Two roles for the Drosophila IKK complex in the activation of Relish and the induction of antimicrobial peptide genes

被引:130
作者
Erturk-Hasdemir, Deniz [1 ]
Broemer, Meike [2 ]
Leulier, Francois [2 ]
Lane, William S. [3 ]
Paquette, Nicholas [1 ]
Hwang, Daye [1 ]
Kim, Chan-Hee [1 ]
Stoven, Svenja [4 ]
Meier, Pascal [2 ]
Silverman, Neal [1 ]
机构
[1] Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis, Worcester, MA 01605 USA
[2] Inst Canc Res, Breakthrough Toby Robins Breast Canc Res Ctr, London SW3 6JB, England
[3] Harvard Univ, FAS Ctr Syst Biol, Harvard Mass Spectrometry & Prote Resource Lab, Cambridge, MA 02138 USA
[4] Umea Univ, Dept Clin Microbiol, SE-90185 Umea, Sweden
基金
美国国家卫生研究院;
关键词
Drosophila immunity; innate immunity; NF-kappa B; caspase; RNA-POLYMERASE-II; NF-KAPPA-B; INSECT IMMUNITY; DIPTERICIN PROMOTER; HOST-DEFENSE; IMD-PATHWAY; TRANSCRIPTION; INFECTION; DEFINES; KINASE;
D O I
10.1073/pnas.0812022106
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The Drosophila NF-kappa B transcription factor Relish is an essential regulator of antimicrobial peptide gene induction after Gram-negative bacterial infection. Relish is a bipartite NF-kappa B precursor protein, with an N-terminal Rel homology domain and a C-terminal I kappa B-like domain, similar to mammalian p100 and p105. Unlike these mammalian homologs, Relish is endoproteolytically cleaved after infection, allowing the N-terminal NF-kappa B module to translocate to the nucleus. Signal-dependent activation of Relish, including cleavage, requires both the Drosophila I kappa B 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.
引用
收藏
页码:9779 / 9784
页数:6
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