eif 2 kinase

Summary

Summary: A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. In the presence of dsRNA and ATP, the kinase autophosphorylates on several serine and threonine residues. The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis.

Top Publications

  1. ncbi Regulated translation initiation controls stress-induced gene expression in mammalian cells
    H P Harding
    Skirball Institute of Biomolecular Medicine The Department of Medicine, Kaplan Cancer Center New York University School of Medicine, New York, NY 10016, USA
    Mol Cell 6:1099-108. 2000
  2. ncbi Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase
    H P Harding
    Skirball Institute of Biomolecular Medicine, Department of Medicine, NYU School of Medicine, New York 10016, USA
    Nature 397:271-4. 1999
  3. ncbi Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response
    A Bertolotti
    Skirball Institute of Biomolecular Medicine, Departments of Medicine and Cell Biology and the Kaplan Cancer Center, New York University School of Medicine, New York, New York 10016, USA
    Nat Cell Biol 2:326-32. 2000
  4. pmc Feedback inhibition of the unfolded protein response by GADD34-mediated dephosphorylation of eIF2alpha
    I Novoa
    Skirball Institute of Biomolecular Medicine, Department of Medicine, New York University School of Medicine, New York, NY 10016, USA
    J Cell Biol 153:1011-22. 2001
  5. ncbi Perk is essential for translational regulation and cell survival during the unfolded protein response
    H P Harding
    Department of Medicine, The Kaplan Cancer Center, New York University School of Medicine, New York 10016, USA
    Mol Cell 5:897-904. 2000
  6. pmc Impact of protein kinase PKR in cell biology: from antiviral to antiproliferative action
    M A Garcia
    Department of Molecular and Cellular Biology, Centro Nacional de Biotecnologia, Ciudad Universitaria Cantoblanco, 28049 Madrid, Spain
    Microbiol Mol Biol Rev 70:1032-60. 2006
  7. ncbi Cell death and endoplasmic reticulum stress: disease relevance and therapeutic opportunities
    InKi Kim
    Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, California 92037, USA
    Nat Rev Drug Discov 7:1013-30. 2008
  8. ncbi EIF2AK3, encoding translation initiation factor 2-alpha kinase 3, is mutated in patients with Wolcott-Rallison syndrome
    M Delepine
    Centre National de Genotypage, Evry, France
    Nat Genet 25:406-9. 2000
  9. pmc ER stress-regulated translation increases tolerance to extreme hypoxia and promotes tumor growth
    Meixia Bi
    Department of Radiation Oncology, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA
    EMBO J 24:3470-81. 2005
  10. ncbi Proapoptotic BAX and BAK modulate the unfolded protein response by a direct interaction with IRE1alpha
    Claudio Hetz
    Howard Hughes Medical Institute, Dana Farber Cancer Institute, and Harvard Medical School, Boston, MA 02115, USA
    Science 312:572-6. 2006

Research Grants

Detail Information

Publications221 found, 100 shown here

  1. ncbi Regulated translation initiation controls stress-induced gene expression in mammalian cells
    H P Harding
    Skirball Institute of Biomolecular Medicine The Department of Medicine, Kaplan Cancer Center New York University School of Medicine, New York, NY 10016, USA
    Mol Cell 6:1099-108. 2000
    ..Mammalian cells thus utilize an ancient pathway to regulate gene expression in response to diverse stress signals...
  2. ncbi Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase
    H P Harding
    Skirball Institute of Biomolecular Medicine, Department of Medicine, NYU School of Medicine, New York 10016, USA
    Nature 397:271-4. 1999
    ..These properties implicate PERK in a signalling pathway that attenuates protein translation in response to ER stress...
  3. ncbi Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response
    A Bertolotti
    Skirball Institute of Biomolecular Medicine, Departments of Medicine and Cell Biology and the Kaplan Cancer Center, New York University School of Medicine, New York, New York 10016, USA
    Nat Cell Biol 2:326-32. 2000
    ..These findings are consistent with a model in which BiP represses signalling through PERK and IRE1 and protein misfolding relieves this repression by effecting the release of BiP from the PERK and IRE1 lumenal domains...
  4. pmc Feedback inhibition of the unfolded protein response by GADD34-mediated dephosphorylation of eIF2alpha
    I Novoa
    Skirball Institute of Biomolecular Medicine, Department of Medicine, New York University School of Medicine, New York, NY 10016, USA
    J Cell Biol 153:1011-22. 2001
    ....
  5. ncbi Perk is essential for translational regulation and cell survival during the unfolded protein response
    H P Harding
    Department of Medicine, The Kaplan Cancer Center, New York University School of Medicine, New York 10016, USA
    Mol Cell 5:897-904. 2000
    ..PERK thus plays a major role in the ability of cells to adapt to ER stress...
  6. pmc Impact of protein kinase PKR in cell biology: from antiviral to antiproliferative action
    M A Garcia
    Department of Molecular and Cellular Biology, Centro Nacional de Biotecnologia, Ciudad Universitaria Cantoblanco, 28049 Madrid, Spain
    Microbiol Mol Biol Rev 70:1032-60. 2006
    ..The case for the pathological consequences of the antiproliferative action of PKR is less understood, but therapeutic strategies aimed at targeting PKR are beginning to offer promising results...
  7. ncbi Cell death and endoplasmic reticulum stress: disease relevance and therapeutic opportunities
    InKi Kim
    Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, California 92037, USA
    Nat Rev Drug Discov 7:1013-30. 2008
    ....
  8. ncbi EIF2AK3, encoding translation initiation factor 2-alpha kinase 3, is mutated in patients with Wolcott-Rallison syndrome
    M Delepine
    Centre National de Genotypage, Evry, France
    Nat Genet 25:406-9. 2000
    ..Our results provide evidence for the role of EIF2AK3 in WRS. The identification of this gene may provide insight into the understanding of the more common forms of diabetes and other pathologic manifestations of WRS...
  9. pmc ER stress-regulated translation increases tolerance to extreme hypoxia and promotes tumor growth
    Meixia Bi
    Department of Radiation Oncology, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA
    EMBO J 24:3470-81. 2005
    ..Collectively, these findings demonstrate that activation of the ISR is required for tumor cell adaptation to hypoxia, and suggest that this pathway is an attractive target for antitumor modalities...
  10. ncbi Proapoptotic BAX and BAK modulate the unfolded protein response by a direct interaction with IRE1alpha
    Claudio Hetz
    Howard Hughes Medical Institute, Dana Farber Cancer Institute, and Harvard Medical School, Boston, MA 02115, USA
    Science 312:572-6. 2006
    ..Thus, BAX and BAK function at the ER membrane to activate IRE1alpha signaling and to provide a physical link between members of the core apoptotic pathway and the UPR...
