans...
  38. pmc Universal conservation in translation initiation revealed by human and archaeal homologs of bacterial translation initiation factor IF2
    J H Lee
    Laboratory of Eukaryotic Gene Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892 2716, USA
    Proc Natl Acad Sci U S A 96:4342-7. 1999
    ..We propose a universally conserved function for IF2 in facilitating the proper binding of initiator methionyl-tRNA to the ribosomal P site...
  39. ncbi Thermodynamic analysis reveals that GTP binding affects the interaction between the alpha- and gamma-subunits of translation initiation factor 2
    Makoto Nakakido
    Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 301 FBS Building, 5 1 5 Kashiwanoha, Kashiwa 277 8562, Japan
    Biochem Biophys Res Commun 371:596-9. 2008
    ..These results suggest that the binding of both the alpha-subunit and GTP changes the conformation of the switch region of the gamma-subunit and increases the affinity of the gamma-subunit for tRNA...
  40. ncbi [Interaction of 23S ribosomal RNA helices 89 and 91 of Escherichia coli contributes to the activity of IF2 but is insignificant for elongation factors functioning]
    D E Burakovskiĭ
    Mol Biol (Mosk) 41:1031-41. 2007
    ..Thus, the contact between helices 89 and 91 is important for efficient IF2 functioning in translation initiation...
  41. ncbi New insights into the interactions of the translation initiation factor 2 from archaea with guanine nucleotides and initiator tRNA
    Oleg Nikonov
    Institute of Protein Research, Russian Academy of Sciences, 142290 Pushchino, Moscow Region, Russian Federation
    J Mol Biol 373:328-36. 2007
    ..Thus, this model is in good agreement with experimental data showing that the alpha subunit of aIF2 is necessary for the stable interaction of aIF2gamma with Met-tRNA i Met...
  42. pmc The RNA chain elongation rate in Escherichia coli depends on the growth rate
    U Vogel
    Department of Biological Chemistry, University of Copenhagen, Denmark
    J Bacteriol 176:2807-13. 1994
    ..However, the untranslated RNA chain specified by the rrnB gene was elongated nearly twice as fast as the two mRNA species encoded by infB and lacZ...
  43. ncbi Crystal structure of the ternary complex of Phe-tRNAPhe, EF-Tu, and a GTP analog
    P Nissen
    Department of Biostructural Chemistry, Institute of Chemistry, Aarhus University, Denmark
    Science 270:1464-72. 1995
    ..The overall shape of the ternary complex is similar to that of the translocation factor, EF-G-GDP, and this suggests a novel mechanism involving "molecular mimicry" in the translational apparatus...
  44. ncbi Pisum sativum contains a factor with strong homology to eIF5B
    Sheeba Rasheedi
    Laboratory of Molecular and Cellular Biology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad 500 076, India
    Gene 399:144-51. 2007
    ..Pfam domain search analysis pointed to its likely role as a translation initiation factor. The presence of an eIF5B-like factor in a plant system will aid in better understanding of the mechanism of translation initiation in plants...
  45. ncbi The ribosomal stalk binds to translation factors IF2, EF-Tu, EF-G and RF3 via a conserved region of the L12 C-terminal domain
    Magnus Helgstrand
    Department of Biophysical Chemistry, Lund University, Box 124, SE 22100 Lund, Sweden
    J Mol Biol 365:468-79. 2007
    ..These results indicate that the L12-factor complexes will be highly populated on the ribosome, because of the high local concentration of ribosome-bound factor with respect to L12...
  46. pmc Isolation and molecular genetic characterization of the Bacillus subtilis gene (infB) encoding protein synthesis initiation factor 2
    K Shazand
    Institut de Biologie Physico Chimique, Paris, France
    J Bacteriol 172:2675-87. 1990
    ..subtilis chromosome, between the polC and spcB loci. This location is distinct from those of the other major ribosomal protein and rRNA gene clusters of B. subtilis...
  47. ncbi Initiator tRNA binding by e/aIF5B, the eukaryotic/archaeal homologue of bacterial initiation factor IF2
    Laurent Guillon
    Laboratoire de Biochimie, Unité Mixte de Recherche 7654, CNRS Ecole Polytechnique, F 91128 Palaiseau cedex, France
    Biochemistry 44:15594-601. 2005
    ..Recognition of an aminoacylated tRNA species at this site would then allow translation to begin. In the case of archaea, this checkpoint would also include the verification of the presence of a methionine at the P site...
  48. ncbi Structural and functional domains of E coli initiation factor IF2
    S Laalami
    Institut de Biologie Physico Chimique, Paris, France
    Biochimie 73:1557-66. 1991
    ..Here we review evidence which indicates the functional importance of the different structural domains of IF2, emphasizing new information obtained by in vivo experiments...
  49. ncbi Tandem translation of E. coli initiation factor IF2 beta: purification and characterization in vitro of two active forms
    N R Nyengaard
    Dept of Chemistry, Aarhus University, Denmark
    Biochem Biophys Res Commun 181:1572-9. 1991
    ..In this assay no difference in activity is detected...
  50. pmc The nucleotide-binding site of bacterial translation initiation factor 2 (IF2) as a metabolic sensor
    Pohl Milon
    Laboratory of Genetics, Department of Biology MCA, University of Camerino, 62032 Camerino MC, Italy
    Proc Natl Acad Sci U S A 103:13962-7. 2006
    ....
