Two roles for the Drosophila IKK complex in the activation of Relish and the induction of antimicrobial peptide genes
Authors
Erturk Hasdemir, DenizBroemer, Meike
Leulier, Francois
Lane, William S.
Paquette, Nicholas Paul
Hwang, Daye
Kim, Chan-Hee
Stoven, Svenja
Meier, Pascal
Silverman, Neal S.
UMass Chan Affiliations
Department of Medicine, Division of Infectious Diseases and ImmunologyDocument Type
Journal ArticlePublication Date
2009-06-06Keywords
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
Metadata
Show full item recordAbstract
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.Source
Proc Natl Acad Sci U S A. 2009 Jun 16;106(24):9779-84. Epub 2009 Jun 2. Link to article on publisher's siteDOI
10.1073/pnas.0812022106Permanent Link to this Item
http://hdl.handle.net/20.500.14038/34958PubMed ID
19497884Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1073/pnas.0812022106