  11. ncbi Viruses, endoplasmic reticulum stress, and interferon responses
    B He
    Department of Microbiology and Immunology, College of Medicine, The University of Illinois at Chicago, 835 South Wolcott Avenue, Chicago, IL 60612, USA
    Cell Death Differ 13:393-403. 2006
    ..This review highlights recent progress in these areas...
  12. pmc Functional coupling of p38-induced up-regulation of BiP and activation of RNA-dependent protein kinase-like endoplasmic reticulum kinase to drug resistance of dormant carcinoma cells
    Aparna C Ranganathan
    Department of Biomedical Sciences, School of Public Health and Center for Excellence in Cancer Genomics, University at Albany, State University of New York, Rensselaer, NY 12144, USA
    Cancer Res 66:1702-11. 2006
    ..We propose that stress-dependent activation of p38 via BiP up-regulation and PERK activation protects dormant tumor cells from stress insults, such as chemotherapy...
  13. pmc The crystal structure of human IRE1 luminal domain reveals a conserved dimerization interface required for activation of the unfolded protein response
    Jiahai Zhou
    Life Sciences Institute, LSI 3163B, Department of Biological Chemistry, University of Michigan Medical Center, 210 Washtenaw Avenue, Ann Arbor, MI 48109, USA
    Proc Natl Acad Sci U S A 103:14343-8. 2006
    ..Our structural, biochemical, and functional studies in vivo altogether demonstrate that IRE1 and PERK have conserved a common molecular interface necessary and sufficient for dimerization and UPR signaling...
  14. ncbi Host defense, viruses and apoptosis
    G N Barber
    Department of Microbiology and Immunology and Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, FL 33136, USA
    Cell Death Differ 8:113-26. 2001
    ..This likelihood is additionally underlined by the elaborate strategies developed by viruses to inhibit IFN-antiviral function and the mechanisms of cell death...
  15. ncbi Induction of Grp78/BiP by translational block: activation of the Grp78 promoter by ATF4 through and upstream ATF/CRE site independent of the endoplasmic reticulum stress elements
    Shengzhan Luo
    Department of Biochemistry and Molecular Biology, University of Southern California Keck School of Medicine, Los Angeles, California 90089 9176, USA
    J Biol Chem 278:37375-85. 2003
    ..Our studies resolve a mechanism responsible for inhibition of Grp78 mRNA induction by ER stress in cells that are functionally null for PERK or devoid of eIF2alpha phosphorylation...
  16. ncbi Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1
    F Urano
    Skirball Institute of Biomolecular Medicine, Departments of Medicine, Cell Biology and the Kaplan Cancer Center, New York University Medical School, New York, NY 10016, USA
    Science 287:664-6. 2000
    ..Dominant-negative TRAF2 inhibited activation of JNK by IRE1. Activation of JNK by endogenous signals initiated in the ER proceeds by a pathway similar to that initiated by cell surface receptors in response to extracellular signals...
  17. ncbi Diabetes mellitus and exocrine pancreatic dysfunction in perk-/- mice reveals a role for translational control in secretory cell survival
    H P Harding
    Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 10016, New York, NY, USA
    Mol Cell 7:1153-63. 2001
    ..These findings suggest a special role for translational control in protecting secretory cells from ER stress...
  18. ncbi The protein kinase PKR is required for macrophage apoptosis after activation of Toll-like receptor 4
    Li Chung Hsu
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093 0636, USA
    Nature 428:341-5. 2004
    ..The pro-apoptotic actions of PKR are mediated both through inhibition of protein synthesis and activation of interferon response factor 3...
  19. ncbi RAX, a cellular activator for double-stranded RNA-dependent protein kinase during stress signaling
    T Ito
    Sealy Center for Oncology and Hematology, Department of Internal Medicine, The University of Texas Medical Branch at Galveston, Galveston Texas 77555 1048, USA
    J Biol Chem 274:15427-32. 1999
    ..Therefore, cellular RAX may be a stress-activated, physiologic activator of PKR that couples transmembrane stress signals and protein synthesis...
  20. pmc Stress-induced gene expression requires programmed recovery from translational repression
    Isabel Novoa
    Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA
    EMBO J 22:1180-7. 2003
    ....
  21. ncbi Signal integration via PKR
    B R Williams
    The author is in the Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    Sci STKE 2001:re2. 2001
    ..Although the conflicts may not be resolved in this review, suggestions are made for experiments that could lead to a clearer understanding of the mechanisms involved...
  22. ncbi eIF2 and the control of cell physiology
    Christopher G Proud
    Division of Molecular Physiology, School of Life Sciences, University of Dundee, Dunde DD15EH, United Kingdom
    Semin Cell Dev Biol 16:3-12. 2005
    ....
  23. pmc The protein kinase PKR is required for p38 MAPK activation and the innate immune response to bacterial endotoxin
    K C Goh
    Department of Cancer Biology NB40, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    EMBO J 19:4292-7. 2000
    ..Our findings indicate, for the first time, that PKR is required for p38 MAPK signaling and plays a potentially important role in the innate response against bacterial endotoxin...
  24. pmc PACT, a protein activator of the interferon-induced protein kinase, PKR
    R C Patel
    Department of Molecular Biology, The Lerner Research Institute, The Cleveland Clinic Foundation, OH 44195, USA
    EMBO J 17:4379-90. 1998
    ..In mammalian cells, overexpression of PACT caused PKR activation and, in yeast, co-expression of PACT enhanced the anti-growth effect of PKR. Thus, PACT has the hallmarks of a direct activator of PKR...
  25. pmc IRE1 signaling affects cell fate during the unfolded protein response
    Jonathan H Lin
    Howard Hughes Medical Institute, University of California at San Francisco, San Francisco, CA 94158, USA
    Science 318:944-9. 2007
    ..Key findings from our studies in cell culture were recapitulated in photoreceptors expressing mutant rhodopsin in animal models of retinitis pigmentosa...
  26. ncbi PKR; a sentinel kinase for cellular stress
    B R Williams
    Department of Cancer Biology NB40, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio, OH 44195, USA
    Oncogene 18:6112-20. 1999
    ....