  51. ncbi Cloning and sequence analysis of the cDNA for bovine mitochondrial translational initiation factor 2
    J Ma
    Department of Chemistry, University of North Carolina at Chapel Hill, USA
    Biochim Biophys Acta 1261:321-4. 1995
    ..The open reading frame for bovine IF-2mt encodes a protein of 727 amino acids. The sequence of bovine IF-2mt exhibits 85% identity to human IF-2mt, but only 38% identity to yeast IF-2mt and 39% identity to Escherichia coli IF-2 alpha...
  52. ncbi Mitochondrial initiation factor 2 of Trypanosoma brucei binds imported formylated elongator-type tRNA(Met)
    Fabien Charrière
    Department of Biology Zoology, University of Fribourg, Chemin du Musee 10, CH 1700 Fribourg, Switzerland
    J Biol Chem 280:15659-65. 2005
    ..Thus, these experiments illustrate the importance of mitochondrial translation initiation for growth of procyclic T. brucei...
  53. pmc The N-terminal domain (IF2N) of bacterial translation initiation factor IF2 is connected to the conserved C-terminal domains by a flexible linker
    Brian Søgaard Laursen
    Department of Molecular Biology, University of Aarhus, Aarhus, Denmark
    Protein Sci 13:230-9. 2004
    ..The features of structurally well-ordered N- and C-terminal domains connected by a flexible linker with significant helical content are reminiscent of another translation initiation factor, IF3...
  54. ncbi The translation initiation functions of IF2: targets for thiostrepton inhibition
    Letizia Brandi
    Laboratory of Genetics, Department of Biology MCA, University of Camerino, 62032 Camerino MC, Italy
    J Mol Biol 335:881-94. 2004
    ..Overall, our data indicate that the translation initiation function of IF2 is as sensitive as the translocation function of EF-G to thiostrepton inhibition...
  55. pmc Similar organization of the nusA-infB operon in Bacillus subtilis and Escherichia coli
    K Shazand
    Institut de Biologie Physico Chimique, Paris, France
    J Bacteriol 175:2880-7. 1993
    ..subtilis infB operons suggests that the function of each gene pair is conserved and that the B. subtilis NusA homolog, which is 124 residues shorter than its E. coli counterpart, could play a role similar to its role in E. coli...
  56. ncbi Functional molecular mapping of archaeal translation initiation factor 2
    Laure Yatime
    Laboratoire de Biochimie, Unité Mixte de Recherche 7654, CNRS Ecole Polytechnique, F 91128 Palaiseau cedex, France
    J Biol Chem 279:15984-93. 2004
    ..However, the N-domain of aIF2alpha interacts with RNA unspecifically. Based on this property, a possible contribution of aIF2alpha to formation of a productive complex between aIF2 and the small ribosomal subunit is envisaged...
  57. ncbi A favorable solubility partner for the recombinant expression of streptavidin
    Hans Peter Sørensen
    Laboratory of BioDesign, Department of Molecular Biology, Aarhus University, Gustav Wieds Vej 10 C, DK 8000 Aarhus C, Denmark
    Protein Expr Purif 32:252-9. 2003
    ..coli...
  58. pmc A single mammalian mitochondrial translation initiation factor functionally replaces two bacterial factors
    Rahul Gaur
    Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India
    Mol Cell 29:180-90. 2008
    ..However, in this background, IF1 remains essential. These observations provide strong evidence that a single factor (IF2(mt)) in mammalian mitochondria performs the functions of two eubacterial factors, IF1 and IF2...
  59. pmc Genetic interaction screens with ordered overexpression and deletion clone sets implicate the Escherichia coli GTPase YjeQ in late ribosome biogenesis
    Tracey L Campbell
    Antimicrobial Research Centre and Department of Biochemistry and Biomedical Sciences, McMaster University, 1200 Main St West, Hamilton, Ontario, Canada L8N 3Z5
    J Bacteriol 190:2537-45. 2008
    ..Taken in context, our work is most consistent with the hypothesis that YjeQ has a role in late 30S subunit biogenesis...
  60. pmc Requirements for translation re-initiation in Escherichia coli: roles of initiator tRNA and initiation factors IF2 and IF3
    Jae Ho Yoo
    Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Mol Microbiol 67:1012-26. 2008
    ..Strikingly, overexpression of IF3 also blocked E. coli from acting as a host for propagation of M13 phage...
  61. ncbi The interaction of mitochondrial translational initiation factor 2 with the small ribosomal subunit
    Angela C Spencer
    Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 3290, USA
    Biochim Biophys Acta 1750:69-81. 2005
    ..Mutations in this region caused a significant reduction in the ability of the factor to promote initiation complex formation and to bind 28S subunits...
  62. pmc Casein kinase II mediates multiple phosphorylation of Saccharomyces cerevisiae eIF-2 alpha (encoded by SUI2), which is required for optimal eIF-2 function in S. cerevisiae
    L Feng
    Department of Biology, Indiana University, Bloomington 47405
    Mol Cell Biol 14:5139-53. 1994
    ..These genetic data appear to indicate that the modifications that we describe at the carboxyl end of the eIF-2 alpha protein are required for optimal eIF-2 function in S. cerevisiae...
