The role of ubiquitination in Drosophila innate immunity
Department of Medicine, Division of Infectious Diseases and Immunology
Animals; Cell Culture Techniques; Drosophila; Evolution, Molecular; Gram-Negative Bacterial Infections; I-kappa B Kinase; Immunity, Natural; MAP Kinase Kinase 4; Signal Transduction; Ubiquitin-Conjugating Enzymes
Infection of Drosophila by Gram-negative bacteria triggers a signal transduction pathway (the IMD pathway) culminating in the expression of genes encoding antimicrobial peptides. A key component in this pathway is a Drosophila IkappaB kinase (DmIKK) complex, which stimulates the cleavage and activation of the NF-kappaB transcription factor Relish. Activation of the DmIKK complex requires the MAP3K dTAK1, but the mechanism of dTAK1 activation is not understood. In human cells, the activation of TAK1 and IKK requires the human ubiquitin-conjugating enzymes Ubc13 and UEV1a. Here we demonstrate that the Drosophila homologs of Ubc13 and UEV1a are similarly required for the activation of dTAK1 and the DmIKK complex. Surprisingly, we find that the Drosophila caspase DREDD and its partner dFADD are required for the activation of DmIKK and JNK, in addition to their role in Relish cleavage. These studies reveal an evolutionarily conserved role of ubiquitination in IKK activation, and provide new insights into the hierarchy of signaling components in the Drosophila antibacterial immunity pathway.
Rights and Permissions
Citation: J Biol Chem. 2005 Oct 7;280(40):34048-55. Epub 2005 Aug 4. Link to article on publisher's site
Zhou, Rui; Silverman, Neal S.; Hong, Mei; Liao, Dorothy S.; Chung, Yvonne; Chen, Zhijian J.; and Maniatis, Tom, "The role of ubiquitination in Drosophila innate immunity" (2005). Infectious Diseases and Immunology Publications and Presentations. 10.