  27. pmc PERK (eIF2alpha kinase) is required to activate the stress-activated MAPKs and induce the expression of immediate-early genes upon disruption of ER calcium homoeostasis
    Shun Hsin Liang
    Department of Biology, The Pennsylvania State University, University Park, PA 16802, USA
    Biochem J 393:201-9. 2006
    ..We suggest that this specificity of PERK function in the UPR is an extension of the normal physiological function of PERK to act as a calcium sensor in the ER...
  28. ncbi The dsRNA protein kinase PKR: virus and cell control
    M A Garcia
    Department of Molecular and Cellular Biology, Centro Nacional de Biotecnologia, CSIC, Ciudad Universitaria Cantoblanco, 28049 Madrid, Spain
    Biochimie 89:799-811. 2007
    ..As a consequence of the effects of PKR on translation, transcription and apoptosis, PKR can function to control cell growth and cell differentiation, and its activity can be controlled by the action of several oncogenes...
  29. pmc Translational control in the endoplasmic reticulum stress response
    David Ron
    Skirball Institute of Biomolecular Medicine, Department of Medicine, New York, New York 10016, USA
    J Clin Invest 110:1383-8. 2002
  30. pmc TRBP control of PACT-induced phosphorylation of protein kinase R is reversed by stress
    Aïcha Daher
    Virus Cell Interactions Laboratory, Lady Davis Institute for Medical Research, Montreal, Quebec, Canada
    Mol Cell Biol 29:254-65. 2009
    ..Our results demonstrate that in cells, TRBP controls PACT activation of PKR, an activity that is reversed by stress...
  31. ncbi Specific recognition of HIV TAR RNA by the dsRNA binding domains (dsRBD1-dsRBD2) of PKR
    Insil Kim
    Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305 5126, USA
    J Mol Biol 358:430-42. 2006
    ..The results presented here provide the biophysical and spectroscopic basis for high-resolution structural studies, and show how local RNA structural features modulate recognition by dsRBDs...
  32. pmc Double-stranded-RNA-dependent protein kinase and TAR RNA-binding protein form homo- and heterodimers in vivo
    G P Cosentino
    Department of Biochemistry, McGill University, Montreal, QC Canada
    Proc Natl Acad Sci U S A 92:9445-9. 1995
    ..Taken together, these results suggest that complexes consisting of different combinations of dsRNA-binding proteins may exist in vivo. Such complexes could mediate differential effects on gene expression and control of cell growth...
  33. pmc NF-kappaB activation by double-stranded-RNA-activated protein kinase (PKR) is mediated through NF-kappaB-inducing kinase and IkappaB kinase
    M Zamanian-Daryoush
    Department of Cancer Biology, The Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    Mol Cell Biol 20:1278-90. 2000
    ..Taken together, these results demonstrate that PKR-dependent dsRNA induction of NF-kappaB is mediated by NIK and IKK activation...
  34. ncbi Intracellular signaling from the endoplasmic reticulum to the nucleus: the unfolded protein response in yeast and mammals
    C Patil
    Howard Hughes Medical Institute, Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, CA 94143, USA
    Curr Opin Cell Biol 13:349-55. 2001
    ..Recent results reveal that the output of the mammalian UPR reaches beyond transcriptional regulation of secretory pathway components to control of general translation, the cell cycle and programmed cell death...
  35. ncbi The eIF-2 alpha protein kinases, regulators of translation in eukaryotes from yeasts to humans
    C E Samuel
    Department of Biological Sciences, University of California, Santa Barbara 93106
    J Biol Chem 268:7603-6. 1993
  36. pmc Structure of the double-stranded RNA-binding domain of the protein kinase PKR reveals the molecular basis of its dsRNA-mediated activation
    S Nanduri
    Structural Biology Program, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    EMBO J 17:5458-65. 1998
    ..The central linker is highly flexible, which may enable the two dsRBMs to wrap around the RNA duplex for cooperative and high-affinity binding, leading to the overall change of PKR conformation and its activation...
  37. pmc PERK-dependent regulation of lipogenesis during mouse mammary gland development and adipocyte differentiation
    Ekaterina Bobrovnikova-Marjon
    The Leonard and Madlyn Abramson Family Cancer Research Institute and Cancer Center, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 105:16314-9. 2008
    ..These findings implicate PERK as a physiologically relevant regulator of the lipogenic pathway...
  38. pmc Cigarette smoke selectively enhances viral PAMP- and virus-induced pulmonary innate immune and remodeling responses in mice
    Min Jong Kang
    Section of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA
    J Clin Invest 118:2771-84. 2008
    ..These studies demonstrate that CS selectively augments the airway and alveolar inflammatory and remodeling responses induced in the murine lung by viral PAMPs and viruses...
  39. ncbi Loss of kinase activity in a patient with Wolcott-Rallison syndrome caused by a novel mutation in the EIF2AK3 gene
    Anna Biason-Lauber
    University Children s Hospital, Division of Pediatric Endocrinology Diabetology, Steinwiesstrasse 75, 8032 Zurich, Switzerland
    Diabetes 51:2301-5. 2002
    ..Our data demonstrate that EIF2AK3 kinase activity is essential for pancreas islet function and bone development in humans, and we suggest EIF2AK3 as a possible target for therapeutic intervention in diabetes...
  40. ncbi The double-stranded RNA activated protein kinase PKR physically associates with the tumor suppressor p53 protein and phosphorylates human p53 on serine 392 in vitro
    A R Cuddihy
    Department of Oncology, McGill University, Montreal, Quebec, Canada
    Oncogene 18:2690-702. 1999
    ....
  41. ncbi Dimerization and release of molecular chaperone inhibition facilitate activation of eukaryotic initiation factor-2 kinase in response to endoplasmic reticulum stress
    Kun Ma
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
    J Biol Chem 277:18728-35. 2002
    ....
  42. ncbi The binding selectivity of ADAR2's dsRBMs contributes to RNA-editing selectivity
    Olen M Stephens
    Department of Chemistry, University of Utah, Salt Lake City, UT 84112, USA
    Chem Biol 11:1239-50. 2004
    ..In addition, the editing activity of a mutant of ADAR2 lacking dsRBM I on N(2)-benzylguanosine-modified RNA suggests the location of the dsRBM I binding site that leads to editing at the GluR-B Q/R site...
  43. pmc PERK and GCN2 contribute to eIF2alpha phosphorylation and cell cycle arrest after activation of the unfolded protein response pathway
    Robert B Hamanaka
    The Leonard and Madlyn Abramson Family Cancer Research Institute and Cancer Center, Department of Cancer Biology, University of Pennsylvania Cancer Center, Philadelphia, PA 19104, USA
    Mol Biol Cell 16:5493-501. 2005
    ..Our results demonstrate that PERK and GCN2 function to cooperatively regulate eIF2alpha phosphorylation and cyclin D1 translation after UPR activation...
