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

Ertürk-Hasdemir, Deniz; Broemer, Meike; Leulier, François; Lane, William S.; Paquette, Nicholas; Hwang, Daye; Kim, Chan-Hee; Stöven, Svenja; Meier, Pascal; Silverman, Neal S.

doi:10.1073/pnas.0812022106

Cited by 148 publications

(154 citation statements)

References 36 publications

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“…We observed that the tagged RelN in our coimmunoprecipitation assays had a strong tendency to dimerize with Relish but did not exhibit the same tendency toward Dorsal or DIF (lanes [13][14][15][16]. Therefore, in these assays, RelN exhibited a different binding pattern than Relish for the interaction with DIF.…”

Section: Dorsal Dif and Relish Dimer Combinations Are Detectable In Amentioning

confidence: 72%

“…These regulators converge signals onto the transcription factor Relish, the third Drosophila NF-κB-related protein that is homologous to NF-κB1 (p105) in mammals. Relish is cleaved during signal stimulation and the N-terminal fragment translocates to the nucleus (16). Once in the nucleus, Relish regulates a different subset of antimicrobial peptide genes (11,17).…”

mentioning

confidence: 99%

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Heterodimers of NF-κB transcription factors DIF and Relish regulate antimicrobial peptide genes in Drosophila

Tanji

Yun

2010

Proc. Natl. Acad. Sci. U.S.A.

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The innate immune response in Drosophila involves the inducible expression of antimicrobial peptide genes mediated by the Toll and IMD signaling pathways. Dorsal and DIF act downstream of Toll, whereas Relish acts downstream of IMD to regulate target gene expression. Dorsal, DIF, and Relish are NF-κB-related transcription factors and function as obligate dimers, but it is not clear how the various dimer combinations contribute to the innate immune response. We systematically examined the dimerization tendency of these proteins through the use of transgenic assays. The results show that all combinations of homo-and heterodimers are formed, but with varying degrees of efficiency. The formation of the DIFRelish heterodimer is particularly interesting because it may mediate signaling for the seemingly independent Toll and IMD pathways. By incorporating a flexible peptide linker, we specifically tested the functions of the DIF^Relish (a^sign represents the peptide linker) linked heterodimer. Our results demonstrate that the linked heterodimer can activate target genes of both the Toll and IMD pathways. The DIF and Relish complex is detectable in whole animal extracts, suggesting that this heterodimer may function in vivo to increase the spectrum and level of antimicrobial peptide production in response to different infections.IMD | innate immunity | Toll

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Section: Dorsal Dif and Relish Dimer Combinations Are Detectable In Amentioning

confidence: 72%

mentioning

confidence: 99%

Heterodimers of NF-κB transcription factors DIF and Relish regulate antimicrobial peptide genes in Drosophila

Tanji

Yun

2010

Proc. Natl. Acad. Sci. U.S.A.

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“…This brings Relish into close proximity of ubiquitylated and active DREDD, allowing DREDDmediated proteolysis of Relish. The proximity to the signaling complex also allows phosphomediated activation of Relish (Erturk-Hasdemir et al 2009). Subsequently, cleaved and phosphoryated Relish translocates to the nucleus where it drives expression of antimicrobial peptide genes.…”

Section: Iap-mediated Regulation Of Innate Immunity and Cell Survivalmentioning

confidence: 99%

Inhibitor of Apoptosis (IAP) Proteins-Modulators of Cell Death and Inflammation

Silke

Meier

2013

Cold Spring Harbor Perspectives in Biology

283

214

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“…Once activated, dTAK1 initiates two downstream arms of the IMD pathway. In the Relish/NF-κB arm, dTAK1 phosphorylates and activates the IKK complex leading to the subsequent phosphorylation and activation of the NF-κB protein Relish, which drives the expression of a battery of antimicrobial peptide genes (19,20). In the second arm of the IMD pathway, dTAK1 also activates the JNK kinase Hemipterous, which, in turn, phosphorylates the JNK homolog Basket, leading to the activation of AP1 transcription factors and induction of various immune genes (19,21).…”

Section: Drosophila Immunity | Innate Immunitymentioning

confidence: 99%

Serine/threonine acetylation of TGFβ-activated kinase (TAK1) by Yersinia pestis YopJ inhibits innate immune signaling

Paquette

Conlon²,

Sweet³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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161

130

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The Gram-negative bacteria Yersinia pestis , causative agent of plague, is extremely virulent. One mechanism contributing to Y. pestis virulence is the presence of a type-three secretion system, which injects effector proteins, Yops, directly into immune cells of the infected host. One of these Yop proteins, YopJ, is proapoptotic and inhibits mammalian NF-κB and MAP-kinase signal transduction pathways. Although the molecular mechanism remained elusive for some time, recent work has shown that YopJ acts as a serine/threonine acetyl-transferase targeting MAP2 kinases. Using Drosophila as a model system, we find that YopJ inhibits one innate immune NF-κB signaling pathway (IMD) but not the other (Toll). In fact, we show YopJ mediated serine/threonine acetylation and inhibition of dTAK1, the critical MAP3 kinase in the IMD pathway. Acetylation of critical serine/threonine residues in the activation loop of Drosophila TAK1 blocks phosphorylation of the protein and subsequent kinase activation. In addition, studies in mammalian cells show similar modification and inhibition of hTAK1. These data present evidence that TAK1 is a target for YopJ-mediated inhibition.

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

Cited by 148 publications

References 36 publications

Heterodimers of NF-κB transcription factors DIF and Relish regulate antimicrobial peptide genes in Drosophila

Heterodimers of NF-κB transcription factors DIF and Relish regulate antimicrobial peptide genes in Drosophila

Inhibitor of Apoptosis (IAP) Proteins-Modulators of Cell Death and Inflammation

Serine/threonine acetylation of TGFβ-activated kinase (TAK1) by Yersinia pestis YopJ inhibits innate immune signaling

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