drosophila eya regulates the immune response against dna through an evolutionarily conserved threonine phosphatase motif果蝇eya调节免疫反应对dna通过进化守恒的苏氨酸磷酸酶的主题.pdfVIP

Drosophila EYA Regulates the Immune Response against DNA through an Evolutionarily Conserved Threonine Phosphatase Motif Xi Liu1,2., Teruyuki Sano4,5.¤, Yongsheng Guan1., Shigekazu Nagata4,5*, Jules A. Hoffmann2,3, Hidehiro Fukuyama1* ´ 1 INSERM Equipe Avenir, CNRS UPR9022, Institut de Biologie Moleculaire et Cellulaire, Strasbourg, France, 2 University of Strasbourg, Strasbourg, France, 3 CNRS UPR9022, ´ Institut de Biologie Moleculaire et Cellulaire, Strasbourg, France, 4 Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto, Japan, 5 Solution Oriented Research for Science and Technology, and Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kyoto, Japan Abstract Innate immune responses against DNA are essential to counter both pathogen infections and tissue damages. Mammalian EYAs were recently shown to play a role in regulating the innate immune responses against DNA. Here, we demonstrate that the unique Drosophila eya gene is also involved in the response specific to DNA. Haploinsufficiency of eya in mutants deficient for lysosomal DNase activity (DNaseII) reduces antimicrobial peptide gene expression, a hallmark for immune responses in flies. Like the mammalian orthologues, Drosophila EYA features a N-terminal threonine and C-terminal tyrosine phosphatase domain. Through the generation of a series of mutant EYA fly strains, we show that the threonine phosphatase domain, but not the tyrosine phosphatase domain, is responsible for the innate immune response against DNA. A similar role for the threonine phosphatase domain in mammalian EYA4 had been surmised on the basis of in vitro studies. Furthermore EYA associates with IKKb and full-length RELISH,