Skip to main content
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1996 Apr 1;24(7):1238–1245. doi: 10.1093/nar/24.7.1238

Drosophila immunity: a comparative analysis of the Rel proteins dorsal and Dif in the induction of the genes encoding diptericin and cecropin.

I Gross 1, P Georgel 1, C Kappler 1, J M Reichhart 1, J A Hoffmann 1
PMCID: PMC145794  PMID: 8614625

Abstract

In Drosophila, bacterial challenge induces the rapid transcription of several genes encoding potent antibacterial peptides. The upstream sequences of the diptericin and cecropin Al genes, which have been investigated in detail, contain two, respectively one sequence element homologous to the binding site of the mammalian nuclear factor kappaB. These elements have been shown to be mandatory for immune-induced transcription of both genes. Functional studies have shown that these kappaB-related elements can be the target for the Drosophila Rel proteins dorsal and Dif. Here we present a comparative analysis of the transactivating capacities of these proteins on reporter genes fused to either the diptericin or the cecropin kappaB-related motifs. We conclude from our results: (i) the kappaB motifs of the diptericin and cecropin genes are not functionally equivalent; (ii) the dorsal and Dif proteins have distinct DNA-binding characteristics; (iii) dorsal and Dif can heterodimerize in vitro; (iv) mutants containing no copies of dorsal and a single copy of Dif retain their full capacity to express the diptericin and cecropin genes in response to challenge.