  63. ncbi Type 1 phosphatase inhibitors reduce the restoration of guanine nucleotide exchange activity of eukaryotic initiation factor 2B inhibited reticulocyte lysates rescued by hemin
    S V Babu
    Department of Biochemistry, School of Life Sciences, University of Hyderabad, India
    Arch Biochem Biophys 327:201-8. 1996
    ..These findings suggest that a type 1 phosphatase is involved in the recovery of eIF-2B activity and protein synthesis upon delayed addition of hemin to heme-deficient lysates...
  64. ncbi Mechanism of inhibition of peptide chain initiation by amino acid deprivation in perfused rat liver. Regulation involving inhibition of eukaryotic initiation factor 2 alpha phosphatase activity
    S R Kimball
    Department of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University, Hershey 17033
    J Biol Chem 266:1969-76. 1991
    ....
  65. pmc The suil suppressor locus in Saccharomyces cerevisiae encodes a translation factor that functions during tRNA(iMet) recognition of the start codon
    H J Yoon
    Department of Biology, Indiana University, Bloomington 47405
    Mol Cell Biol 12:248-60. 1992
    ..The simplest interpretation of these studies is that the sui1 suppressor gene defines an additional factor that functions in concert with eIF-2 to enable tRNAiMet to establish ribosomal recognition of an AUG initiator codon...
  66. ncbi Cloning and characterization of complementary DNA encoding the eukaryotic initiation factor 2-associated 67-kDa protein (p67)
    S Wu
    Department of Chemistry, University of Nebraska, Lincoln 68588
    J Biol Chem 268:10796-801. 1993
    ..The protein also exhibits significant sequence identity in the N-terminal region with human eIF-2 beta-subunit...
  67. ncbi Methionine deprivation regulates the S6K1 pathway and protein synthesis in avian QM7 myoblasts without activating the GCN2/eIF2 alpha cascade
    Sonia Métayer-Coustard
    INRA, UR83 Recherches Avicoles, Nouzilly, France
    J Nutr 140:1539-45. 2010
    ..These findings suggest that methionine exerts an effect on S6K1 signaling and protein synthesis in avian QM7 myoblasts through a mechanism partly independent of the global regulation via tRNA charging...
  68. ncbi Crystal structure of the regulatory subunit of archaeal initiation factor 2B (aIF2B) from hyperthermophilic archaeon Pyrococcus horikoshii OT3: a proposed structure of the regulatory subcomplex of eukaryotic IF2B
    Yoshimitsu Kakuta
    Laboratory of Biochemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School, Kyushu University, Fukuoka 812 8581, Japan
    Biochem Biophys Res Commun 319:725-32. 2004
    ..This structure suggests an architecture of the three subunits, alpha, beta, and delta, in the regulatory subcomplex within eIF2B...
  69. pmc Hepatic heme-regulated inhibitor (HRI) eukaryotic initiation factor 2alpha kinase: a protagonist of heme-mediated translational control of CYP2B enzymes and a modulator of basal endoplasmic reticulum stress tone
    Poulomi Acharya
    Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA
    Mol Pharmacol 77:575-92. 2010
    ....
  70. pmc Growing rats respond to a sulfur amino acid-deficient diet by phosphorylation of the alpha subunit of eukaryotic initiation factor 2 heterotrimeric complex and induction of adaptive components of the integrated stress response
    Angelos K Sikalidis
    Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA
    J Nutr 140:1080-5. 2010
    ..Taken together, our results indicate that rats fed the SAA-deficient diet had a prolonged activation of an eIF2alpha kinase that leads to upregulation of adaptive components of the ISR...
  71. ncbi Expression and purification of the subunits of human translational initiation factor 2 (eIF2): phosphorylation of eIF2 alpha and beta
    Rajasekhar N V S Suragani
    Department of Biochemistry, University of Hyderabad, Hyderabad 500 046, India
    Protein Expr Purif 47:225-33. 2006
    ..The recombinant subunits of eIF2alpha and beta-subunits were also phosphorylated in cultured insect cells. Phosphorylation of eIF2alpha in vitro was not significantly different in the presence and absence of the other subunits...
  72. pmc The beta/Gcd7 subunit of eukaryotic translation initiation factor 2B (eIF2B), a guanine nucleotide exchange factor, is crucial for binding eIF2 in vivo
    Kamal Dev
    Laboratory of Gene Regulation and Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA
    Mol Cell Biol 30:5218-33. 2010
    ..In aggregate, these findings provide compelling evidence that β/Gcd7 is crucial for binding of substrate by eIF2B in vivo, beyond its dispensable regulatory role in the inhibition of eIF2B by eIF (αP)...
  73. ncbi Gene-specific translational control of the yeast GCN4 gene by phosphorylation of eukaryotic initiation factor 2
    A G Hinnebusch
    Section on Molecular Genetics of Lower Eukaryotes, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892
    Mol Microbiol 10:215-23. 1993
    ..GTP.Met-tRNA(iMet) complexes by inhibiting the guanine nucleotide exchange factor for eIF-2, which is the same mechanism utilized in mammalian cells to inhibit total protein synthesis by phosphorylation of eIF-2...
