Dif

Summary

Gene Symbol: Dif
Description: Dorsal-related immunity factor
Alias: 6794, CG6794, DIF, Dmel\CG6794, dif, CG6794 gene product from transcript CG6794-RD, CG6794-PA, CG6794-PB, CG6794-PC, CG6794-PD, Dif-PA, Dif-PB, Dif-PC, Dif-PD, Dorsal-like immunity factor, Dorsal-related transcription factor, dorsal related immunity factor, dorsal-related immunity factor
Species: fruit fly

Top Publications

  1. pmc DEAF-1 regulates immunity gene expression in Drosophila
    Darien E Reed
    Helen Diller Family Comprehensive Cancer Center and Cancer Research Institute, University of California, San Francisco, CA 94115 0128, USA
    Proc Natl Acad Sci U S A 105:8351-6. 2008
  2. pmc Short-term starvation of immune deficient Drosophila improves survival to gram-negative bacterial infections
    Anthony E Brown
    Genetics Unit Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    PLoS ONE 4:e4490. 2009
  3. pmc Prophenoloxidase activation is not required for survival to microbial infections in Drosophila
    Vincent Leclerc
    UPR9022 du CNRS, IBMC, 15 rue Descartes, 67084 Strasbourg, France
    EMBO Rep 7:231-5. 2006
  4. ncbi The immune response of Drosophila
    Jules A Hoffmann
    Institut de Biologie Moleculaire et Cellulaire du CNRS, 67084 Strasbourg Cedex, France
    Nature 426:33-8. 2003
  5. ncbi Dif, a dorsal-related gene that mediates an immune response in Drosophila
    Y T Ip
    Department of Biology, University of California, San Diego, La Jolla 92093 0322
    Cell 75:753-63. 1993
  6. pmc Origins of immunity: Relish, a compound Rel-like gene in the antibacterial defense of Drosophila
    M S Dushay
    Department of Developmental Biology, Stockholm University, Sweden
    Proc Natl Acad Sci U S A 93:10343-7. 1996
  7. ncbi Antimicrobial peptide defense in Drosophila
    M Meister
    UPR 9022, Institut de Biologie Moleculaire et Cellulaire, Strasbourg, France
    Bioessays 19:1019-26. 1997
  8. ncbi Regulated nuclear import of Rel proteins in the Drosophila immune response
    L P Wu
    Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Nature 392:93-7. 1998
  9. ncbi A role for the Drosophila Toll/Cactus pathway in larval hematopoiesis
    P Qiu
    Biology Department, City College, New York, NY 10031, USA
    Development 125:1909-20. 1998
  10. ncbi The Dorsal-related immunity factor (Dif) can define the dorsal-ventral axis of polarity in the Drosophila embryo
    D Stein
    Department of Molecular Genetics and Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA
    Development 125:2159-69. 1998

Research Grants

  1. Evolutionary Genomics of Anti-Malaria Genes in Mosquito
    Brian P Lazzaro; Fiscal Year: 2010
  2. TOLL RECEPTORS AND CONTROL OF MAMMALIAN IMMUNITY
    Ruslan Medzhitov; Fiscal Year: 2005

Scientific Experts

Detail Information

Publications109 found, 100 shown here

  1. pmc DEAF-1 regulates immunity gene expression in Drosophila
    Darien E Reed
    Helen Diller Family Comprehensive Cancer Center and Cancer Research Institute, University of California, San Francisco, CA 94115 0128, USA
    Proc Natl Acad Sci U S A 105:8351-6. 2008
    ..The coexpression of DEAF-1 with Dorsal, Dif, and Relish results in the synergistic activation of transcription...
  2. pmc Short-term starvation of immune deficient Drosophila improves survival to gram-negative bacterial infections
    Anthony E Brown
    Genetics Unit Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    PLoS ONE 4:e4490. 2009
    ..Since the TIR-NF-kappaB circuit is a conserved component of the host defence in higher animals, genetically tractable models may contribute ideas for clinical interventions...
  3. pmc Prophenoloxidase activation is not required for survival to microbial infections in Drosophila
    Vincent Leclerc
    UPR9022 du CNRS, IBMC, 15 rue Descartes, 67084 Strasbourg, France
    EMBO Rep 7:231-5. 2006
    ..This raises the question with regard to the precise function of phenoloxidase activation in defence, if any...
  4. ncbi The immune response of Drosophila
    Jules A Hoffmann
    Institut de Biologie Moleculaire et Cellulaire du CNRS, 67084 Strasbourg Cedex, France
    Nature 426:33-8. 2003
    ..Recent progress in research on Drosophila immune defence provides evidence for similarities and differences between Drosophila immune responses and mammalian innate immunity...
  5. ncbi Dif, a dorsal-related gene that mediates an immune response in Drosophila
    Y T Ip
    Department of Biology, University of California, San Diego, La Jolla 92093 0322
    Cell 75:753-63. 1993
    ..A novel Rel-containing gene in Drosophila, Dif (dorsal-related immunity factor), provides a potential link between these seemingly disparate processes...
  6. pmc Origins of immunity: Relish, a compound Rel-like gene in the antibacterial defense of Drosophila
    M S Dushay
    Department of Developmental Biology, Stockholm University, Sweden
    Proc Natl Acad Sci U S A 93:10343-7. 1996
    ..The presence of a compound Rel protein in Drosophila indicates that similar proteins were likely present in primordial immune systems and may serve unique signaling functions...
  7. ncbi Antimicrobial peptide defense in Drosophila
    M Meister
    UPR 9022, Institut de Biologie Moleculaire et Cellulaire, Strasbourg, France
    Bioessays 19:1019-26. 1997
    ..Recent data on the molecular mechanisms underlying recognition of non-self are also discussed in this review...
