Authors
Zhou, RuiSilverman, Neal S.
Hong, Mei
Liao, Dorothy S.
Chung, Yvonne
Chen, Zhijian J.
Maniatis, Tom
UMass Chan Affiliations
Department of Medicine, Division of Infectious Diseases and ImmunologyDocument Type
Journal ArticlePublication Date
2005-08-06Keywords
AnimalsCell Culture Techniques
Drosophila
Evolution, Molecular
Gram-Negative Bacterial Infections
I-kappa B Kinase
Immunity, Natural
MAP Kinase Kinase 4
Signal Transduction
Ubiquitin-Conjugating Enzymes
Immunology and Infectious Disease
Metadata
Show full item recordAbstract
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.Source
J Biol Chem. 2005 Oct 7;280(40):34048-55. Epub 2005 Aug 4. Link to article on publisher's siteDOI
10.1074/jbc.M506655200Permanent Link to this Item
http://hdl.handle.net/20.500.14038/34870PubMed ID
16081424Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1074/jbc.M506655200