  74. pmc Defects in tRNA processing and nuclear export induce GCN4 translation independently of phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2
    H Qiu
    Laboratory of Eukaryotic Gene Regulation, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA
    Mol Cell Biol 20:2505-16. 2000
    ..We propose that yeast contains a nuclear surveillance system that perceives defects in processing or export of tRNA and evokes a reduction in translation initiation at the step of initiator tRNA(Met) binding to the ribosome...
  75. pmc GCN2 protein kinase is required to activate amino acid deprivation responses in mice treated with the anti-cancer agent L-asparaginase
    Piyawan Bunpo
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Evansville, Indiana 47712, USA
    J Biol Chem 284:32742-9. 2009
    ..These results indicate that GCN2 is required for activation of AADR to asparaginase in liver. Rapamycin modifies the hepatic AADR to asparaginase by preventing CHOP induction while maximizing inhibition of mTORC1...
  76. pmc Dimerization by translation initiation factor 2 kinase GCN2 is mediated by interactions in the C-terminal ribosome-binding region and the protein kinase domain
    H Qiu
    Laboratory of Eukaryotic Gene Regulation, National Institute of Child Health and Human Development, Bethesda, Maryland 20892 2716, USA
    Mol Cell Biol 18:2697-711. 1998
    ..We propose that physical interactions between the PK domain and its flanking regulatory regions and dimerization through the PK and C-term domains both play important roles in restricting GCN2 kinase activity to amino acid-starved cells...
  77. pmc Identification and characterization of pancreatic eukaryotic initiation factor 2 alpha-subunit kinase, PEK, involved in translational control
    Y Shi
    Diabetes Research, Endocrine Division, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA
    Mol Cell Biol 18:7499-509. 1998
    ..We also identified PEK homologs from both Caenorhabditis elegans and the puffer fish Fugu rubripes, suggesting that this eIF-2alpha kinase plays an important role in translational control from nematodes to mammals...
  78. ncbi Reversible phosphorylation of eukaryotic initiation factor 2 alpha in response to endoplasmic reticular signaling
    C R Prostko
    Department of Pharmacology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway 08854
    Mol Cell Biochem 127:255-65. 1993
    ..We hypothesize that perturbation of the translocon, rather than suppression of protein processing, initiates the signal emanating from the ER culminating in eIF-2 alpha phosphorylation and translational repression...
  79. pmc A multifactor complex of eukaryotic initiation factors, eIF1, eIF2, eIF3, eIF5, and initiator tRNA(Met) is an important translation initiation intermediate in vivo
    K Asano
    Laboratory of Eukaryotic Gene Regulation, National Institute of Child Health and Human Development, NIH, Bethesda, Maryland 20892, USA
    Genes Dev 14:2534-46. 2000
    ..We propose that the multifactor complex is an important intermediate in translation initiation in vivo...
  80. ncbi A mechanistic model of nutritional control of protein synthesis in animal tissues
    Ehab R El-Haroun
    Centre for Nutrition Modelling, Department of Animal and Poultry Science, University of Guelph, ON, Canada
    J Theor Biol 262:361-9. 2010
    ..In conclusion, the regulation of F4e release from Bp by Ins and Leu, and of F2d recycling by uncharged tRNA can be tied together to describe a wide range of FSR values across tissues and physiological states...
  81. ncbi tRNA binding properties of eukaryotic translation initiation factor 2 from Encephalitozoon cuniculi
    Marie Naveau
    Ecole Polytechnique, Laboratoire de Biochimie, F 91128 Palaiseau cedex, France
    Biochemistry 49:8680-8. 2010
    ..These results, together with those previously obtained with archaeal aIF2 and yeast eIF2, show species-specific distributions of the roles of the peripheral subunits of e/aIF2 in tRNA binding...
  82. ncbi Phosphorylation of the alpha-subunit of the eukaryotic initiation factor-2 (eIF2alpha) reduces protein synthesis and enhances apoptosis in response to proteasome inhibition
    Hao Yuan Jiang
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
    J Biol Chem 280:14189-202. 2005
    ..We conclude that eIF2alpha kinases are integral to cellular stress pathways induced by proteasome inhibitors, and may be central to the efficacy of anticancer drugs that target the ubiquitin/proteasome pathway...
  83. ncbi Characteristics of the eukaryotic initiation factor 2 associated 67-kDa polypeptide
    M K Ray
    Department of Chemistry, University of Nebraska, Lincoln 68588
    Biochemistry 32:5151-9. 1993
    ..4) p67:eIF-2 interaction is necessary for p67 activity to protect the eIF-2 alpha-subunit from eIF-2 kinase(s) catalyzed phosphorylation.(ABSTRACT TRUNCATED AT 250 WORDS)..
  84. pmc Identification of domains and residues within the epsilon subunit of eukaryotic translation initiation factor 2B (eIF2Bepsilon) required for guanine nucleotide exchange reveals a novel activation function promoted by eIF2B complex formation
    E Gomez
    Department of Anatomy and Physiology, Medical Sciences Institute, University of Dundee, Dundee, United Kingdom
    Mol Cell Biol 20:3965-76. 2000
    ..This suggests that the N-terminal region of eIF2Bepsilon is an activation domain that responds to eIF2B complex formation...
  85. pmc Parasite-specific eIF2 (eukaryotic initiation factor-2) kinase required for stress-induced translation control
    William J Sullivan
    Department of Pharmacology and Toxicology, Indiana University School of Medicine, 635 Barnhill Drive, Medical Sciences Bldg, Indianapolis, IN 46202, USA
    Biochem J 380:523-31. 2004
    ....