  44. ncbi The double-strand RNA-dependent protein kinase PKR plays a significant role in a sustained ER stress-induced apoptosis
    Eun Soo Lee
    Department of Biological Science, Sungkyunkwan University, Cheoncheon Dong 300, Jangan gu, Suwon, Gyeonggi do 440 746, South Korea
    FEBS Lett 581:4325-32. 2007
    ..These results indicate that the ER-stress-mediated eIF2alpha/ATF4/CHOP/cell death pathway is, to some degree, dependent on PACT-mediated PKR activation apart from the PERK pathway...
  45. pmc Activating transcription factor 4 is translationally regulated by hypoxic stress
    Jaime D Blais
    Ottawa Regional Cancer Center, Ontario, Canada
    Mol Cell Biol 24:7469-82. 2004
    ..Taken with the concomitant induction of additional ER-resident proteins identified by our microarray analysis, this study suggests an important integrated response between ER signaling and the cellular adaptation to hypoxic stress...
  46. pmc The PERK eukaryotic initiation factor 2 alpha kinase is required for the development of the skeletal system, postnatal growth, and the function and viability of the pancreas
    Peichuan Zhang
    Department of Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA
    Mol Cell Biol 22:3864-74. 2002
    ..The skeletal, pancreatic, and growth defects are similar to those seen in human Wolcott-Rallison syndrome...
  47. ncbi Double-stranded RNA-dependent protein kinase phosphorylation of the alpha-subunit of eukaryotic translation initiation factor 2 mediates apoptosis
    Donalyn Scheuner
    Department of Biological Chemistry, Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor, 48109 0650, USA
    J Biol Chem 281:21458-68. 2006
    ..We propose that eIF2alpha phosphorylation is fundamentally a death signal, yet it may promote either death or survival, depending upon coincident signaling events...
  48. pmc Low TRBP levels support an innate human immunodeficiency virus type 1 resistance in astrocytes by enhancing the PKR antiviral response
    Chi L Ong
    Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia
    J Virol 79:12763-72. 2005
    ..Our findings highlight TRBP as a novel cellular target for therapeutic interventions to block productive HIV-1 replication in cells that are fully permissive for HIV-1 infection...
  49. ncbi P58IPK, a novel endoplasmic reticulum stress-inducible protein and potential negative regulator of eIF2alpha signaling
    Rika van Huizen
    Laboratory of Cellular and Molecular Biology, National Institute on Aging NIH, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA
    J Biol Chem 278:15558-64. 2003
    ..These findings implicate P58(IPK) as an important component of a negative feedback loop used by the cell to inhibit eIF2alpha signaling, and thus attenuate the unfolded protein response...
  50. ncbi Binding of the influenza A virus NS1 protein to PKR mediates the inhibition of its activation by either PACT or double-stranded RNA
    Shoudong Li
    Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    Virology 349:13-21. 2006
    ..In addition, we demonstrated that PKR activation is inhibited in cells infected with a recombinant influenza A virus expressing NS1A mutant protein that cannot bind RNA, as is the case in cells infected with wild-type influenza A virus...
  51. pmc Isolation of the gene encoding the Drosophila melanogaster homolog of the Saccharomyces cerevisiae GCN2 eIF-2alpha kinase
    D S Olsen
    Department of Molecular Biology, Vanderbilt University, Nashville, Tennessee 37235, USA
    Genetics 149:1495-509. 1998
    ..Drosophila and other higher eukaryotes. Despite these differences, the presence of GCN2 in Drosophila suggests at least partial conservation from yeast to multicellular organisms of the mechanisms responding to amino acid deprivation...
  52. ncbi Critical role for the oligoadenylate synthetase/RNase L pathway in response to IFN-beta during acute ocular herpes simplex virus type 1 infection
    Bobbie Ann Austin
    Department of Ophthalmology, University of Oklahoma Health Sciences Center, Biomedical Sciences Building, 608 Stanton L Young Boulevard, Oklahoma City, OK 73104, USA
    J Immunol 175:1100-6. 2005
    ....
  53. ncbi Small molecule inhibitors of the RNA-dependent protein kinase
    Narasimham V Jammi
    Department of Chemistry, University of Utah, Salt Lake City, UT 84112, USA
    Biochem Biophys Res Commun 308:50-7. 2003
    ..This assay can be carried out with added exogenous human PKR to study the effect of various compounds in their ability to rescue the translational block imposed by human PKR...
  54. ncbi Evidence that hepatitis C virus resistance to interferon is mediated through repression of the PKR protein kinase by the nonstructural 5A protein
    M J Gale
    Department of Microbiology, University of Washington, Seattle 98195, USA
    Virology 230:217-27. 1997
    ..Thus, inactivation of PKR may be one mechanism by which HCV avoids the antiviral effects of IFN. Finally the inhibition of the PKR protein kinase, by NS5A is the first described function for this HCV protein...
  55. pmc Translation regulation by eukaryotic initiation factor-2 kinases in the development of latent cysts in Toxoplasma gondii
    Jana Narasimhan
    Department of Pharmacology and Toxicology and Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
    J Biol Chem 283:16591-601. 2008
    ..Given its importance to pathogenesis, eIF2 kinase-mediated stress responses may provide opportunities for novel therapeutics...
  56. ncbi Coping with stress: eIF2 kinases and translational control
    R C Wek
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
    Biochem Soc Trans 34:7-11. 2006
    ....
  57. ncbi The unfolded protein response: a stress signaling pathway critical for health and disease
    Kezhong Zhang
    Department of Biological Chemistry, Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor, MI 48109, USA
    Neurology 66:S102-9. 2006
    ..This review summarizes the complex regulation of UPR signaling and its relevance to human physiology and disease...
  58. pmc Suppression of RNA interference by adenovirus virus-associated RNA
    M Gunnar Andersson
    Department of Medical Biochemistry and Microbiology, Uppsala Biomedical Center, Sweden
    J Virol 79:9556-65. 2005
    ..In summary, our work shows that adenovirus suppresses RNAi during a lytic infection and gives insight into the mechanisms of RNAi suppression by VA RNA...
  59. pmc Double-stranded RNA-activated protein kinase PKR of fishes and amphibians: varying the number of double-stranded RNA binding domains and lineage-specific duplications
    Stefan Rothenburg
    Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    BMC Biol 6:12. 2008
    ..Fish and amphibian PKR genes have not been described so far...
