Two roles for the Drosophila IKK complex in the activation of Relish and the induction of antimicrobial peptide genes
Department of Medicine, Division of Infectious Diseases and Immunology
Animals; *Anti-Infective Agents; Drosophila; Drosophila Proteins; Epistasis, Genetic; *Gene Expression Regulation; I-kappa B Kinase; Peptides; Phosphorylation; Promoter Regions, Genetic; Serine; Transcription Factors
Immunology and Infectious Disease
The Drosophila NF-kappaB transcription factor Relish is an essential regulator of antimicrobial peptide gene induction after gram-negative bacterial infection. Relish is a bipartite NF-kappaB precursor protein, with an N-terminal Rel homology domain and a C-terminal IkappaB-like domain, similar to mammalian p100 and p105. Unlike these mammalian homologs, Relish is endoproteolytically cleaved after infection, allowing the N-terminal NF-kappaB module to translocate to the nucleus. Signal-dependent activation of Relish, including cleavage, requires both the Drosophila IkappaB kinase (IKK) and death-related ced-3/Nedd2-like protein (DREDD), the Drosophila caspase-8 like protease. In this report, we show that the IKK complex controls Relish by direct phosphorylation on serines 528 and 529. Surprisingly, these phosphorylation sites are not required for Relish cleavage, nuclear translocation, or DNA binding. Instead they are critical for recruitment of RNA polymerase II and antimicrobial peptide gene induction, whereas IKK functions noncatalytically to support Dredd-mediated cleavage of Relish.
DOI of Published Version
Proc Natl Acad Sci U S A. 2009 Jun 16;106(24):9779-84. Epub 2009 Jun 2. Link to article on publisher's site
Proceedings of the National Academy of Sciences of the United States of America
Erturk Hasdemir, Deniz; Broemer, Meike; Leulier, Francois; Lane, William S.; Paquette, Nicholas Paul; Hwang, Daye; Kim, Chan-Hee; Stoven, Svenja; Meier, Pascal; and Silverman, Neal S., "Two roles for the Drosophila IKK complex in the activation of Relish and the induction of antimicrobial peptide genes" (2009). Infectious Diseases and Immunology Publications and Presentations. 18.