  86. pmc Guanine nucleotide exchange factor for eukaryotic translation initiation factor 2 in Saccharomyces cerevisiae: interactions between the essential subunits GCD2, GCD6, and GCD7 and the regulatory subunit GCN3
    J L Bushman
    Section on Molecular Genetics of Lower Eukaryotes, National Institute of Child Health and Human Development, Bethesda, Maryland 20892
    Mol Cell Biol 13:4618-31. 1993
    ....
  87. pmc The gamma(1)34.5 protein of herpes simplex virus 1 complexes with protein phosphatase 1alpha to dephosphorylate the alpha subunit of the eukaryotic translation initiation factor 2 and preclude the shutoff of protein synthesis by double-stranded RNA-activa
    B He
    Marjorie B Kovler Viral Oncology Laboratories, University of Chicago, IL 60637, USA
    Proc Natl Acad Sci U S A 94:843-8. 1997
    ..The proposed mechanism for maintenance of protein synthesis in the face of double-stranded RNA accumulation is different from that described for viruses examined to date...
  88. pmc Growth arrest and DNA damage-inducible protein GADD34 targets protein phosphatase 1 alpha to the endoplasmic reticulum and promotes dephosphorylation of the alpha subunit of eukaryotic translation initiation factor 2
    Matthew H Brush
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Mol Cell Biol 23:1292-303. 2003
    ..These data provide new insights into the mode of action of GADD34 in assembling an ER-associated eIF-2 alpha phosphatase that regulates protein translation in mammalian cells...
  89. pmc Amino acid microsequencing of internal tryptic peptides of heme-regulated eukaryotic initiation factor 2 alpha subunit kinase: homology to protein kinases
    J J Chen
    Harvard MIT Division of Health Sciences, Cambridge, MA 02139
    Proc Natl Acad Sci U S A 88:315-9. 1991
    ..Since little is known about the function of conserved domain IX, P-74 peptide may be useful in elucidating the role of this domain of protein kinases...
  90. ncbi An inhibitor of elongation factor G (EF-G) GTPase present in the ribosome wash of Escherichia coli: a complex of initiation factors IF1 and IF3?
    K Nagel
    Institut fur Biochemie und Lebensmittelchemie, Universitat Hamburg, Germany
    Biochim Biophys Acta 1129:145-8. 1992
    ..Therefore, IF1 as well as the EF-G GTPase inhibitor do not influence the ribosome-dependent EF-G GTPase by affecting the association of ribosomal subunits...
  91. ncbi Nck in a complex containing the catalytic subunit of protein phosphatase 1 regulates eukaryotic initiation factor 2alpha signaling and cell survival to endoplasmic reticulum stress
    Mathieu Latreille
    Polypeptide Hormone Laboratory, Department of Medicine, McGill University, Montreal, Quebec H3A 2B2, Canada
    J Biol Chem 281:26633-44. 2006
    ..In this manner, Nck modulates translation and eIF2alpha signaling in response to ER stress...
  92. ncbi Glycogen synthase kinase 3beta (GSK3beta) mediates 6-hydroxydopamine-induced neuronal death
    Gang Chen
    Department of Microbiology, Immunology and Cell Biology, West Virginia University School of Medicine, Robert C Byrd Health Sciences Center, Morgantown, West Virginia 26506, USA
    FASEB J 18:1162-4. 2004
    ..These results suggest that GSK3beta is a critical intermediate in pro-apoptotic signaling cascades that are associated with neurodegenerative diseases, thus providing a potential target site amenable to pharmacological intervention...
  93. ncbi Chromium alleviates glucose intolerance, insulin resistance, and hepatic ER stress in obese mice
    Nair Sreejayan
    Division of Pharmaceutical Sciences and Center for Cardiovascular Research and Alternative Medicine, School of Pharmacy, University of Wyoming, Laramie, Wyoming, USA
    Obesity (Silver Spring) 16:1331-7. 2008
    ..The study tested the hypothesis that Cr(D-phe)(3) suppresses endoplasmic reticulum (ER) stress and insulin resistance in these animals...
  94. ncbi Nutritional stimulation of milk protein yield of cows is associated with changes in phosphorylation of mammary eukaryotic initiation factor 2 and ribosomal s6 kinase 1
    Chanelle A Toerien
    Department of Animal and Poultry Science and 5Department of Clinical Studies, University of Guelph, Ontario, N1G 2W1 Canada
    J Nutr 140:285-92. 2010
    ....
  95. ncbi Alternative mechanisms of initiating translation of mammalian mRNAs
    R J Jackson
    Department of Biochemistry, 80 Tennis Court Road, University of Cambridge, Cambridge CB2 1GA, UK
    Biochem Soc Trans 33:1231-41. 2005
    ....
  96. ncbi Platelet-derived growth factor signal transduction through the interferon-inducible kinase PKR. Immediate early gene induction
    L J Mundschau
    Cancer Research Center, Boston University School of Medicine, Massachusetts 02118
    J Biol Chem 270:3100-6. 1995
    ..These results provide direct evidence that PKR activation functions as a second messenger in a growth factor signal transduction pathway. Thus, PKR may serve as a common mediator of growth-promoting and growth inhibitory signals...