  60. pmc Virus-induced unfolded protein response attenuates antiviral defenses via phosphorylation-dependent degradation of the type I interferon receptor
    Jianghuai Liu
    Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Cell Host Microbe 5:72-83. 2009
    ..These data suggest that specific activation of the PERK component of UPR can favor viral replication. Interfering with PERK-dependent IFNAR1 degradation could therefore contribute to therapeutic strategies against viral infections...
  61. ncbi Brain ischemia and reperfusion activates the eukaryotic initiation factor 2alpha kinase, PERK
    R Kumar
    Department of Emergency Medicine, Wayne State University, Detroit, Michigan 48201, USA
    J Neurochem 77:1418-21. 2001
    ....
  62. pmc Pancreatic eukaryotic initiation factor-2alpha kinase (PEK) homologues in humans, Drosophila melanogaster and Caenorhabditis elegans that mediate translational control in response to endoplasmic reticulum stress
    R Sood
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
    Biochem J 346:281-93. 2000
    ..These results suggest that decreased translation initiation by PEK during ER stress may provide the cell with an opportunity to remedy the folding problem prior to introducing newly synthesized proteins into the secretory pathway...
  63. ncbi Nuclear factor 90 is a substrate and regulator of the eukaryotic initiation factor 2 kinase double-stranded RNA-activated protein kinase
    L M Parker
    Department of Biochemistry and Molecular Biology, New Jersey Medical School, University of Medicine and Dentistry, New Jersey, Newark, New Jersey 07103 2714, USA
    J Biol Chem 276:32522-30. 2001
    ..The C-terminal region also inhibits PKR function, probably through competitive binding to dsRNA. A model for NF90-PKR interactions is proposed...
  64. pmc Protein kinase PKR plays a stimulus- and virus-dependent role in apoptotic death and virus multiplication in human cells
    Ping Zhang
    Department of Molecular, Cellular and Developmental Biology and Biomolecular Sciences and Engineering Program, University of California, Santa Barbara, CA 93106, USA
    J Virol 81:8192-200. 2007
    ..Surprisingly, the yield of mutant adenovirus that fails to encode VAI RNA was not enhanced in PKR-deficient cells, indicating the importance of host factors in addition to PKR in conferring the VAI RNA phenotype...
  65. pmc Nucleoside modifications modulate activation of the protein kinase PKR in an RNA structure-specific manner
    Subba Rao Nallagatla
    Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802, USA
    RNA 14:1201-13. 2008
    ..Overall, the findings indicate that nucleoside modifications and wobble pairing may serve to discriminate self-RNA and pathogenic RNA in innate immunity...
  66. pmc Hypoxia-induced energy stress regulates mRNA translation and cell growth
    Liping Liu
    Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, 421 Curie Boulevard, Philadelphia, Pennsylvania 19104, USA
    Mol Cell 21:521-31. 2006
    ..Together, eIF2alpha, eEF2, and mTOR inhibition represent important HIF-independent mechanisms of energy conservation that promote survival under low O2 conditions...
  67. pmc Hepatitis C virus blocks interferon effector function by inducing protein kinase R phosphorylation
    Urtzi Garaigorta
    Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA
    Cell Host Microbe 6:513-22. 2009
    ..These results suggest that the ability of HCV to activate PKR may, paradoxically, be advantageous for the virus during an IFN response by preferentially suppressing the translation of ISGs...
  68. ncbi Activation of the cell stress kinase PKR in Alzheimer's disease and human amyloid precursor protein transgenic mice
    Alyson L Peel
    Buck Institute for Age Research, Novato, CA, USA
    Neurobiol Dis 14:52-62. 2003
    ..These findings support a role for PKR activation in the pathogenesis of AD...
  69. ncbi PERK EIF2AK3 control of pancreatic beta cell differentiation and proliferation is required for postnatal glucose homeostasis
    Wei Zhang
    Department of Biology, Pennsylvania State University, University Park, Pennsylvania 16802, USA
    Cell Metab 4:491-7. 2006
    ....
  70. pmc The unfolded protein response is activated in pretangle neurons in Alzheimer's disease hippocampus
    Jeroen J M Hoozemans
    VU University Medical Center, Department of Pathology, P O Box 7057, 1007 MB Amsterdam, The Netherlands
    Am J Pathol 174:1241-51. 2009
    ....
  71. ncbi Translational control and the unfolded protein response
    Ronald C Wek
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
    Antioxid Redox Signal 9:2357-71. 2007
    ....
  72. ncbi PKR and eIF2alpha: integration of kinase dimerization, activation, and substrate docking
    Susan S Taylor
    Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla 92093, USA
    Cell 122:823-5. 2005
    ..The structures, coupled with mutagenesis analysis, also demonstrate how phosphorylation of the activation loop can allosterically couple two distal regions, the dimerization and substrate recognition interfaces...
  73. pmc Translational repression mediates activation of nuclear factor kappa B by phosphorylated translation initiation factor 2
    Jing Deng
    New York University Medical Center, SI 3 10, 540 First Ave, New York, NY 10016, USA
    Mol Cell Biol 24:10161-8. 2004
    ..These studies suggest a direct role for eIF2alpha phosphorylation-dependent translational control in activating NF-kappaB during ER stress...
  74. pmc West Nile virus-induced interferon production is mediated by the double-stranded RNA-dependent protein kinase PKR
    Felicia D Gilfoy
    Department of Pathology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555 0436, USA
    J Virol 81:11148-58. 2007
    ..Taken together, our data suggest that PKR could serve as a PRR for recognition of WNV infection...
  75. 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...
  76. ncbi The Atlantic salmon Z-DNA binding protein kinase phosphorylates translation initiation factor 2 alpha and constitutes a unique orthologue to the mammalian dsRNA-activated protein kinase R
    Veronica Bergan
    The Norwegian College of Fishery Science, University of Tromsø, Norway
    FEBS J 275:184-97. 2008
    ..Overall, the results support a role for PKZ, like PKR, in host defense against virus infection...
  77. pmc The 3'-untranslated regions of cytoskeletal muscle mRNAs inhibit translation by activating the double-stranded RNA-dependent protein kinase PKR
    Jean M Nussbaum
    Department of Biochemistry and Molecular Biology, New Jersey Medical School, UMDNJ, 185 South Orange Avenue, Newark, NJ 07103 2714, USA
    Nucleic Acids Res 30:1205-12. 2002
    ..These data are consistent with a mechanism whereby PKR mediates the differentiation- and tumor-related actions of the cytoskeletal 3'-UTR sequences...