  8. ncbi Regulated nuclear import of Rel proteins in the Drosophila immune response
    L P Wu
    Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Nature 392:93-7. 1998
    ..In response to infection, two Rel proteins, Dif and Dorsal, translocate from the cytoplasm to the nuclei of larval fat-body cells...
  9. ncbi A role for the Drosophila Toll/Cactus pathway in larval hematopoiesis
    P Qiu
    Biology Department, City College, New York, NY 10031, USA
    Development 125:1909-20. 1998
    ..These findings are discussed in light of similar hematopoietic functions of Rel/I(kappa)B-family proteins in mice...
  10. ncbi The Dorsal-related immunity factor (Dif) can define the dorsal-ventral axis of polarity in the Drosophila embryo
    D Stein
    Department of Molecular Genetics and Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA
    Development 125:2159-69. 1998
    ..b>Dif, a more recently identified Drosophila Rel-homologue, has been proposed to act as a mediator of the immune response ..
  11. pmc Toll receptor-mediated Drosophila immune response requires Dif, an NF-kappaB factor
    X Meng
    Program in Molecular Medicine, Department of Cell Biology, and Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605 USA
    Genes Dev 13:792-7. 1999
    The induction of immunity genes in Drosophila has been proposed to be dependent on Dorsal, Dif, and Relish, the NF-kappaB-related factors...
  12. ncbi Phylogenetic perspectives in innate immunity
    J A Hoffmann
    Institute of Molecular and Cellular Biology, CNRS, Strasbourg, 67084, France
    Science 284:1313-8. 1999
    ..In addition to its role in the early phase of defense, innate immunity in mammals appears to play a key role in stimulating the subsequent, clonal response of adaptive immunity...
  13. pmc A mosaic analysis in Drosophila fat body cells of the control of antimicrobial peptide genes by the Rel proteins Dorsal and DIF
    P Manfruelli
    Institut de Biologie Moleculaire et Cellulaire, UPR 9022 du Centre National de la Recherche Scientifique, 15, rue René Descartes, F 67084 Strasbourg CEDEX, France
    EMBO J 18:3380-91. 1999
    ..The Rel proteins Dorsal and DIF (Dorsal-related immunity factor) are possible candidates for the transactivating protein in the Toll pathway that ..
  14. ncbi Interaction and specificity of Rel-related proteins in regulating Drosophila immunity gene expression
    Z S Han
    Program in Molecular Medicine, Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    J Biol Chem 274:21355-61. 1999
    ..Furthermore, the drosomycin and defensin expression is best induced by the Relish/Dif and the Relish/Dorsal heterodimers, respectively, whereas the attacin activity can be efficiently up-regulated by ..
  15. ncbi The Rel protein DIF mediates the antifungal but not the antibacterial host defense in Drosophila
    S Rutschmann
    Institut de Biologie Moleculaire et Cellulaire, UPR 9022 du CNRS, Strasbourg, France
    Immunity 12:569-80. 2000
    We have isolated two Drosophila lines that carry point mutations in the gene coding for the NF-KB-like factor DIF. Like mutants of the Toll pathway, Dif mutant flies are susceptible to fungal but not to bacterial infections...
  16. ncbi Role of Drosophila IKK gamma in a toll-independent antibacterial immune response
    S Rutschmann
    Institut de Biologie Moleculaire et Cellulaire, UPR 9022 du CNRS, 15, rue R Descartes, F67084 Strasbourg, France
    Nat Immunol 1:342-7. 2000
    ..However, it is not required for the Toll-DIF-dependent antifungal host defense...
  17. ncbi Microfluorometer assay to measure the expression of beta-galactosidase and green fluorescent protein reporter genes in single Drosophila flies
    A C Jung
    Centre National de la Recherche Scientifique, Strasbourg, France
    Biotechniques 30:594-8, 600-1. 2001
    ..This method may be used in any screen that requires the quantification of reporter gene activity in individual insects...
  18. ncbi Cactus-independent nuclear translocation of Drosophila RELISH
    W D Cornwell
    Department of Gene Expression Sciences, GlaxoSmithKline Pharmaceuticals, King of Prussia, Pennsylvania, USA
    J Cell Biochem 82:22-37. 2001
    ....
  19. ncbi Drosophila Toll is activated by Gram-positive bacteria through a circulating peptidoglycan recognition protein
    T Michel
    Institut de Biologie Moleculaire et Cellulaire, UPR 9022 du CNRS, 15 rue Rene Descartes, 67084 Strasbourg Cedex, France
    Nature 414:756-9. 2001
    ..Interestingly, seml does not affect Toll activation by fungal infection, indicating the existence of a distinct recognition system for fungi to activate the Toll pathway...
  20. ncbi Cutting edge: the toll pathway is required for resistance to gram-positive bacterial infections in Drosophila
    Sophie Rutschmann
    Institut de Biologie Moleculaire et Cellulaire, Unité Propre de Recherche 9022 du Centre National de la Recherche Scientifique, Strasbourg, France
    J Immunol 168:1542-6. 2002
    ..In this study, we report that the Toll pathway, but not that of immune deficiency, is required for resistance to other Gram-positive bacteria and that this response does not involve Defensin...
  21. ncbi Requirement for a peptidoglycan recognition protein (PGRP) in Relish activation and antibacterial immune responses in Drosophila
    Kwang Min Choe
    Molecular Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    Science 296:359-62. 2002
    ....