  97. pmc Minimum requirements for the function of eukaryotic translation initiation factor 2
    F L Erickson
    Department of Molecular and Cell Biology, University of Texas at Dallas, Richardson, TX 75083 0688, USA
    Genetics 158:123-32. 2001
    ..GTP.Met-tRNA(i)(Met) ternary complexes in vivo...
  98. pmc Cloning and expression of cDNAs for the beta subunit of eukaryotic initiation factor-2B, the guanine nucleotide exchange factor for eukaryotic initiation factor-2
    B L Craddock
    Department of Biochemistry, School of Medical Sciences, University of Bristol U K
    Biochem J 309:1009-14. 1995
    ..Northern-blot analysis revealed a single major mRNA species for eIF-2B beta in each of the four rabbit tissues tested...
  99. pmc The eIF2 kinase GCN2 is essential for the murine immune system to adapt to amino acid deprivation by asparaginase
    Piyawan Bunpo
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine Evansville, Evansville, IN 47712, USA
    J Nutr 140:2020-7. 2010
    ..05). These results indicate that loss of GCN2 enhances immunosuppression by ASNase and that this eIF2 kinase is broadly required for amino acid stress management in the immune system...
  100. ncbi Differential regulation of the endoplasmic reticulum stress response in pancreatic beta-cells exposed to long-chain saturated and monounsaturated fatty acids
    Eleftheria Diakogiannaki
    Peninsula Medical School, Institute of Biomedical and Clinical Science, John Bull Building, Plymouth PL6 8BU, UK
    J Endocrinol 197:553-63. 2008
    ..This effect is antagonised by monounsaturates that may exert their anti-apoptotic actions by regulating the activity of one or more kinase enzymes involved in mediating the phosphorylation of eIF2 alpha...
  101. pmc Cloning of cDNA for the gamma-subunit of mammalian translation initiation factor 2B, the guanine nucleotide-exchange factor for eukaryotic initiation factor 2
    N T Price
    Department of Biochemistry, University of Bristol, U K
    Biochem J 318:631-6. 1996
    ..The roles of these motifs are discussed in relation to the known properties of eIF2B...

Research Grants61

  1. TRANSLATIONAL CONTROL IN REGULATION OF APOPTOSIS
    Randal Kaufman; Fiscal Year: 2002
    ....
  2. The Unfolded Protein Response After Brain Ischemia
    DONALD DEGRACIA; Fiscal Year: 2006
    ..abstract_text> ..
  3. Regulation of ER stress-induced cell death
    Randal J Kaufman; Fiscal Year: 2013
    ..The proposed studies on protein synthesis will provide vital information that should encourage the development of novel therapeutics to treat diabetes. ..
  4. UV-induced and NOS-mediated Zn elevation, translation regulation and apoptosis
    Shiyong Wu; Fiscal Year: 2012
    ..The outcomes from these studies will not only increase our knowledge of UV- induced multiple apoptotic signaling pathways, but will also lead us to the development of new therapeutics for treatment of UV-related skin aging and cancers. ..
  5. INTERFERON GAMMA EFFECTS ON OLIGODENDROCYTES
    BRIAN J POPKO; Fiscal Year: 2012
    ..The studies described in the current proposal are designed to further characterize this potentially important clinical target in immune-mediated demyelinating disorders. ..
  6. Cross-talk between GCN2 and mTOR in integration of nutrient signaling
    MARTHA STIPANUK; Fiscal Year: 2009
    ..abstract_text> ..
  7. Translational control and latent Toxoplasma infection
    RONALD C contact WEK; Fiscal Year: 2010
    ..The regulation of gene expression plays a key role in this pathogenic process;therefore, our results will be important for new therapies to combat opportunistic infectious diseases, such as Toxoplasma. ..
  8. Targeting Endoplasmic Reticulum Stress Response for Cancer Therapy
    Bertal H Aktas; Fiscal Year: 2013
    ....
  9. Cigarette Smoke, RIG-like Helicases and Alveolar Remodeling
    Jack A Elias; Fiscal Year: 2012
    ..4. Define the mechanism by which RLH-mediated innate activation regulates progenitor cell based repair responses in mice exposed to CS plus virus/viral PAMPs. ..
  10. GENE AMPLIFICATION BY A TRANSPOSITION APPARATUS
    Hiroshi Nakai; Fiscal Year: 2010
    ..This work will further define the cellular apparatus that maintains the stability and integrity of the genome, preventing genetic alterations associated with cellular dysfunction. ..
  11. Regulators of Osteoblast Protein Synthesis Initiation
    THOMAS LEO MCCARTHY; Fiscal Year: 2013
    ....
  12. Stress responses in the AIDS opportunistic parasite Toxoplasma gondii
    BRAD JOYCE; Fiscal Year: 2012
    ..The type II TgIF21-S71A will establish the role of stress-induced TgIF21 phosphorylation on Toxoplasma development and cyst latency. ..
  13. The structural dynamics of translation initiation
    Ruben L Gonzalez; Fiscal Year: 2013
    ....
  14. Inhibition of phosphatase activity as a novel treatment for chronic toxoplasmosis
    Ronald C Wek; Fiscal Year: 2013
    ....
  15. Protein Kinase B and C in Head Injury
    Larry Jenkins; Fiscal Year: 2007
    ....