  78. ncbi Serine 18 phosphorylation of RAX, the PKR activator, is required for PKR activation and consequent translation inhibition
    Richard L Bennett
    University of Florida College of Medicine, Shands Cancer Center, Gainesville, Florida 32610, USA
    J Biol Chem 279:42687-93. 2004
    ..We propose that the ability of RAX to activate PKR is regulated by a sequential mechanism featuring RAX association with PKR, RAX phosphorylation at serine 18, and activation of PKR...
  79. ncbi Dominant negative function by an alternatively spliced form of the interferon-inducible protein kinase PKR
    S Li
    Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, , , Canada
    J Biol Chem 276:13881-90. 2001
    ..Thus, expression of alternatively spliced forms of PKR may represent a novel mechanism of PKR autoregulation with important implications in the control of cell proliferation...
  80. pmc Controlling activation of the RNA-dependent protein kinase by siRNAs using site-specific chemical modification
    Sujiet Puthenveetil
    Department of Chemistry, University of Utah, Salt Lake City, UT 84112, USA
    Nucleic Acids Res 34:4900-11. 2006
    ..Thus, these studies demonstrate that specific positions in an siRNA can be rationally modified to prevent interaction with components of cellular dsRNA-regulated pathways...
  81. ncbi Immunohistochemical localization of phosphorylated protein kinase R and phosphorylated eukaryotic initiation factor-2 alpha in the central nervous system of SJL mice with experimental allergic encephalomyelitis
    Anuradha Chakrabarty
    Department of Molecular and Integrative Physiology, Mental Retardation and Human Development Center, University of Kansas Medical Center, Kansas City, 66160, USA
    J Neurosci Res 76:822-33. 2004
    ..The expression of phospho-eIF2 alpha in oligodendrocytes during EAE likely is involved with inhibition of protein translation, which is a protective mechanism used to promote cell survival in response to inflammation...
  82. ncbi The unfolded protein response is activated in Alzheimer's disease
    J J M Hoozemans
    Neurogenetics Laboratory, Academic Medical Center, University of Amsterdam, P O Box 22660, 1100 DD, Amsterdam, The Netherlands
    Acta Neuropathol 110:165-72. 2005
    ..Although the initial participation of the UPR in AD pathogenesis might be neuroprotective, sustained activation of the UPR in AD might initiate or mediate neurodegeneration...
  83. pmc Tumor cell dormancy induced by p38SAPK and ER-stress signaling: an adaptive advantage for metastatic cells?
    Aparna C Ranganathan
    Department of Biomedical Sciences, School of Public Health and Center for Excellence in Cancer Genomics, University at Albany, State University of New York, Rensselaer, NY 12144 3456, USA
    Cancer Biol Ther 5:729-35. 2006
    ..Finally, we propose that this response may recapitulate an evolutionarily conserved program of life-span extension through adaptation and tolerance to stress...
  84. ncbi Expression of unphosphorylated form of human double-stranded RNA-activated protein kinase in Escherichia coli
    T Matsui
    Department of Biochemistry, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan
    Biochem Biophys Res Commun 284:798-807. 2001
    ..The coexpression system of protein kinase with lambda-PPase described here will be applicable to obtaining unphosphorylated and unactivated forms of other protein kinases...
  85. pmc Identification of the heparin-binding domains of the interferon-induced protein kinase, PKR
    Stephen Fasciano
    Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA
    FEBS J 272:1425-39. 2005
    ..In addition, these mutants were defective in kinase activity as determined by both in vitro and in vivo assays...
  86. pmc Phosphorylation of the RNA-dependent protein kinase regulates its RNA-binding activity
    N V Jammi
    Department of Chemistry, University of Utah, Salt Lake City, UT 84112, USA
    Nucleic Acids Res 29:3020-9. 2001
    ..These results are consistent with an activation mechanism that includes release of the activating RNA upon autophosphorylation of PKR prior to phosphorylation of eIF2alpha...
  87. pmc Human cytomegalovirus infection activates and regulates the unfolded protein response
    Jennifer A Isler
    Department of Cancer Biology, Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, USA
    J Virol 79:6890-9. 2005
    ..These results suggest that, although HCMV infection induces the unfolded protein response, it modifies the outcome to benefit viral replication...
  88. pmc Viral dsRNA inhibitors prevent self-association and autophosphorylation of PKR
    Sean A McKenna
    Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305 5126, USA
    J Mol Biol 372:103-13. 2007
    ..These data indicate that inhibitory dsRNAs bind preferentially to the latent, dephosphorylated form of PKR and prevent dimerization that is required for trans-autophosphorylation...
  89. pmc Physical association between STAT1 and the interferon-inducible protein kinase PKR and implications for interferon and double-stranded RNA signaling pathways
    A H Wong
    Department of Oncology, McGill University, Montreal, Quebec, Canada
    EMBO J 16:1291-304. 1997
    ..These findings suggest that PKR plays an important role in IFN and dsRNA-signaling pathways by modulating the transcriptional function of STAT1...
  90. pmc Cytoprotection by pre-emptive conditional phosphorylation of translation initiation factor 2
    Phoebe D Lu
    Skirball Institute, New York University School of Medicine, New York, NY, USA
    EMBO J 23:169-79. 2004
    ....
  91. pmc Protein synthesis and endoplasmic reticulum stress can be modulated by the hepatitis C virus envelope protein E2 through the eukaryotic initiation factor 2alpha kinase PERK
    Nicole Pavio
    Howard Hughes Medical Institute, Department of Molecular Microbiology and Immunology, School of Medicine, University of Southern California, Los Angeles, California 90033, USA
    J Virol 77:3578-85. 2003
    ..These findings may also explain how the virus promotes persistent infection by overcoming the cellular ER stress response...
  92. ncbi Inhibition of glioma growth by tumor-specific activation of double-stranded RNA-dependent protein kinase PKR
    Alexei Shir
    Unit of Cellular Signaling, Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Givat Ram, Jerusalem 91904, Israel
    Nat Biotechnol 20:895-900. 2002
    ..This PKR-mediated killing strategy may be useful in treating many cancers that express a unique RNA species...
  93. 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...
  94. ncbi Vaccinia virus recombinants as a model system to analyze interferon-induced pathways
    Jesus Gil
    Department of Molecular and Cellular Biology, Centro Nacional de Biotecnologia, Consejo Superior de Investigaciones Cientificas, Campus Universidad Autonoma, 28049 Madrid, Spain
    J Interferon Cytokine Res 24:637-46. 2004
    ....
