Two roles for the Drosophila IKK complex in the activation of Relish and the induction of antimicrobial peptide genes.
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.
Ertürk-Hasdemir
Deniz
D
Division of Infectious Diseases, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Broemer
Meike
M
Leulier
François
F
Lane
William S
WS
Paquette
Nicholas
N
Hwang
Daye
D
Kim
Chan-Hee
CH
Stöven
Svenja
S
Meier
Pascal
P
Silverman
Neal
N
D000818:Animals; D000890:Anti-Infective Agents; D004330:Drosophila; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D004843:Epistasis, Genetic; D005786:Gene Expression Regulation; D051550:I-kappa B Kinase / Q000737:chemistry / Q000502:physiology*; D010455:Peptides / Q000235:genetics*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D012694:Serine / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
D000890:Anti-Infective Agents; D029721:Drosophila Proteins; D010455:Peptides; C101626:Rel protein, Drosophila; D014157:Transcription Factors; D012694:Serine; D051550:I-kappa B Kinase; C496563:IKKbeta protein, Drosophila