Dif

Summary

Gene Symbol: Dif
Description: Dorsal-related immunity factor
Alias: 6794, CG6794, DIF, Dmel\CG6794, dif, Dorsal-related immunity factor, 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
Products:     Dif

Top Publications

  1. Ayyar S, Pistillo D, Calleja M, Brookfield A, Gittins K, Goldstone C, et al. NF-kappaB/Rel-mediated regulation of the neural fate in Drosophila. PLoS ONE. 2007;2:e1178 pubmed
    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...
  2. Ha E, Oh C, Ryu J, Bae Y, Kang S, Jang I, et al. An antioxidant system required for host protection against gut infection in Drosophila. Dev Cell. 2005;8:125-32 pubmed
    ..These results imply that homeostasis of redox balance by IRC is one of the most critical factors affecting host survival during continuous host-microbe interaction in the gastrointestinal tract. ..
  3. Hedengren M, Asling B, Dushay M, Ando I, Ekengren S, Wihlborg M, et al. Relish, a central factor in the control of humoral but not cellular immunity in Drosophila. Mol Cell. 1999;4:827-37 pubmed
    ..Our results illustrate the importance of the humoral response in Drosophila immunity and demonstrate that Relish plays a key role in this response. ..
  4. Paddibhatla I, Lee M, Kalamarz M, Ferrarese R, Govind S. Role for sumoylation in systemic inflammation and immune homeostasis in Drosophila larvae. PLoS Pathog. 2010;6:e1001234 pubmed publisher
  5. Kim M, Lee J, Lee S, Kim E, Chung J. Caspar, a suppressor of antibacterial immunity in Drosophila. Proc Natl Acad Sci U S A. 2006;103:16358-63 pubmed
    ..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. ..
  6. Cornwell W, Kirkpatrick R. Cactus-independent nuclear translocation of Drosophila RELISH. J Cell Biochem. 2001;82:22-37 pubmed
  7. Agaisse H, Perrimon N. The roles of JAK/STAT signaling in Drosophila immune responses. Immunol Rev. 2004;198:72-82 pubmed
  8. Tanji T, Yun E, Ip Y. Heterodimers of NF-kappaB transcription factors DIF and Relish regulate antimicrobial peptide genes in Drosophila. Proc Natl Acad Sci U S A. 2010;107:14715-20 pubmed publisher
    ..Dorsal and DIF act downstream of Toll, whereas Relish acts downstream of IMD to regulate target gene expression...
  9. Bettencourt R, Asha H, Dearolf C, Ip Y. Hemolymph-dependent and -independent responses in Drosophila immune tissue. J Cell Biochem. 2004;92:849-63 pubmed
    ..Using GFP-Dorsal, -Dif, and -Relish reporter proteins in ex vivo assays, we demonstrate that Drosophila fat bodies, a major immune tissue, ..

More Information

Publications67

  1. Han Z, Ip Y. Interaction and specificity of Rel-related proteins in regulating Drosophila immunity gene expression. J Biol Chem. 1999;274:21355-61 pubmed
    ..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 ..
  2. Wang Z, Flax L, Kemp M, Linhardt R, Baron M. Host and pathogen glycosaminoglycan-binding proteins modulate antimicrobial peptide responses in Drosophila melanogaster. Infect Immun. 2011;79:606-16 pubmed publisher
  3. Cha G, Cho K, Lee J, Kim M, Kim E, Park J, et al. Discrete functions of TRAF1 and TRAF2 in Drosophila melanogaster mediated by c-Jun N-terminal kinase and NF-kappaB-dependent signaling pathways. Mol Cell Biol. 2003;23:7982-91 pubmed
    ..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-..
  4. Ligoxygakis P, Pelte N, Hoffmann J, Reichhart J. Activation of Drosophila Toll during fungal infection by a blood serine protease. Science. 2002;297:114-6 pubmed
    ..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. ..