  22. ncbi The Drosophila immune response against Gram-negative bacteria is mediated by a peptidoglycan recognition protein
    Marie Gottar
    UPR 9022 du Centre National de la Recherche Scientifique, Institut de Biologie Moleculaire et Cellulaire, 15 rue Rene Descartes, F67084 Strasbourg, Cedex, France
    Nature 416:640-4. 2002
    ..The data on PGRP-SA with respect to the response to Gram-positive infections, together with the present report, indicate that the PGRP family has a principal role in sensing microbial infections in Drosophila...
  23. ncbi Activation of Drosophila Toll during fungal infection by a blood serine protease
    Petros Ligoxygakis
    Institut de Biologie Moleculaire et Cellulaire, UPR 9022 du CNRS, 15 rue R Descartes, F67084 Strasbourg Cedex, France
    Science 297:114-6. 2002
    ..We show that ethylmethane sulfonate-induced mutations in the persephone gene, which encodes a previously unknown serine protease, block induction of the Toll pathway by fungi and resistance to this type of infection...
  24. pmc Critical evaluation of the role of the Toll-like receptor 18-Wheeler in the host defense of Drosophila
    Petros Ligoxygakis
    Institut de Biologie Moléculaire and Cellulaire, Strasbourg Cedex, France
    EMBO Rep 3:666-73. 2002
    ..18-Wheeler does not qualify as a pattern recognition receptor of Gram-negative bacteria...
  25. pmc A serpin mutant links Toll activation to melanization in the host defence of Drosophila
    Petros Ligoxygakis
    Institut de Biologie Moléculaire and Cellulaire, UPR 9022 du CNRS, 15, rue René Descartes, F 67084 Strasbourg CEDEX, France
    EMBO J 21:6330-7. 2002
    ..Flies deficient for this serpin exhibit spontaneous melanization in larvae and adults. Microbial challenge induces its removal from the hemolymph through Toll-dependent transcription of an acute phase immune reaction component...
  26. ncbi Pherokine-2 and -3
    Laurence Sabatier
    CNRS UPR9022, Institut de Biologie Moleculaire et Cellulaire, Strasbourg, France
    Eur J Biochem 270:3398-407. 2003
    ..Both Phk-2 and Phk-3 are strongly expressed during metamorphosis, suggesting that they may participate in tissue-remodeling...
  27. pmc Discrete functions of TRAF1 and TRAF2 in Drosophila melanogaster mediated by c-Jun N-terminal kinase and NF-kappaB-dependent signaling pathways
    Guang Ho Cha
    National Creative Research Initiatives Center for Cell Growth Regulation, and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 373 1 Kusong Dong, Yusong, Taejon 305 701, Republic of Korea
    Mol Cell Biol 23:7982-91. 2003
    ..Ectopic expression of DTRAF2 induced nuclear translocation of two Drosophila NF-kappaBs, DIF and Relish, consequently activating the transcription of the antimicrobial peptide genes diptericin, diptericin-..
  28. pmc Functional characterization of a novel promoter element required for an innate immune response in Drosophila
    Hanna Uvell
    Department of Molecular Biology and Functional Genomics, Arrhenius Laboratories for Natural Sciences, Stockholm University, SE 106 91 Stockholm, Sweden
    Mol Cell Biol 23:8272-81. 2003
    ..The induced gene expression relies on translocation of the Drosophila Rel transcription factors Relish, Dif, and Dorsal to the nucleus where they bind to kappaB-like motifs in the promoters of the inducible genes...
  29. ncbi Dual activation of the Drosophila toll pathway by two pattern recognition receptors
    Vanessa Gobert
    Unité Propre de Recherche 9022 du CNRS, Institut de Biologie Moleculaire et Cellulaire, 15 rue Rene Descartes, F67084 Strasbourg Cedex, France
    Science 302:2126-30. 2003
    ..The potential for a combination of distinct proteins to mediate detection of infectious nonself in the fly will refine the concept of pattern recognition in insects...
  30. ncbi Immunity regulatory DNAs share common organizational features in Drosophila
    Kate Senger
    Department of Molecular and Cellular Biology, Division of Genetics and Development, University of California, Berkeley, Berkeley, CA 94720, USA
    Mol Cell 13:19-32. 2004
    ..Two classes of transcription factors have been implicated in this process: the REL-containing proteins, Dorsal, Dif, and Relish, and the GATA factor Serpent...
  31. ncbi Differential activation of the NF-kappaB-like factors Relish and Dif in Drosophila melanogaster by fungi and Gram-positive bacteria
    Marika Hedengren-Olcott
    Department of Zoology, Oregon State University, 220 Nash Hall, Corvallis, OR 97331, USA
    J Biol Chem 279:21121-7. 2004
    ..activation in Drosophila melanogaster suggests that fungi and Gram-positive (G(+)) bacteria activate the Toll/Dif pathway and that Gram-negative (G(-)) bacteria activate the Imd/Relish pathway...
  32. ncbi The roles of JAK/STAT signaling in Drosophila immune responses
    Herve Agaisse
    Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
    Immunol Rev 198:72-82. 2004
    ....
  33. ncbi Hemolymph-dependent and -independent responses in Drosophila immune tissue
    Raul Bettencourt
    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    J Cell Biochem 92:849-63. 2004
    ..Using GFP-Dorsal, -Dif, and -Relish reporter proteins in ex vivo assays, we demonstrate that Drosophila fat bodies, a major immune tissue, ..