  16. MECHANISMS & REGULATION OF PROTEIN SYNTHESIS
    ALBERT WAHBA; Fiscal Year: 1992
    ..The isolated clones will be characterized by restriction mapping, nucleotide sequencing, and their derived amino acid sequence. The sequencing of the genomic clones for ..
  17. TRANSLATIONAL CONTROL OF PROTEIN SYNTHESIS BY HEMIN
    Martin Gross; Fiscal Year: 1990
    ..5M K C1-washed ribosomes is insensitive to inhibition oby phosphorylation of eIF-2Alpha and whether this may be related to RF-mediated dissociation of eIF-2 GDP from 60S subunits...
  18. PROTEIN SYNTHESIS INITIATION IN YEAST (S. CEREVISIAE)
    NABA GUPTA; Fiscal Year: 1993
    ....
  19. UV-induced and NOS-mediated Zn elevation, translation regulatin and apoptosis.
    Shiyong Wu; Fiscal Year: 2007
    ..g., reperfusion, wound healing, diabetes) that are affected by NO and translation inhibition. ..
  20. Gene expression and the eIF2 Kinase stress response
    Krishna Vattem; Fiscal Year: 2005
    ..Together these studies will be important for understanding the molecular mechanisms regulating gene specific translation in higher eukaryotes during adaptive responses to environmental stresses. ..
  21. Alcohol-Induced Regulation of Hepatic Protein Synthesis
    THOMAS VARY; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  22. REGULATION OF MAMMALIAN PROTEIN SYNTHESIS
    John Ludlow; Fiscal Year: 1993
    ..It is proposed to purify and characterize this factor. Characterization of the factor will indicate whether there is a mechanism regulating protein synthesis which is based upon calmodulin...
  23. SUPPRESSION OF PROTEIN SYNTHESIS IN REPERFUSED BRAIN
    Gary Krause; Fiscal Year: 2003
    ..abstract_text> ..
  24. HERPES SIMPLEX VIRUS INFECTION AND CELLULAR RESPONSE
    Bin He; Fiscal Year: 2004
    ..5 protein can be functionally substituted by the corresponding homologous domain of the cellular protein GADD34/MyD116, these studies may also shed light on cell growth control. ..
  25. Cell Survival in Brain Reperfusion
    Jonathon Sullivan; Fiscal Year: 2004
    ..This approach will permit integrated examination of a signaling system that may link growth factor mediated survival and translational competence in the setting of brain reperfusion. ..
  26. PROTEIN SYNTHESIS INITIATION IN ANIMAL CELLS
    Bansidhar Datta; Fiscal Year: 2002
    ..This research is expected to provide valuable information regarding the mechanism of protein synthesis initiation in normal, cancerous, and virus- infected animal cells. ..
  27. GCN5-mediated transcription in AIDS pathogen Toxoplasma
    WILLIAM SULLIVAN JR; Fiscal Year: 2008
    ..Thus, our results will fundamentally advance the fields of parasitology and eukaryotic gene expression. ..
  28. APEs as novel drug targets in AIDS opportunistic pathogen Toxoplasma
    WILLIAM SULLIVAN JR; Fiscal Year: 2008
    ..Moreover, Toxoplasma can be informative as a model organism to study Plasmodium, the causative agent of malaria. [unreadable] [unreadable] [unreadable] [unreadable]..
  29. GCN5-mediated transcription in AIDS pathogen Toxoplasma
    WILLIAM SULLIVAN JR; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  30. REGULATION OF PROTEIN SYNTHESIS AND ERYTHROPOIESIS
    Jane Jane Chen; Fiscal Year: 2007
    ..HRI is also important for the survival of mice with thalassemia and erythropoietic protoporphria. Our proposed study may lead to potential application of HRI in treating human patients with red cell diseases. ..
  31. INTEGRATIVE RESPONSES TO AMINO ACID DEFICIENCY
    Dorothy Gietzen; Fiscal Year: 2004
    ....
  32. Characterization of mammalian stress granules
    Paul J Anderson; Fiscal Year: 2010
    ..These studies have implications for our understanding of stress-regulated pathological conditions, including Alzheimer's disease, diabetes and cancer. ..
  33. TRANSGENIC ANIMAL MODEL DEVELOPMENT--PKR PROTEIN KINASE
    Warren Ladiges; Fiscal Year: 2001
    ..abstract_text> ..
  34. Promotion of PDT Induced phototoxicity by bile acids
    David Kessel; Fiscal Year: 2003
    ..If the results of preliminary studies are borne out by further investigation, UDCA could offer a safe and effective means for promoting clinical PDT efficacy. ..
  35. REGULATION OF PROTEIN TURNOVER IN SEPSIS
    Scot R Kimball; Fiscal Year: 2010
    ....
  36. ROLE OF PSGL 1 IN NATURAL KILLER CELL FUNCTION
    Paul Anderson; Fiscal Year: 2003
    ..Consequently, the overall goal of the proposed experiments is to determine how PEN5:L-selectin interactions influence NK cell function. ..
  37. Conformational Diseases of the Secretory Pathway
    Randal Kaufman; Fiscal Year: 2003
    ..This conference will focus on new technologies and methodologies to study this rapidly moving field in order to dissect the complexity and diversity of ER function. ..
  38. DNA FORMS OF MURINE LEUKEMIA VIRUSES
    FAYTH YOSHIMURA; Fiscal Year: 2007
    ..The results of these studies will enhance our understanding of the role of apoptosis in the development of neoplastic disease. ..
  39. MECHANISMS AND SIGNIFICANCE OF HYPOXIA INDUCED G1 ARREST
    Lawrence Gardner; Fiscal Year: 2006
    ..abstract_text> ..
  40. Conference on Photodynamic Therapy
    David Kessel; Fiscal Year: 2002
    ..The most recent PDT meeting, sponsored by the International Photodynamic Assn, has more than 600 participants. ..
  41. ESSENTIAL AMINO ACIDS AND SEIZURE SUSCEPTIBILITY
    Dorothy Gietzen; Fiscal Year: 2001
    ..And finally it is hoped that the seizures in a whole animal can be blocked by blocking the relevant neurotransmitter systems. ..
  42. VIRULENCE FACTORS OF GROUP B STREPTOCOCCI
    John Bohnsack; Fiscal Year: 2001
    ..This approach will ultimately contribute to understanding the molecular basis of disease caused by GBS, and help devise strategies for preventing and treating this important cause of serious human neonatal bacterial infection. ..
  43. STRUCTURE/FUNCTION OF HEME REGULATED ELF-2ALPHA KINASE
    Jane Jane Chen; Fiscal Year: 2001
    ..Structure-function analysis of HRI will advance our knowledge not only on the regulation of protein kinases which are vital in the regulation of various cellular processes, but also on the regulation of heme proteins. ..
  44. REGULATION OF PROTEIN SYNTHESIS AND ERYTHROPOIESIS
    Jane Jane Chen; Fiscal Year: 2008
    ..The small chemicals discovered in this proposed research might also have great potential in helping to treat drug-resistant cancer cells. ..
  45. High Throughput Chemical Genomics to Identify Novel Inhibitors of CHOP
    Randal Kaufman; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  46. Post-transcriptional regulation of TNF-alpha production
    Paul Anderson; Fiscal Year: 2005
    ..These studies might also identify molecular targets for the development of orally available TNFa blockers that can be used to treat patients with rheumatoid arthritis. ..
  47. Alzheimer's Disease and Impaired APP Proteolysis
    Warren Ladiges; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  48. RESEARCH TRAINING IN PHYSIOLOGICAL ADAPTATION TO STRESS
    Leonard Jefferson; Fiscal Year: 2005
    ..abstract_text> ..
  49. Unfolded Protein Response in Glucose Homeostasis
    Randal Kaufman; Fiscal Year: 2006
    ..These in vivo models have the potential for providing novel biologic insights into human disease and may also facilitate testing of new therapies. [unreadable] [unreadable] [unreadable]..
  50. Comparative Mouse Genomics Center
    Warren Ladiges; Fiscal Year: 2006
    ....
  51. IMMUNOBIOLOGY OF AGING IN GENETICALLY ALTERED MICE
    Warren Ladiges; Fiscal Year: 2004
    ....
  52. Innate immune evasion and/or antagonism by eastern equine encephalitis virus
    KATHERINE RYMAN; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  53. Control of TGF-beta Activity in Bone
    Michael Centrella; Fiscal Year: 2007
    ..Due to the importance of TGF-beta in bone metabolism, studies like these that initiate with TbetaR expression on osteoblasts may continue to define new molecular targets that could be used to focus and enhance bone growth and repair. ..
  54. Control of lymphomagenesis by ATM through ROS, mTOR and PP2A signaling
    Mingshan Yan; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  55. Unfolded proteins in the Endoplasmic Reticulum to Disease
    Randal Kaufman; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  56. p38 MAP Kinase and Akt Interaction in HUVEC
    Shehla Pervin; Fiscal Year: 2008
    ..This investigation could help us understand the mechanisms by which the mortality rate of male fetus and neonates is higher than female. [unreadable] [unreadable] [unreadable]..
  57. Radiosensitization with the HIV protease inhibior Nelfinavir in NSCLC
    Anjali Gupta; Fiscal Year: 2008
    ..Specific Aim 3. To investigate in vitro the molecular mechanisms by which NFV results in sensitization. [unreadable] [unreadable] [unreadable]..
  58. The role of FAST in immune-mediated inflammatory disease
    Paul Anderson; Fiscal Year: 2008
    ..Finally, we will generate transgenic mice that overexpress FAST and mutant mice that lack FAST to determine its importance in the initiation and/or propagation of immune-mediated inflammatory disease. ..
  59. Age and Sleep Effects on ER Protein Function
    Nirinjini Naidoo; Fiscal Year: 2005
    ..We will use 2-D DIGE, as well as oxidation assays and mass spectrometry, to identify proteins that are altered by aging and sleep deprivation in the ER. ..
  60. Translational Control by elF2 Kinase during ER Stress
    RONALD WEK; Fiscal Year: 2008
    ..Together, addressing these aims will increase our understanding of the process of cellular adaptation to environmental stresses and its impact in human disease. [unreadable] [unreadable]..
  61. Brain Signaling of Essential Amino Acid Deficiency
    Dorothy Gietzen; Fiscal Year: 2006
    ..When APC neurons are activated, their glutamatergic output first acts at AMPA receptors to signal AA deficiency to other parts of the brain for the anorectic responses. ..