  5. Matskevich A, Quintin J, Ferrandon D. The Drosophila PRR GNBP3 assembles effector complexes involved in antifungal defenses independently of its Toll-pathway activation function. Eur J Immunol. 2010;40:1244-54 pubmed publisher
    ..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. ..
  6. Matova N, Anderson K. Rel/NF-kappaB double mutants reveal that cellular immunity is central to Drosophila host defense. Proc Natl Acad Sci U S A. 2006;103:16424-9 pubmed
    ..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...
  7. Uvell H, Engstrom Y. Functional characterization of a novel promoter element required for an innate immune response in Drosophila. Mol Cell Biol. 2003;23:8272-81 pubmed
    ..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...
  8. Mace K, Pearson J, McGinnis W. An epidermal barrier wound repair pathway in Drosophila is mediated by grainy head. Science. 2005;308:381-5 pubmed publisher
    ..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...
  9. Qiu P, Pan P, Govind S. A role for the Drosophila Toll/Cactus pathway in larval hematopoiesis. Development. 1998;125:1909-20 pubmed
    ..These findings are discussed in light of similar hematopoietic functions of Rel/I(kappa)B-family proteins in mice. ..
  10. Meister M, Lemaitre B, Hoffmann J. Antimicrobial peptide defense in Drosophila. Bioessays. 1997;19:1019-26 pubmed
    ..Recent data on the molecular mechanisms underlying recognition of non-self are also discussed in this review. ..
  11. Senger K, Armstrong G, Rowell W, Kwan J, Markstein M, Levine M. Immunity regulatory DNAs share common organizational features in Drosophila. Mol Cell. 2004;13:19-32 pubmed
    ..Two classes of transcription factors have been implicated in this process: the REL-containing proteins, Dorsal, Dif, and Relish, and the GATA factor Serpent...
  12. Avadhanula V, Weasner B, Hardy G, Kumar J, Hardy R. A novel system for the launch of alphavirus RNA synthesis reveals a role for the Imd pathway in arthropod antiviral response. PLoS Pathog. 2009;5:e1000582 pubmed publisher
    ..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. ..
  13. Stein D, Goltz J, Jurcsak J, Stevens L. The Dorsal-related immunity factor (Dif) can define the dorsal-ventral axis of polarity in the Drosophila embryo. Development. 1998;125:2159-69 pubmed
    ..b>Dif, a more recently identified Drosophila Rel-homologue, has been proposed to act as a mediator of the immune response ..
  14. Hallem E, Rengarajan M, Ciche T, Sternberg P. Nematodes, bacteria, and flies: a tripartite model for nematode parasitism. Curr Biol. 2007;17:898-904 pubmed
  15. Choe K, Werner T, Stoven S, Hultmark D, Anderson K. Requirement for a peptidoglycan recognition protein (PGRP) in Relish activation and antibacterial immune responses in Drosophila. Science. 2002;296:359-62 pubmed
  16. Rutschmann S, Kilinc A, Ferrandon D. Cutting edge: the toll pathway is required for resistance to gram-positive bacterial infections in Drosophila. J Immunol. 2002;168:1542-6 pubmed
    ..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...
  17. Rutschmann S, Jung A, Hetru C, Reichhart J, Hoffmann J, Ferrandon D. The Rel protein DIF mediates the antifungal but not the antibacterial host defense in Drosophila. Immunity. 2000;12:569-80 pubmed
    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...
  18. Bischoff V, Vignal C, Boneca I, Michel T, Hoffmann J, Royet J. Function of the drosophila pattern-recognition receptor PGRP-SD in the detection of Gram-positive bacteria. Nat Immunol. 2004;5:1175-80 pubmed
    ..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. ..
  19. Bitra K, Suderman R, Strand M. Polydnavirus Ank proteins bind NF-?B homodimers and inhibit processing of Relish. PLoS Pathog. 2012;8:e1002722 pubmed publisher
    ..Surface plasmon resonance (SPR) and co-immunoprecipitation assays showed that the I?B Cactus from Drosophila bound Dif and Dorsal homodimers more strongly than Relish homodimers...