  34. ncbi Function of the drosophila pattern-recognition receptor PGRP-SD in the detection of Gram-positive bacteria
    Vincent Bischoff
    Institut de Biologie Moleculaire et Cellulaire, CNRS UPR 9022, 15 rue Rene Descartes, Universite Louis Pasteur, 67084 Strasbourg Cedex, France
    Nat Immunol 5:1175-80. 2004
    ..These data indicate that PGRP-SD can function as a receptor for Gram-positive bacteria and shows partial redundancy with the PGRP-SA-GNBP1 complex...
  35. ncbi An epidermal barrier wound repair pathway in Drosophila is mediated by grainy head
    Kimberly A Mace
    Section of Cell and Developmental Biology, Division of Biology, University of California, San Diego, La Jolla, CA 92093, USA
    Science 308:381-5. 2005
    ..The conservation of this Grh-dependent pathway suggests that the repair of insect cuticle and mammal skin is controlled by an ancient, shared control system for constructing and healing the animal body surface barrier...
  36. pmc The Toll pathway is important for an antiviral response in Drosophila
    Robert A Zambon
    Center for Biosystems Research, University of Maryland Biotechnology Institute, College Park, MD 20742, USA
    Proc Natl Acad Sci U S A 102:7257-62. 2005
    ..Additionally, our results demonstrate the validity of using a genetic approach to identify genes and pathways used in viral innate immune responses in Drosophila...
  37. ncbi dUbc9 negatively regulates the Toll-NF-kappa B pathways in larval hematopoiesis and drosomycin activation in Drosophila
    Hsiling Chiu
    Department of Functional Genomics, Novartis Institutes for BioMedical Research, 100 Technology Square Bldg 601 Rm 6404, Cambridge, MA 02139, USA
    Dev Biol 288:60-72. 2005
    ..dUbc9 mutants are strongly suppressed in the absence of the Rel/NF-kappaB-family transcription factors Dorsal and Dif or in the presence of a non-signaling allele of Cactus, the IkappaB protein in Drosophila...
  38. ncbi Pathogen recognition and innate immunity
    Shizuo Akira
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    Cell 124:783-801. 2006
    ..New insights into innate immunity are changing the way we think about pathogenesis and the treatment of infectious diseases, allergy, and autoimmunity...
  39. ncbi Drosophila immunity: a large-scale in vivo RNAi screen identifies five serine proteases required for Toll activation
    Zakaria Kambris
    Centre de Genetique Moleculaire, CNRS, Gif sur Yvette, France
    Curr Biol 16:808-13. 2006
    ..These results demonstrate the existence of a common cascade of SPs upstream of Spz, integrating signals sent by various secreted recognition molecules via more specialized SPs...
  40. ncbi Two proteases defining a melanization cascade in the immune system of Drosophila
    Huaping Tang
    Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut 06520, USA
    J Biol Chem 281:28097-104. 2006
    ..We have also shown that the melanization reaction activated by MP1 and MP2 plays an important role in augmenting the effectiveness of other immune reactions, thereby promoting resistance of Drosophila to microbial infection...
  41. pmc Caspar, a suppressor of antibacterial immunity in Drosophila
    Myungjin Kim
    National Creative Research Initiatives Center for Cell Growth Regulation and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 373 1 Kusong Dong, Yusong, Taejon 305 701, Korea
    Proc Natl Acad Sci U S A 103:16358-63. 2006
    ..Collectively, our elucidation of an inhibitory mechanism of the Imd pathway by Caspar will provide a valuable insight into understanding complex regulatory mechanisms of the innate immune systems in both Drosophila and mammals...
  42. pmc Rel/NF-kappaB double mutants reveal that cellular immunity is central to Drosophila host defense
    Nina Matova
    Developmental Biology Program, Sloan Kettering Institute, 1275 York Avenue, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 103:16424-9. 2006
    ..Here we show that mutants that lack the Drosophila Rel/NF-kappaB proteins Dorsal and Dif have very few blood cells, are constitutively infected by opportunistic microbes, and die from infection as larvae...
  43. pmc Dual detection of fungal infections in Drosophila via recognition of glucans and sensing of virulence factors
    Marie Gottar
    UPR 9022 du CNRS, Institut de Biologie Moleculaire et Cellulaire, F67084 Strasbourg Cedex, France
    Cell 127:1425-37. 2006
    ..Thus, the detection of fungal infections in Drosophila relies both on the recognition of invariant microbial patterns and on monitoring the effects of virulence factors on the host...
  44. pmc Toll and IMD pathways synergistically activate an innate immune response in Drosophila melanogaster
    Takahiro Tanji
    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Mol Cell Biol 27:4578-88. 2007
    ..These results illustrate how specific ligand binding by separate upstream pattern recognition receptors can be translated into a broad-spectrum host response, a hallmark of innate immunity...
  45. ncbi Nematodes, bacteria, and flies: a tripartite model for nematode parasitism
    Elissa A Hallem
    Howard Hughes Medical Institute, Division of Biology, California Institute of Technology, Pasadena, California 91125, USA
    Curr Biol 17:898-904. 2007
    ....
  46. ncbi A Drosophila ortholog of the human cylindromatosis tumor suppressor gene regulates triglyceride content and antibacterial defense
    Theodore Tsichritzis
    Institute of Immunology, Biomedical Sciences Research Center Al Fleming, 34 Al Fleming Street, 16672 Vari, Greece
    Development 134:2605-14. 2007
    ..All mutant phenotypes described were reversible upon conditional expression of CYLD transgenes. Our results implicate CYLD in a broad range of functions associated with fat homeostasis and host defence in Drosophila...
  47. pmc NF-kappaB/Rel-mediated regulation of the neural fate in Drosophila
    Savita Ayyar
    Department of Zoology, University of Cambridge, Cambridge, United Kingdom
    PLoS ONE 2:e1178. 2007
    Two distinct roles are described for Dorsal, Dif and Relish, the three NF-kappaB/Rel proteins of Drosophila, in the development of the peripheral nervous system...