  95. pmc Control of PERK eIF2alpha kinase activity by the endoplasmic reticulum stress-induced molecular chaperone P58IPK
    Wei Yan
    Departments of Microbiology and Laboratory Medicine, School of Medicine, and Washington National Primate Research Center, University of Washington, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 99:15920-5. 2002
    ..Our studies suggest that P58(IPK) induction during the ER-stress response represses PERK activity and plays a functional role in the expression of downstream markers of PERK activity in the later phase of the ER-stress response...
  96. pmc Heterologous dimerization domains functionally substitute for the double-stranded RNA binding domains of the kinase PKR
    T L Ung
    Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    EMBO J 20:3728-37. 2001
    ....
  97. ncbi Endoplasmic reticulum stress features are prominent in Alzheimer disease but not in prion diseases in vivo
    Ursula Unterberger
    Institute of Neurology, Medical University of Vienna, Austria
    J Neuropathol Exp Neurol 65:348-57. 2006
    ..The lack of prominent activation of the PERK-eIF2alpha pathway in prion diseases suggests that, in contrast to AD, ER stress does not play a crucial role in neuronal death in prion disorders...
  98. pmc Orchestrating the unfolded protein response in health and disease
    Randal J Kaufman
    Department of Biological Chemistry, Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor 48109 0650, USA
    J Clin Invest 110:1389-98. 2002
  99. ncbi Interferon action in triply deficient mice reveals the existence of alternative antiviral pathways
    A Zhou
    The Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA
    Virology 258:435-40. 1999
    ..These results confirm the antiviral functions of RNase L and PKR in vivo but also provide unequivocal evidence for the existence of novel, innate immune pathways against viruses...
  100. ncbi Mechanism of interferon action: cDNA structure, expression, and regulation of the interferon-induced, RNA-dependent P1/eIF-2 alpha protein kinase from human cells
    D C Thomis
    Department of Biological Sciences, University of California, Santa Barbara 93106
    Virology 188:33-46. 1992
    ..The amino-terminal half of the P1 protein did not possess conserved kinase motifs, but did show extensive homology with vaccinia virus-predicted protein E3L...
  101. ncbi GLP-1 receptor activation improves beta cell function and survival following induction of endoplasmic reticulum stress
    Bernardo Yusta
    Department of Medicine, Banting and Best Diabetes Centre, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
    Cell Metab 4:391-406. 2006
    ..These findings demonstrate that GLP-1R signaling directly modulates the ER stress response leading to promotion of beta cell adaptation and survival...

Research Grants62

  1. INTERFERON ANIMAL VIRUSES AND PROTEIN SYNTHESIS
    Peter Lengyel; Fiscal Year: 1999
    ....
  2. PROTEIN SYNTHESIS INITIATION IN YEAST (S. CEREVISIAE)
    NABA GUPTA; Fiscal Year: 1993
    ....
  3. TRANSLATION INITIATION IN MULTICELLULAR EUKARYOTES
    Douglas Cavener; Fiscal Year: 2002
    ..abstract_text> ..
  4. Anti-Viral Gene Delivery in the Nervous System
    Daniel Carr; Fiscal Year: 2005
    ..abstract_text> ..
  5. The Role of CXCL9 in Genital HSV-2 Infection
    Daniel Carr; Fiscal Year: 2009
    ..g., vaccine or gene transfer) to reduce the incidence of infection or reduce the capacity of latent virus to reactivate. ..
  6. NEUROIMMUNOLOGY OF AED IN OCULAR HSV-1 INFECTION
    Daniel Carr; Fiscal Year: 2001
    ..abstract_text> ..
  7. 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]..
  8. Unfolded proteins in the Endoplasmic Reticulum to Disease
    Randal Kaufman; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  9. IMMUNOBIOLOGY OF AGING IN GENETICALLY ALTERED MICE
    Warren Ladiges; Fiscal Year: 2004
    ....
  10. GENE EXPRESSION PROFILING OF AIDS VACCINE STRATEGIES
    Michael Katze; Fiscal Year: 2007
    ..Ultimately, these studies may also suggest mechanisms to enhance current AIDS vaccine strategies. [unreadable] [unreadable] [unreadable]..
  11. Proteomic Analysis of the Innate Antiviral Response
    Michael Katze; Fiscal Year: 2004
    ..abstract_text> ..
  12. Comparative Mouse Genomics Center
    Warren Ladiges; Fiscal Year: 2006
    ....
  13. HEPATITIS C VIRUS:PATHOGENESIS AND CELLULAR SIGNALING
    Michael Katze; Fiscal Year: 2005
    ..Identification of the kinase will likely help decipher the detailed molecular pathways uncovered from these studies. These studies may contribute to the identification of novel cellular gene targets for anti-HCV therapeutics. ..
  14. 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. ..
  15. Gene Expression Profiling in Filovirus-Infected Cells
    Michael Katze; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable]..
  16. Microarray Analysis of Translational Regulatory Pathways
    Michael Katze; Fiscal Year: 2003
    ..The proposed studies make use of technologies not available at the time of the parent grant award and will allow us to capitalize on recent findings and extend our studies in new directions. ..
  17. Alzheimer's Disease and Impaired APP Proteolysis
    Warren Ladiges; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  18. TRANSLATIONAL CONTROL IN INFLUENZA VIRUS INFECTED CELLS
    Michael Katze; Fiscal Year: 2009
    ..The identification of host pathways impacted by influenza virus should reveal novel therapeutic targets and lead to improved antiviral therapies and vaccines. ..
  19. TRANSLATIONAL CONTROL IN REGULATION OF APOPTOSIS
    Randal Kaufman; Fiscal Year: 2002
    ....
  20. High Throughput Chemical Genomics to Identify Novel Inhibitors of CHOP
    Randal Kaufman; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  21. 3rd International Conference on Primate Genomics
    Michael Katze; Fiscal Year: 2008
    ..Importantly, this conference will also highlight research activities in which genomics and nonhuman primate models are being used to better understand, prevent, and treat human disease. [unreadable] [unreadable] [unreadable]..
  22. 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]..
  23. 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. ..
  24. HEPATITIS C VIRUS AND INTERFERON--CONTROL OF PKR BY NS5A
    Michael Katze; Fiscal Year: 2001
    ..3) Identification of NS5A phosphorylation sites in vivo. The importance of such sites for NS5A function will be examined by site-directed mutagenesis. ..
  25. Macaque Model and Gene Expression Profiling of SARS
    Michael Katze; Fiscal Year: 2009
    ..Such knowledge may lead to new diagnostic, therapeutic, or vaccine strategies, which may serve as important countermeasures to future SARS outbreaks. ..