Full Text

The Full Text of this article is available as a PDF (163.1 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Engström Y., Kadalayil L., Sun S. C., Samakovlis C., Hultmark D., Faye I. kappa B-like motifs regulate the induction of immune genes in Drosophila. J Mol Biol. 1993 Jul 20;232(2):327–333. doi: 10.1006/jmbi.1993.1392. [DOI] [PubMed] [Google Scholar]
  2. Gateff E. Malignant neoplasms of genetic origin in Drosophila melanogaster. Science. 1978 Jun 30;200(4349):1448–1459. doi: 10.1126/science.96525. [DOI] [PubMed] [Google Scholar]
  3. Georgel P., Kappler C., Langley E., Gross I., Nicolas E., Reichhart J. M., Hoffmann J. A. Drosophila immunity. A sequence homologous to mammalian interferon consensus response element enhances the activity of the diptericin promoter. Nucleic Acids Res. 1995 Apr 11;23(7):1140–1145. doi: 10.1093/nar/23.7.1140. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Georgel P., Meister M., Kappler C., Lemaitre B., Reichhart J. M., Hoffmann J. A. Insect immunity: the diptericin promoter contains multiple functional regulatory sequences homologous to mammalian acute-phase response elements. Biochem Biophys Res Commun. 1993 Dec 15;197(2):508–517. doi: 10.1006/bbrc.1993.2508. [DOI] [PubMed] [Google Scholar]
  5. Grilli M., Chiu J. J., Lenardo M. J. NF-kappa B and Rel: participants in a multiform transcriptional regulatory system. Int Rev Cytol. 1993;143:1–62. doi: 10.1016/s0074-7696(08)61873-2. [DOI] [PubMed] [Google Scholar]
  6. Hoffmann J. A. Innate immunity of insects. Curr Opin Immunol. 1995 Feb;7(1):4–10. doi: 10.1016/0952-7915(95)80022-0. [DOI] [PubMed] [Google Scholar]
  7. Hultmark D. Immune reactions in Drosophila and other insects: a model for innate immunity. Trends Genet. 1993 May;9(5):178–183. doi: 10.1016/0168-9525(93)90165-e. [DOI] [PubMed] [Google Scholar]
  8. Ip Y. T., Kraut R., Levine M., Rushlow C. A. The dorsal morphogen is a sequence-specific DNA-binding protein that interacts with a long-range repression element in Drosophila. Cell. 1991 Jan 25;64(2):439–446. doi: 10.1016/0092-8674(91)90651-e. [DOI] [PubMed] [Google Scholar]
  9. Ip Y. T., Levine M. Molecular genetics of Drosophila immunity. Curr Opin Genet Dev. 1994 Oct;4(5):672–677. doi: 10.1016/0959-437x(94)90133-n. [DOI] [PubMed] [Google Scholar]
  10. Ip Y. T., Park R. E., Kosman D., Bier E., Levine M. The dorsal gradient morphogen regulates stripes of rhomboid expression in the presumptive neuroectoderm of the Drosophila embryo. Genes Dev. 1992 Sep;6(9):1728–1739. doi: 10.1101/gad.6.9.1728. [DOI] [PubMed] [Google Scholar]
  11. Ip Y. T., Reach M., Engstrom Y., Kadalayil L., Cai H., González-Crespo S., Tatei K., Levine M. Dif, a dorsal-related gene that mediates an immune response in Drosophila. Cell. 1993 Nov 19;75(4):753–763. doi: 10.1016/0092-8674(93)90495-c. [DOI] [PubMed] [Google Scholar]
  12. Isoda K., Roth S., Nüsslein-Volhard C. The functional domains of the Drosophila morphogen dorsal: evidence from the analysis of mutants. Genes Dev. 1992 Apr;6(4):619–630. doi: 10.1101/gad.6.4.619. [DOI] [PubMed] [Google Scholar]
  13. Isshiki H., Akira S., Sugita T., Nishio Y., Hashimoto S., Pawlowski T., Suematsu S., Kishimoto T. Reciprocal expression of NF-IL6 and C/EBP in hepatocytes: possible involvement of NF-IL6 in acute phase protein gene expression. New Biol. 1991 Jan;3(1):63–70. [PubMed] [Google Scholar]
  14. Kappler C., Meister M., Lagueux M., Gateff E., Hoffmann J. A., Reichhart J. M. Insect immunity. Two 17 bp repeats nesting a kappa B-related sequence confer inducibility to the diptericin gene and bind a polypeptide in bacteria-challenged Drosophila. EMBO J. 1993 Apr;12(4):1561–1568. doi: 10.1002/j.1460-2075.1993.tb05800.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kopp E. B., Ghosh S. NF-kappa B and rel proteins in innate immunity. Adv Immunol. 1995;58:1–27. doi: 10.1016/s0065-2776(08)60618-5. [DOI] [PubMed] [Google Scholar]
  16. Krasnow M. A., Saffman E. E., Kornfeld K., Hogness D. S. Transcriptional activation and repression by Ultrabithorax proteins in cultured Drosophila cells. Cell. 1989 Jun 16;57(6):1031–1043. doi: 10.1016/0092-8674(89)90341-3. [DOI] [PubMed] [Google Scholar]
  17. Lemaitre B., Meister M., Govind S., Georgel P., Steward R., Reichhart J. M., Hoffmann J. A. Functional analysis and regulation of nuclear import of dorsal during the immune response in Drosophila. EMBO J. 1995 Feb 1;14(3):536–545. doi: 10.1002/j.1460-2075.1995.tb07029.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Meister M., Braun A., Kappler C., Reichhart J. M., Hoffmann J. A. Insect immunity. A transgenic analysis in Drosophila defines several functional domains in the diptericin promoter. EMBO J. 1994 Dec 15;13(24):5958–5966. doi: 10.1002/j.1460-2075.1994.tb06941.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Nelson N., Marks M. S., Driggers P. H., Ozato K. Interferon consensus sequence-binding protein, a member of the interferon regulatory factor family, suppresses interferon-induced gene transcription. Mol Cell Biol. 1993 Jan;13(1):588–599. doi: 10.1128/mcb.13.1.588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Petersen U. M., Björklund G., Ip Y. T., Engström Y. The dorsal-related immunity factor, Dif, is a sequence-specific trans-activator of Drosophila Cecropin gene expression. EMBO J. 1995 Jul 3;14(13):3146–3158. doi: 10.1002/j.1460-2075.1995.tb07317.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Raj N. B., Engelhardt J., Au W. C., Levy D. E., Pitha P. M. Virus infection and interferon can activate gene expression through a single synthetic element, but endogenous genes show distinct regulation. J Biol Chem. 1989 Oct 5;264(28):16658–16666. [PubMed] [Google Scholar]
  22. Reichhart J. M., Meister M., Dimarcq J. L., Zachary D., Hoffmann D., Ruiz C., Richards G., Hoffmann J. A. Insect immunity: developmental and inducible activity of the Drosophila diptericin promoter. EMBO J. 1992 Apr;11(4):1469–1477. doi: 10.1002/j.1460-2075.1992.tb05191.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Samakovlis C., Asling B., Boman H. G., Gateff E., Hultmark D. In vitro induction of cecropin genes--an immune response in a Drosophila blood cell line. Biochem Biophys Res Commun. 1992 Nov 16;188(3):1169–1175. doi: 10.1016/0006-291x(92)91354-s. [DOI] [PubMed] [Google Scholar]
  24. Steward R. Dorsal, an embryonic polarity gene in Drosophila, is homologous to the vertebrate proto-oncogene, c-rel. Science. 1987 Oct 30;238(4827):692–694. doi: 10.1126/science.3118464. [DOI] [PubMed] [Google Scholar]
  25. Steward R., Govind S. Dorsal-ventral polarity in the Drosophila embryo. Curr Opin Genet Dev. 1993 Aug;3(4):556–561. doi: 10.1016/0959-437x(93)90090-c. [DOI] [PubMed] [Google Scholar]
  26. Studier F. W., Moffatt B. A. Use of bacteriophage T7 RNA polymerase to direct selective high-level expression of cloned genes. J Mol Biol. 1986 May 5;189(1):113–130. doi: 10.1016/0022-2836(86)90385-2. [DOI] [PubMed] [Google Scholar]
  27. Sun S. C., Faye I. Cecropia immunoresponsive factor, an insect immunoresponsive factor with DNA-binding properties similar to nuclear-factor kappa B. Eur J Biochem. 1992 Mar 1;204(2):885–892. doi: 10.1111/j.1432-1033.1992.tb16708.x. [DOI] [PubMed] [Google Scholar]
  28. Szabad J., Erdélyi M., Hoffmann G., Szidonya J., Wright T. R. Isolation and characterization of dominant female sterile mutations of Drosophila melanogaster. II. Mutations on the second chromosome. Genetics. 1989 Aug;122(4):823–835. doi: 10.1093/genetics/122.4.823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Thisse C., Perrin-Schmitt F., Stoetzel C., Thisse B. Sequence-specific transactivation of the Drosophila twist gene by the dorsal gene product. Cell. 1991 Jun 28;65(7):1191–1201. doi: 10.1016/0092-8674(91)90014-p. [DOI] [PubMed] [Google Scholar]
  30. Williams B. R. Transcriptional regulation of interferon-stimulated genes. Eur J Biochem. 1991 Aug 15;200(1):1–11. doi: 10.1111/j.1432-1033.1991.tb21041.x. [DOI] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES