REGULATED NUCLEAR IMPORT OF REL PROTEINS IN THE DROSOPHILA IMMUNE-RESPONSE

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-kappa B family(1-4). In r esponse to infection, two Rel proteins, Dif and Dorsal, translocate fr om the cytoplasm to the nuclei of larval fat-body cells(1,2,5). The To ll signalling pathway, which controls dorsal-ventral patterning during Drosophila embryogenesis(6), regulates the nuclear import of Dorsal i n the immune response(2,7), 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 signal ling pathways that target Cactus for degradation must discriminate bet ween Cactus-Dorsal and Cactus-Dif complexes. We identified new genes t hat are required for normal induction of transcription of an antibacte rial peptide during the immune response. Mutations in three of these g enes prevent nuclear import of Dif in response to infection, and defin e new components of signalling pathways involving Rel. Mutations in th ree other genes cause constitutive nuclear localization of Dif; these mutations may block Rel protein activity by a novel mechanism.