  26. TRANSGENIC ANIMAL MODEL DEVELOPMENT--PKR PROTEIN KINASE
    Warren Ladiges; Fiscal Year: 2001
    ..abstract_text> ..
  27. Centrifrugal analysis of complex hetero-interactions
    James Cole; Fiscal Year: 2006
    ..The analysis package, along with documentation and tutorials, will be freely available over the internet. [unreadable] [unreadable]..
  28. Molecular Mechanism of HIV-1 Vif Function
    BRYAN CULLEN; Fiscal Year: 2007
    ..Together, this wide-ranging series of experiments should lead to considerable insight into how HIV-1 Vif functions and potentially suggest approaches to inhibit Vif function. ..
  29. PATHOGENIC MECHANISMS OF PRESENILIN MUTATION
    Robert Siman; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  30. Innate immune evasion and/or antagonism by eastern equine encephalitis virus
    KATHERINE RYMAN; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  31. Hepatitis C Virus Induced IL-8 & Inhibition of Interferon
    STEPHEN POLYAK; Fiscal Year: 2007
    ..Moreover, IL-8 or its receptors may prove to be suitable targets for therapeutic intervention in chronic hepatitis C. ..
  32. 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]..
  33. T Regulatory Cells and Childhood Asthma
    James Gern; Fiscal Year: 2008
    ..abstract_text> ..
  34. Subversion of innate immune responses by Brucella
    Sankar Ghosh; Fiscal Year: 2006
    ..We are therefore proposing to characterize the role of TIRB in Brucella infection and we believe that our studies will help in the future development of therapeutic strategies, including vaccination, against human infection by Brucella. ..
  35. The Unfolded Protein Response After Brain Ischemia
    DONALD DEGRACIA; Fiscal Year: 2006
    ..abstract_text> ..
  36. Mucosal Immunization with a Vaccinia Virus-Based Vector
    Bertram Jacobs; Fiscal Year: 2003
    ..Animals will be immunized intra-nasally either with virus alone or as part of a prime-boost regime. Systemic, nasal and vaginal immune responses to the HIV multi-epitope polypeptide will be analyzed. ..
  37. Bacterial artificial chromosomes for HSV genomics
    David Leib; Fiscal Year: 2004
    ..abstract_text> ..
  38. Ebola VP35 mediated viral mechanisms
    Bin He; Fiscal Year: 2004
    ..abstract_text> ..
  39. GCN5-mediated transcription in AIDS pathogen Toxoplasma
    WILLIAM SULLIVAN JR; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  40. Pathogenesis of Macrophage Tropic HIV-1
    Paul Gorry; Fiscal Year: 2004
    ..Understanding the molecular basis of enhanced M-tropism will provide further insights into HIV-1 pathogenesis, which is vital for the development of new inhibitors for the treatment of HIV-1 infection. ..
  41. An Improved Vaccine for Protection Against Smallpox
    Bertram Jacobs; Fiscal Year: 2003
    ..Strains will be analyzed in mice for pathogenesis and for induction of a protective immune response. ..
  42. HIV-1 TROPISM AND CHEMOKINE RECEPTORS
    BRYAN CULLEN; Fiscal Year: 2002
    ..The final specific aim focusses on the promoter regions of CCR5, the identification of transcription factors that may interact with the promoter, and the use of antisense strategies to block CCR5 expression. ..
  43. REGULATION OF PROTEIN TURNOVER IN SEPSIS
    Scot R Kimball; Fiscal Year: 2010
    ....
  44. Ad-mda7 plus Herceptin against Breast Cancer
    Sunil Chada; Fiscal Year: 2002
    ..This strategy, if successful, could be further applied in human breast cancer trials. ..
  45. HUMAN GLOBIN GENE TRANSFER AND EXPRESSION
    Arthur Bank; Fiscal Year: 2002
    ....
  46. A FADD-Associated Helicase Essential for Host Defense
    Glen Barber; Fiscal Year: 2008
    ..We anticipate that these studies will improve our knowledge of pathogenesis and provide new concepts for the rational design of novel therapeutic and vaccine strategies. [unreadable] [unreadable] [unreadable]..
  47. REPETITIVE DNA SEQUENCES IN THE HUMAN GENOME
    CARL SCHMID; Fiscal Year: 2002
    ..abstract_text> ..
  48. Targeted Therapy for Burkitt Lymphoma in Resource Poor Settings
    Glen N Barber; Fiscal Year: 2010
    ..Our long term goal is to develop a targeted, efficacious, antiviral-based therapy for EBV (HIV) associated lymphoma that is applicable in developing nations. ..
  49. 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. ..
  50. 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. ..
  51. Role of PKR in Growth Regulation
    Glen Barber; Fiscal Year: 2008
    ..We propose that these aims will lend insight into mechanisms of cell signaling, tumorigenesis and interferon-mediated actions in the cell. ..
  52. Nanoparticles for the Treatment of Lung Cancer
    Mingzhong Zheng; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  53. REGULATION OF HUMAN GLOBIN GENE EXPRESSION
    Arthur Bank; Fiscal Year: 2004
    ..abstract_text> ..
  54. Hepatitis C Virus Proteins and Ethanol
    STEPHEN POLYAK; Fiscal Year: 2004
    ..abstract_text> ..
  55. Immunogenicity of Hepatitis C Virus (HCV) like particles
    Glen Barber; Fiscal Year: 2007
    ..abstract_text> ..
  56. Regulation of HIV transcription by Tat and P-TEPb
    TSAFI PE ERY; Fiscal Year: 2004
    ..We will explore the ability of HIC and granulin to regulate transactivation of the HIV promoter and define the sequences of these proteins necessary for binding to cyclin T1 and Tat. ..
  57. Development of a Safer Smallpox Vaccine
    Bertram Jacobs; Fiscal Year: 2007
    ..abstract_text> ..
  58. Gene Delivery into Human Hematopoietic Cells
    Arthur Bank; Fiscal Year: 2008
    ..The gene delivery technology should also be applicable for use in treating other human diseases as well. ..
  59. FUNCTION ANALYSIS OF THE DSRNA REGULATED NUCLEAR FACTORS
    Glen Barber; Fiscal Year: 2004
    ..abstract_text> ..
  60. Mechanisms of VSV-mediated Oncolysis
    Glen N Barber; Fiscal Year: 2010
    ..Understanding how these pathways function has significant impact on understanding pathogenesis and for developing novel therapeutics and vaccines to combat disease. ..