  48. pmc A model of bacterial intestinal infections in Drosophila melanogaster
    Nadine T Nehme
    Equipe Fondation Recherche Médicale, UPR 9022 du CNRS, Institut de Biologie Moleculaire et Cellulaire du CNRS, Strasbourg, France
    PLoS Pathog 3:e173. 2007
    ..Thanks to the genetic tools available in both host and pathogen, the molecular dissection of the interactions between S. marcescens and Drosophila will provide a useful paradigm for deciphering intestinal pathogenesis...
  49. doi Crystal structure of Drosophila PGRP-SD suggests binding to DAP-type but not lysine-type peptidoglycan
    Philippe Leone
    Architecture et Fonction des Macromolecules Biologiques, UMR 6098 CNRS and Universités Aix Marseille I and II, Marseille, France
    Mol Immunol 45:2521-30. 2008
    ..Our hypothesis is that the role of PGRP-SD is the recognition of DAP-type PGNs responsible for the activation of the Toll pathway by Gram-negative bacteria...
  50. pmc Peptidoglycan recognition protein-SD provides versatility of receptor formation in Drosophila immunity
    Lihui Wang
    Genetics Unit, Department of Biochemistry, South Parks Road, University of Oxford, Oxford OX1 3QU, United Kingdom
    Proc Natl Acad Sci U S A 105:11881-6. 2008
    ..These results indicate that the interplay between the binding affinities of different PGRPs provides sufficient flexibility for the recognition of the highly diverse Gram-positive PG...
  51. pmc A novel system for the launch of alphavirus RNA synthesis reveals a role for the Imd pathway in arthropod antiviral response
    Vasanthi Avadhanula
    Department of Biology, Indiana University, Bloomington, IN, USA
    PLoS Pathog 5:e1000582. 2009
    ..These findings show that the Imd pathway mediates an antiviral response to Sindbis virus replication. To our knowledge, this is the first demonstration of an antiviral role for the Imd pathway in insects...
  52. pmc The immune response attenuates growth and nutrient storage in Drosophila by reducing insulin signaling
    Justin R DiAngelo
    The Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 106:20853-8. 2009
    ..These data suggest that communication between these two regulatory systems evolved as a means to divert energy in times of need from organismal growth to the acute requirement of combating infection...
  53. pmc Drosophila Rel proteins are central regulators of a robust, multi-organ immune network
    Nina Matova
    Developmental Biology Program, Sloan Kettering Institute, New York, NY 10065, USA
    J Cell Sci 123:627-33. 2010
    ..In Drosophila, opportunistic infection kills larvae if they lack the Rel/NF-kappaB proteins Dorsal and Dif. We have used tissue-specific expression of Dif and Dorsal to reveal that these Rel proteins act in three different ..
  54. pmc The Drosophila PRR GNBP3 assembles effector complexes involved in antifungal defenses independently of its Toll-pathway activation function
    Alexey A Matskevich
    Equipe Fondation Recherche Médicale, UPR 9022 du CNRS, Université de Strasbourg Institut de Biologie Moléculaire et Cellulaire, Strasbourg Cedex, France
    Eur J Immunol 40:1244-54. 2010
    ..We propose that Drosophila GNBP3 targets fungi immediately at the inception of the infection by bringing effector molecules in direct contact with the invading microorganisms...
  55. pmc Heterodimers of NF-kappaB transcription factors DIF and Relish regulate antimicrobial peptide genes in Drosophila
    Takahiro Tanji
    Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Proc Natl Acad Sci U S A 107:14715-20. 2010
    ..Dorsal and DIF act downstream of Toll, whereas Relish acts downstream of IMD to regulate target gene expression...
  56. pmc Host and pathogen glycosaminoglycan-binding proteins modulate antimicrobial peptide responses in Drosophila melanogaster
    Zhipeng Wang
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, 181 Longwood Avenue, Boston, MA 02115, USA
    Infect Immun 79:606-16. 2011
    ....
  57. pmc Role for sumoylation in systemic inflammation and immune homeostasis in Drosophila larvae
    Indira Paddibhatla
    Biology Department, The Graduate Center, The City College of the City University of New York, New York, New York, United States of America
    PLoS Pathog 6:e1001234. 2010
    ....
  58. pmc Evolutionary conserved regulation of HIF-1β by NF-κB
    Patrick van Uden
    Wellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee, United Kingdom
    PLoS Genet 7:e1001285. 2011
    ..These results reveal a novel mechanism of HIF regulation, with impact in the development of novel therapeutic strategies for HIF-related pathologies including ageing, ischemia, and cancer...
  59. doi The NF-kB like factor DIF has weaker effects on Drosophila melanogaster immune defenses than previously thought
    Eric Le Bourg
    Centre de Recherche sur la Cognition Animale, UMR CNRS, Universite Paul Sabatier, Toulouse, France
    J Comp Physiol B 181:741-50. 2011
    ..the drosomycin and metchnikowin antimicrobial peptide genes by inducing the translocation into the nucleus of the DIF transcription factor...
  60. pmc Virus recognition by Toll-7 activates antiviral autophagy in Drosophila
    Margaret Nakamoto
    Department of Microbiology, Penn Genome Frontiers Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Immunity 36:658-67. 2012
    ....
  61. pmc Polydnavirus Ank proteins bind NF-κB homodimers and inhibit processing of Relish
    Kavita Bitra
    Department of Entomology, University of Georgia, Athens, Georgia, USA
    PLoS Pathog 8:e1002722. 2012
    ..Surface plasmon resonance (SPR) and co-immunoprecipitation assays showed that the IκB Cactus from Drosophila bound Dif and Dorsal homodimers more strongly than Relish homodimers...
  62. doi The NF-κB-like factor DIF could explain some positive effects of a mild stress on longevity, behavioral aging, and resistance to strong stresses in Drosophila melanogaster
    Eric Le Bourg
    Centre de Recherche sur la Cognition Animale, Universite Paul Sabatier, UMR CNRS 5169, 118 route de Narbonne, 31062, Toulouse Cedex 9, France
    Biogerontology 13:445-55. 2012
    ..In order to know whether these effects could be explained by the DIF transcription factor (a NF-κB-like factor in the Toll innate immunity pathway), the Dif ( 1 ) mutant and its ..
  63. ncbi Dif and cactus are colocalized in the larval nervous system of Drosophila melanogaster
    R Cantera
    Department of Zoology, University of Stockholm, Sweden
    J Neurobiol 38:16-26. 1999
    The Rel protein Dif is a transcription factor suggested to control part of the immune response in the fruit fly Drosophila melanogaster...
  64. ncbi Relish, a central factor in the control of humoral but not cellular immunity in Drosophila
    M Hedengren
    Umeå Center for Molecular Pathogenesis, Umea University, Sweden
    Mol Cell 4:827-37. 1999
    ..Our results illustrate the importance of the humoral response in Drosophila immunity and demonstrate that Relish plays a key role in this response...
  65. ncbi AP-1, but not NF-kappa B, is required for efficient steroid-triggered cell death in Drosophila
    M Lehmann
    Howard Hughes Medical Institute, Department of Human Genetics, 15 North 2030 East Room 5100, University of Utah, Utah, UT 84112 5331, USA
    Cell Death Differ 9:581-90. 2002
    ..of the three Drosophila Rel/NF-kappa B genes are expressed in doomed salivary glands and that one family member, Dif, is induced in a stage-specific manner immediately before the onset of programmed cell death...
  66. ncbi The lesswright mutation activates Rel-related proteins, leading to overproduction of larval hemocytes in Drosophila melanogaster
    Liang Huang
    Department of Biological Sciences and Molecular and Cell Biology Program, Ohio University, Athens, 45701, USA
    Dev Biol 280:407-20. 2005
    ..Dl) protein in the nucleus were observed in lwr mutant hemocytes, and the dl and Dorsal-related immunity factor (Dif) mutations were found to be suppressors of the lwr mutation...
  67. pmc An essential complementary role of NF-kappaB pathway to microbicidal oxidants in Drosophila gut immunity
    Ji Hwan Ryu
    Division of Molecular Life Science and National Creative Research Initiative Center for Symbiosystem, Ewha Woman s University, Seoul, South Korea
    EMBO J 25:3693-701. 2006
    ..This system provides the Drosophila gut immunity the versatility necessary to manage sporadic invasion of virulent pathogens that somehow counteract or evade the ROS-dependent immunity...
  68. ncbi The maternal NF-kappaB/dorsal gradient of Tribolium castaneum: dynamics of early dorsoventral patterning in a short-germ beetle
    G Chen
    Max Planck Institut fur Entwicklungsbiologie, Spemannstrasse 35 II, D 72076 Tubingen, Germany
    Development 127:5145-56. 2000
    ..However, Dorsal is up-regulated and transiently forms a nuclear gradient in the serosa, a protective extraembryonic cell layer ultimately covering the whole embryo...
  69. pmc Requirements of peptidoglycan structure that allow detection by the Drosophila Toll pathway
    Sergio R Filipe
    Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
    EMBO Rep 6:327-33. 2005
    ..We suggest a model whereby GNBP1 is involved in the hydrolysis of Gram-positive peptidoglycan producing new glycan reducing ends, which are subsequently detected by PGRP-SA...
  70. ncbi A role for Hemolectin in coagulation and immunity in Drosophila melanogaster
    Christine Lesch
    Department of Molecular Biology and Functional Genomics, University of Stockholm, Svante Arrhenius Väg 16 18, 10691 Stockholm, Sweden
    Dev Comp Immunol 31:1255-63. 2007
    ..This demonstrates an immunological role of this clotting protein and reinforces the importance of the clot in insect immunity...
  71. pmc Specificity of Rel-inhibitor interactions in Drosophila embryos
    K Tatei
    Department of Biology, University of California, San Diego, La Jolla 92093 0347, USA
    Mol Cell Biol 15:3627-34. 1995
    ..Recent crystallographic studies suggest that the region I sequence and the nuclear localization sequence might form a composite surface which interacts with inhibitor proteins...
  72. ncbi Molecular genetics of Drosophila immunity
    Y T Ip
    Department of Biology, University of California San Diego, La Jolla 92093 0322
    Curr Opin Genet Dev 4:672-7. 1994
    ..Recent studies suggest that the induction of the humoral response involves Rel-containing regulatory proteins, Dif and dorsal, which are related to mammalian NF-kappa B...
  73. ncbi Differential induction of antibacterial transcripts in Drosophila susceptible and resistant to parasitism by Leptopilina boulardi
    C Coustau
    Department of Entomology, University of Wisconsin Madison, Russell Laboratories, USA
    Insect Mol Biol 5:167-72. 1996
    ..to study the expression of three genes involved in the antibacterial response: Dorsal-related immunity factor (Dif), Cecropin (CecA1) and Diptericin (Dip)...
