Abstract
The Drosophila immune response uses many of the same components as the mammalian innate immune response, including signalling pathways that activate transcription factors of the Rel/NK-κB family1,2,3,4. In response to infection, two Rel proteins, Dif and Dorsal, translocate from the cytoplasm to the nuclei of larval fat-body cells1,2,5. The Toll signalling pathway, which controls dorsal–ventral patterning during Drosophila embryogenesis6, regulates the nuclear import of Dorsal in the immune response2,7, but here we show that the Toll pathway is not required for nuclear import of Dif. Cytoplasmic retention of both Dorsal and Dif depends on Cactus protein; nuclear import of Dorsal and Dif is accompanied by degradation of Cactus. Therefore the two signalling pathways that target Cactus for degradation must discriminate between Cactus–Dorsal and Cactus–Dif complexes. We identified new genes that are required for normal induction of transcription of an antibacterial peptide during the immune response. Mutations in three of these genes prevent nuclear import of Dif in response to infection, and define new components of signalling pathways involving Rel. Mutations in three other genes cause constitutive nuclear localization of Dif; these mutations may block Rel protein activity by a novel mechanism.
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Acknowledgements
We thank R. Steward for antibodies to Dorsal and Cactus; Y. Engström for antibody against Dif; B. Lemaitre for the diptericin-lacZ transgenic flies; M. Dushay for the diptericin cDNA; Y. Lu and S. Li for help with mapping; and M. Baylies, M. Belvin and T. Bestor for comments on the manuscript. This work was supported by NIH and NSF grants to K.V.A. and the Memorial Sloan-Kettering Cancer Center Support Grant. L.P.W. is a Leukemia Society of America Special Fellow.
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Wu, L., Anderson, K. Regulated nuclear import of Rel proteins in the Drosophila immune response. Nature 392, 93–97 (1998). https://doi.org/10.1038/32195
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DOI: https://doi.org/10.1038/32195
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