  20. DiAngelo J, Bland M, Bambina S, Cherry S, Birnbaum M. The immune response attenuates growth and nutrient storage in Drosophila by reducing insulin signaling. Proc Natl Acad Sci U S A. 2009;106:20853-8 pubmed publisher
    ..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...
  21. Matova N, Anderson K. Drosophila Rel proteins are central regulators of a robust, multi-organ immune network. J Cell Sci. 2010;123:627-33 pubmed publisher
    ..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 ..
  22. Manfruelli P, Reichhart J, Steward R, Hoffmann J, Lemaitre B. A mosaic analysis in Drosophila fat body cells of the control of antimicrobial peptide genes by the Rel proteins Dorsal and DIF. EMBO J. 1999;18:3380-91 pubmed
    ..The Rel proteins Dorsal and DIF (Dorsal-related immunity factor) are possible candidates for the transactivating protein in the Toll pathway that ..
  23. Wu L, Anderson K. Regulated nuclear import of Rel proteins in the Drosophila immune response. Nature. 1998;392:93-7 pubmed
    ..In response to infection, two Rel proteins, Dif and Dorsal, translocate from the cytoplasm to the nuclei of larval fat-body cells...
  24. Hoffmann J. The immune response of Drosophila. Nature. 2003;426:33-8 pubmed
    ..Recent progress in research on Drosophila immune defence provides evidence for similarities and differences between Drosophila immune responses and mammalian innate immunity. ..
  25. Le Bourg E. The NF-kB like factor DIF has weaker effects on Drosophila melanogaster immune defenses than previously thought. J Comp Physiol B. 2011;181:741-50 pubmed publisher
    ..the drosomycin and metchnikowin antimicrobial peptide genes by inducing the translocation into the nucleus of the DIF transcription factor...
  26. Dushay M, Asling B, Hultmark D. Origins of immunity: Relish, a compound Rel-like gene in the antibacterial defense of Drosophila. Proc Natl Acad Sci U S A. 1996;93:10343-7 pubmed
    ..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. ..
  27. Huang L, Ohsako S, Tanda S. The lesswright mutation activates Rel-related proteins, leading to overproduction of larval hemocytes in Drosophila melanogaster. Dev Biol. 2005;280:407-20 pubmed
    ..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...
  28. Tang H, Kambris Z, Lemaitre B, Hashimoto C. Two proteases defining a melanization cascade in the immune system of Drosophila. J Biol Chem. 2006;281:28097-104 pubmed
    ..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. ..
  29. Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell. 2006;124:783-801 pubmed
    ..New insights into innate immunity are changing the way we think about pathogenesis and the treatment of infectious diseases, allergy, and autoimmunity. ..
  30. Leone P, Bischoff V, Kellenberger C, Hetru C, Royet J, Roussel A. Crystal structure of Drosophila PGRP-SD suggests binding to DAP-type but not lysine-type peptidoglycan. Mol Immunol. 2008;45:2521-30 pubmed publisher
    ..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. ..
  31. van Uden P, Kenneth N, Webster R, Müller H, Mudie S, Rocha S. Evolutionary conserved regulation of HIF-1β by NF-κB. PLoS Genet. 2011;7:e1001285 pubmed publisher
    ..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. ..
  32. Le Bourg E, Malod K, Massou I. The NF-?B-like factor DIF could explain some positive effects of a mild stress on longevity, behavioral aging, and resistance to strong stresses in Drosophila melanogaster. Biogerontology. 2012;13:445-55 pubmed publisher
    ..In order to know whether these effects could be explained by the DIF transcription factor (a NF-?B-like factor in the Toll innate immunity pathway), the Dif ( 1 ) mutant and its ..
  33. Ip Y, Reach M, Engstrom Y, Kadalayil L, Cai H, González Crespo S, et al. Dif, a dorsal-related gene that mediates an immune response in Drosophila. Cell. 1993;75:753-63 pubmed
    ..A novel Rel-containing gene in Drosophila, Dif (dorsal-related immunity factor), provides a potential link between these seemingly disparate processes...
  34. Cantera R, Roos E, Engstrom Y. Dif and cactus are colocalized in the larval nervous system of Drosophila melanogaster. J Neurobiol. 1999;38:16-26 pubmed
    The Rel protein Dif is a transcription factor suggested to control part of the immune response in the fruit fly Drosophila melanogaster...
  35. Jung A, Criqui M, Rutschmann S, Hoffmann J, Ferrandon D. Microfluorometer assay to measure the expression of beta-galactosidase and green fluorescent protein reporter genes in single Drosophila flies. Biotechniques. 2001;30:594-8, 600-1 pubmed
    ..This method may be used in any screen that requires the quantification of reporter gene activity in individual insects. ..
  36. Lehming N, McGuire S, Brickman J, Ptashne M. Interactions of a Rel protein with its inhibitor. Proc Natl Acad Sci U S A. 1995;92:10242-6 pubmed
    ..From this and data of others, we identify the likely surface of Dorsal that binds Cactus. We also describe a modified PCR mutagenesis procedure, easier to use than conventional methods, that produces a library of high complexity. ..
  37. Leclerc V, Pelte N, El Chamy L, Martinelli C, Ligoxygakis P, Hoffmann J, et al. Prophenoloxidase activation is not required for survival to microbial infections in Drosophila. EMBO Rep. 2006;7:231-5 pubmed
    ..This raises the question with regard to the precise function of phenoloxidase activation in defence, if any. ..
  38. Wang L, Gilbert R, Atilano M, Filipe S, Gay N, Ligoxygakis P. Peptidoglycan recognition protein-SD provides versatility of receptor formation in Drosophila immunity. Proc Natl Acad Sci U S A. 2008;105:11881-6 pubmed publisher
    ..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. ..
  39. Gobert V, Gottar M, Matskevich A, Rutschmann S, Royet J, Belvin M, et al. Dual activation of the Drosophila toll pathway by two pattern recognition receptors. Science. 2003;302:2126-30 pubmed
    ..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. ..
  40. Brown A, Baumbach J, Cook P, Ligoxygakis P. Short-term starvation of immune deficient Drosophila improves survival to gram-negative bacterial infections. PLoS ONE. 2009;4:e4490 pubmed publisher
    ..Surprisingly, NO signalling required the NF-kappaB protein Dif, usually needed for responses against Gram-positive bacteria...
  41. Meng X, Khanuja B, Ip Y. Toll receptor-mediated Drosophila immune response requires Dif, an NF-kappaB factor. Genes Dev. 1999;13:792-7 pubmed
    The induction of immunity genes in Drosophila has been proposed to be dependent on Dorsal, Dif, and Relish, the NF-kappaB-related factors...
  42. Hoffmann J, Kafatos F, Janeway C, Ezekowitz R. Phylogenetic perspectives in innate immunity. Science. 1999;284:1313-8 pubmed
    ..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. ..
  43. Nehme N, Liegeois S, Kele B, Giammarinaro P, Pradel E, Hoffmann J, et al. A model of bacterial intestinal infections in Drosophila melanogaster. PLoS Pathog. 2007;3:e173 pubmed
    ..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...
  44. Hedengren Olcott M, Olcott M, Mooney D, Ekengren S, Geller B, Taylor B. Differential activation of the NF-kappaB-like factors Relish and Dif in Drosophila melanogaster by fungi and Gram-positive bacteria. J Biol Chem. 2004;279:21121-7 pubmed
    ..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...
  45. Zambon R, Nandakumar M, Vakharia V, Wu L. The Toll pathway is important for an antiviral response in Drosophila. Proc Natl Acad Sci U S A. 2005;102:7257-62 pubmed
    ..Additionally, our results demonstrate the validity of using a genetic approach to identify genes and pathways used in viral innate immune responses in Drosophila...
  46. Sabatier L, Jouanguy E, Dostert C, Zachary D, Dimarcq J, Bulet P, et al. Pherokine-2 and -3. Eur J Biochem. 2003;270:3398-407 pubmed
    ..Both Phk-2 and Phk-3 are strongly expressed during metamorphosis, suggesting that they may participate in tissue-remodeling. ..
  47. Tsichritzis T, Gaentzsch P, Kosmidis S, Brown A, SKOULAKIS E, Ligoxygakis P, et al. A Drosophila ortholog of the human cylindromatosis tumor suppressor gene regulates triglyceride content and antibacterial defense. Development. 2007;134:2605-14 pubmed
    ..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. ..
  48. Kambris Z, Brun S, Jang I, Nam H, Romeo Y, Takahashi K, et al. Drosophila immunity: a large-scale in vivo RNAi screen identifies five serine proteases required for Toll activation. Curr Biol. 2006;16:808-13 pubmed
    ..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. ..
  49. Gottar M, Gobert V, Michel T, Belvin M, Duyk G, Hoffmann J, et al. The Drosophila immune response against Gram-negative bacteria is mediated by a peptidoglycan recognition protein. Nature. 2002;416:640-4 pubmed
    ..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. ..
  50. Michel T, Reichhart J, Hoffmann J, Royet J. Drosophila Toll is activated by Gram-positive bacteria through a circulating peptidoglycan recognition protein. Nature. 2001;414:756-9 pubmed
    ..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...
  51. Rutschmann S, Jung A, Zhou R, Silverman N, Hoffmann J, Ferrandon D. Role of Drosophila IKK gamma in a toll-independent antibacterial immune response. Nat Immunol. 2000;1:342-7 pubmed
    ..However, it is not required for the Toll-DIF-dependent antifungal host defense...
  52. Chiu H, Ring B, Sorrentino R, Kalamarz M, Garza D, Govind S. dUbc9 negatively regulates the Toll-NF-kappa B pathways in larval hematopoiesis and drosomycin activation in Drosophila. Dev Biol. 2005;288:60-72 pubmed
    ..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...
  53. Ryu J, Ha E, Oh C, Seol J, Brey P, Jin I, et al. An essential complementary role of NF-kappaB pathway to microbicidal oxidants in Drosophila gut immunity. EMBO J. 2006;25:3693-701 pubmed
    ..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. ..
  54. Ligoxygakis P, Pelte N, Ji C, Leclerc V, Duvic B, Belvin M, et al. A serpin mutant links Toll activation to melanization in the host defence of Drosophila. EMBO J. 2002;21:6330-7 pubmed
    ..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. ..
  55. Ligoxygakis P, Bulet P, Reichhart J. Critical evaluation of the role of the Toll-like receptor 18-Wheeler in the host defense of Drosophila. EMBO Rep. 2002;3:666-73 pubmed
    ..18-Wheeler does not qualify as a pattern recognition receptor of Gram-negative bacteria. ..
  56. Tanji T, Hu X, Weber A, Ip Y. Toll and IMD pathways synergistically activate an innate immune response in Drosophila melanogaster. Mol Cell Biol. 2007;27:4578-88 pubmed
    ..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. ..
  57. Gottar M, Gobert V, Matskevich A, Reichhart J, Wang C, Butt T, et al. Dual detection of fungal infections in Drosophila via recognition of glucans and sensing of virulence factors. Cell. 2006;127:1425-37 pubmed
    ..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. ..
  58. Nakamoto M, Moy R, Xu J, Bambina S, Yasunaga A, Shelly S, et al. Virus recognition by Toll-7 activates antiviral autophagy in Drosophila. Immunity. 2012;36:658-67 pubmed publisher