  74. ncbi The coevolution of gene family trees
    K J Fryxell
    Department of Biology, University of California, Riverside 92521, USA
    Trends Genet 12:364-9. 1996
    ..These correlations suggest that the family trees of functionally related gene families co-evolved because functionally complementary gene duplication and divergence events tended to be retained by natural selection...
  75. ncbi A conserved signaling pathway: the Drosophila toll-dorsal pathway
    M P Belvin
    Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA
    Annu Rev Cell Dev Biol 12:393-416. 1996
    ....
  76. pmc Adjacent GATA and kappa B-like motifs regulate the expression of a Drosophila immune gene
    L Kadalayil
    Department of Molecular Biology, Arrhenius Laboratories for Natural Sciences, Stockholm University, S 106 91, Sweden
    Nucleic Acids Res 25:1233-9. 1997
    ..that the Drosophila Rel protein which binds to the kappaB-like site requires an intact GATA site for maximal Dif-mediated transactivation of the Cecropin A1 gene...
  77. ncbi Signalling pathways: a common theme in plants and animals?
    I Wilson
    Carnegie Institution of Washington, Department of Plant Biology, 290 Panama Street, Stanford, California 94305, USA
    Curr Biol 7:R175-8. 1997
    ..The unexpected notion that disease resistance mechanisms may use similar regulatory pathways to developmental processes has emerged from recent advances in understanding signal transduction pathways in insects, mammals and plants...
  78. pmc The 18-wheeler mutation reveals complex antibacterial gene regulation in Drosophila host defense
    M J Williams
    Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556 5645, USA
    EMBO J 16:6120-30. 1997
    ..Nuclear translocation of the Rel protein Dorsal-like immunity factor (Dif) is inhibited, though nuclear translocation of another Rel protein, Dorsal, is unaffected...
  79. ncbi Related signaling networks in Drosophila that control dorsoventral patterning in the embryo and the immune response
    L P Wu
    Molecular Biology Program, Sloan Kettering Institute, New York, New York 10021, USA
    Cold Spring Harb Symp Quant Biol 62:97-103. 1997
  80. pmc Genetic control of development of the mushroom bodies, the associative learning centers in the Drosophila brain, by the eyeless, twin of eyeless, and Dachshund genes
    M Kurusu
    Institute of Biological Sciences, University of Tsukuba, Tsukuba 305 8572, Japan
    Proc Natl Acad Sci U S A 97:2140-4. 2000
    ..These data argue for a distinct combinatorial code of regulatory genes for MBs as compared with eye development and suggest conserved roles of Pax6 homologs in the genetic programs of the olfactory learning centers of complex brains...
  81. ncbi Cytotoxicity and cytotoxic molecules in invertebrates
    A J Nappi
    Department of Biology, Loyola University, Chicago, IL 60626, USA
    Bioessays 22:469-80. 2000
    ..The signal transduction pathways that are involved in mediating the production of these substances appear to be very similar among animal species, suggesting a common ancestral origin for the innate immune systems...
  82. ncbi Developmental biology. Post-expressionist flies
    S Bray
    Nature 407:314-5. 2000
  83. pmc The Drosophila atypical protein kinase C-ref(2)p complex constitutes a conserved module for signaling in the toll pathway
    Antonia Avila
    Centro de Biologia Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas, Universidad Autonoma, Canto Blanco, 28049 Madrid, Spain
    Mol Cell Biol 22:8787-95. 2002
    ..DaPKC) is required for the stimulation of the Toll-signaling pathway, which activates the NF-kappaB homologues Dif and Dorsal...
  84. ncbi Drosophila innate immunity: a genomic view of pathogen defense
    Heinrich Jasper
    Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY 14642, USA
    Mol Cell 10:967-9. 2002
  85. ncbi Flies kNOw how to signal
    Neal Silverman
    Department of Medicine, University of Massachusetts Medical School, 364 Plantation Road, Worcester, MA 01605, USA
    Dev Cell 4:5-6. 2003
    ..NO-mediated signaling was implicated in the communication between the site of a localized infection and the major immune organ of the fly, the fat body...
  86. ncbi Tamo selectively modulates nuclear import in Drosophila
    Svetlana Minakhina
    Waksman Institute, Department of Molecular Biology and Biochemistry, NJ Cancer Center, Rutgers University, 190 Frelinghuysen Road, Piscataway, NJ 08854 8020, USA
    Genes Cells 8:299-310. 2003
    ..An important aspect of all NF-kappaB/Rel pathways is the translocation of the Rel proteins from the cytoplasm to the nucleus, where they function as transcription factors...
  87. ncbi Genetic basis of natural variation in D. melanogaster antibacterial immunity
    Brian P Lazzaro
    Department of Entomology, 4138 Comstock Hall, Cornell University, Ithaca, NY 14853, USA
    Science 303:1873-6. 2004
    ..Variation in these genes, therefore, seems to drive variability in immunocompetence among wild Drosophila...
  88. pmc Innate immunity in fruit flies: a textbook example of genomic recycling
    Shubha Govind
    Department of Biology and The Graduate Center, City College of New York, New York, New York, USA
    PLoS Biol 2:E276. 2004
  89. pmc Ligand-induced dimerization of Drosophila peptidoglycan recognition proteins in vitro
    Peter Mellroth
    Department of Genetics, Microbiology, and Toxicology, University of Stockholm, S 106 91 Stockholm, Sweden
    Proc Natl Acad Sci U S A 102:6455-60. 2005
    ..and PGRP-LCx are bona fide pattern recognition receptors, and PGRP-SA, the peptidoglycan receptor of the Toll/Dif pathway, has selective affinity for different peptidoglycans...
  90. ncbi Drosophila innate immunity goes viral
    Y Tony Ip
    Nat Immunol 6:863-4. 2005
  91. ncbi Weckle is a zinc finger adaptor of the toll pathway in dorsoventral patterning of the Drosophila embryo
    Li ying Chen
    Department of Life Science, Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan 30034, Republic of China
    Curr Biol 16:1183-93. 2006
    ..degradation of the inhibitor Cactus, thus allowing the nuclear translocation of the transcription factor Dorsal/Dif. weckle (wek) was previously identified as a new dorsal group gene that encodes a putative zinc finger ..
  92. pmc IKK epsilon signaling: not just NF-kappaB
    Andreas Bergmann
    The University of Texas MD Anderson Cancer Center, Department of Biochemistry and Molecular Biology, 1515 Holcombe Blvd Unit 1000, Houston, Texas 77030, USA
    Curr Biol 16:R588-90. 2006
    ..Surprisingly, three recent reports implicate IKKs in Drosophila in seemingly unrelated functions, including non-apoptotic caspase activation and cytoskeleton organization...
  93. ncbi The nucleoporin Nup214 sequesters CRM1 at the nuclear rim and modulates NFkappaB activation in Drosophila
    Nikos Xylourgidis
    Department of Developmental Biology, Wenner Gren Institute, Stockholm University, S 10691, Stockholm, Sweden
    J Cell Sci 119:4409-19. 2006
    ..We hypothesize that variation in levels of the Nup214-Nup88 complex at the pore changes the amount of NPC-bound CRM1 and influences the relative strength and duration of NFkappaB signaling responses...
  94. pmc GATA factors participate in tissue-specific immune responses in Drosophila larvae
    Kate Senger
    Department of Molecular and Cell Biology, Division of Genetics, Genomics, and Development, Center for Integrative Genomics, University of California, Berkeley, CA 94720 3204, USA
    Proc Natl Acad Sci U S A 103:15957-62. 2006
    ..Based on this evidence we propose that dGATAe mediates a Toll-independent immune response in the midgut, providing a window into the first and perhaps most ancient line of animal defense...
  95. ncbi Isolation of regulators of Drosophila immune defense genes by a double interaction screen in yeast
    Anna Junell
    Department of Molecular Biology and Functional Genomics, Stockholm University, S 109 61 Stockholm, Sweden
    Insect Biochem Mol Biol 37:202-12. 2007
    ..performed a double interaction screen in yeast to isolate Drosophila cDNAs coding for direct regulators, as well as Dif co-regulators, of the CecropinA1 gene...
  96. pmc Functional conservation of Rel binding sites in drosophilid genomes
    Richard R Copley
    Wellcome Trust Centre for Human Genetics, Oxford University, Oxford OX3 7BN, United Kingdom
    Genome Res 17:1327-35. 2007
    ..Using molecular modeling we compare tertiary structures of the Drosophila Rel family proteins Dorsal, Dif, and Relish and demonstrate that their DNA-binding and protein dimerization domains undergo distinct rates of ..
  97. pmc Autophagic control of listeria through intracellular innate immune recognition in drosophila
    Tamaki Yano
    Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980 8578, Japan
    Nat Immunol 9:908-16. 2008
    ..Autophagy induction occurred independently of the Toll and IMD innate signaling pathways. Our findings define a pathway leading from the intracellular pattern-recognition receptors to the induction of autophagy to host defense...
  98. pmc The Toll-->NFkappaB signaling pathway mediates the neuropathological effects of the human Alzheimer's Abeta42 polypeptide in Drosophila
    Lihua Tan
    Department of Molecular Biology, Princeton University, Princeton, New Jersey, USA
    PLoS ONE 3:e3966. 2008
    ....
  99. pmc Tube Is an IRAK-4 homolog in a Toll pathway adapted for development and immunity
    Par Towb
    Division of Biological Sciences, University of California at San Diego, La Jolla, CA 92093 0349, USA
    J Innate Immun 1:309-21. 2009
    ..Together, these studies reveal previously unrecognized parallels in Toll signaling in fly and human innate immunity and shed light on the evolution of pathway organization and function...
  100. pmc Cooperative regulation of the induction of the novel antibacterial Listericin by peptidoglycan recognition protein LE and the JAK-STAT pathway
    Akira Goto
    Graduate School of Pharmaceutical Science, Tohoku University, Sendai 980 8578, Japan
    J Biol Chem 285:15731-8. 2010
    ..Based on these findings, we propose that the Listericin gene encodes a novel antibacterial peptide-like protein whose induction is cooperatively regulated by PGRP-LE and the JAK-STAT pathway...
  101. pmc The dorsal-related immunity factor, Dif, is a sequence-specific trans-activator of Drosophila Cecropin gene expression
    U M Petersen
    Department of Molecular Biology, Arrhenius Laboratories for Natural Sciences, Stockholm University, Sweden
    EMBO J 14:3146-58. 1995
    A new member of the Rel family of transcription factors, the dorsal-related immunity factor, Dif, was recently cloned and suggested to be involved in regulating the immune response in Drosophila...

Research Grants2

  1. Evolutionary Genomics of Anti-Malaria Genes in Mosquito
    Brian P Lazzaro; Fiscal Year: 2010
    ..Evolutionary patterns in mosquito defense genes will be used to identify proteins that coevolve with malaria parasites. This work may suggest genetic targets that could be manipulated to limit malaria transmission. ..
  2. TOLL RECEPTORS AND CONTROL OF MAMMALIAN IMMUNITY
    Ruslan Medzhitov; Fiscal Year: 2005
    ..Our ultimate goal is to understand whether activation of different TLRs results in the induction of distinct cellular and immune responses. ..