κB-like Motifs Regulate the Induction of Immune Genes in Drosophila

Engström, Ylva; Kadalayil, Latha; Sun, Shao Cong; Samakovlis, Christos; Hultmark, Dan; Faye, Ingrid

doi:10.1006/jmbi.1993.1392

Cited by 209 publications

(149 citation statements)

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“…Reporter plasmids for chloramphenicol transferase (CAT) and Cecropin A1-lacZ (24) were cotransfected along with the Relish constructs. Before lipopolysaccharide (LPS) addition, half of each culture was harvested to serve as the uninduced sample.…”

Section: Methodsmentioning

confidence: 99%

Caspase-mediated processing of the Drosophila NF-κB factor Relish

Stöven

Silverman

Junell

et al. 2003

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

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Section: Methodsmentioning

confidence: 99%

Caspase-mediated processing of the Drosophila NF-κB factor Relish

Stöven

Silverman

Junell

et al. 2003

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

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302

291

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“…T ranscriptional regulation of Drosophila antimicrobial genes depends on Rel and GATA transcription factors (1)(2)(3)(4)(5)(6). Many immunity genes contain tightly linked Rel-and GATAbinding sites in promoter-proximal regions.…”

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confidence: 99%

DEAF-1 regulates immunity gene expression in Drosophila

Reed

Huang

Wohlschlegel

et al. 2008

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

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Immunity genes are activated in the Drosophila fat body by Rel and GATA transcription factors. Here, we present evidence that an additional regulatory factor, deformed epidermal autoregulatory factor-1 (DEAF-1), also contributes to the immune response and is specifically important for the induction of two genes encoding antimicrobial peptides, Metchnikowin (Mtk) and Drosomycin (Drs). The systematic mutagenesis of a minimal Mtk 5 enhancer identified a sequence motif essential for both a response to LPS preparations in S2 cells and activation in the larval fat body in response to bacterial infection. Using affinity chromatography coupled to multidimensional protein identification technology (MudPIT), we identified DEAF-1 as a candidate regulator. DEAF-1 activates the expression of Mtk and Drs promoter-luciferase fusion genes in S2 cells. SELEX assays and footprinting data indicate that DEAF-1 binds to and activates Mtk and Drs regulatory DNAs via a TTCGGBT motif. The insertion of this motif into the Diptericin (Dpt) regulatory region confers DEAF-1 responsiveness to this normally DEAF-1-independent enhancer. The coexpression of DEAF-1 with Dorsal, Dif, and Relish results in the synergistic activation of transcription. We propose that DEAF-1 is a regulator of Drosophila immunity.T ranscriptional regulation of Drosophila antimicrobial genes depends on Rel and GATA transcription factors (1-6). Many immunity genes contain tightly linked Rel-and GATAbinding sites in promoter-proximal regions. GATA sites are important for establishing responses in distinct tissues such as the fat body and midgut. Serpent (dGATAb) is thought to regulate antimicrobial gene expression in the fat body (7, 8), whereas dGATAe activates such genes in the midgut in response to ingested microbes (9). In contrast, Dorsal, Dif, and Relish, the NF-B homologues in flies, shuttle between the cytoplasmic and nuclear compartments, acting as ''on/off switches'' for induction (10)(11)(12). Additional factors, such as HOX and POU domain proteins, bind to distal enhancer elements and maintain constitutive domains of gene activity (13). A regulatory element (R1) also has been described within the CecA1 enhancer (14), although the factor that interacts with this motif is unknown.Deformed epidermal autoregulatory factor-1 (DEAF-1) is a transcription factor that was originally shown to bind the autoregulatory enhancer of the Deformed (Dfd) Hox gene, which is activated in embryonic head segments of Drosophila (15). DEAF-1 recognizes several TTCG motifs within the portion of the Dfd autoregulatory region termed ''module E.'' In addition, DEAF-1 binds several similar motifs within a Dfd response element (DRE) from the 1.28 gene that enhances maxillary gene expression during embryogenesis (16). The DEAF-1 binding elements identified in these studies are reportedly not required for enhancer activity however (16,17).The 576-aa DEAF-1 protein possesses two conserved domains, SAND and MYND. The 113-aa SAND domain (named for SP100, AIRE-1, NucP41/75, and DEAF-1) (18) i...

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“…20). Experiments with transgenic flies have shown that these motifs are mandatory for immune inducibility of the insect antibacterial peptide genes (21,22). Several Rel proteins were reported to be present in the fat body: DL (23), initially identified as the dorsoventral morphogen, DIF (for dorsal-related immunity factor; Ref.…”

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confidence: 99%

In Vivo Regulation of the IκB Homologue cactus during the Immune Response of Drosophila

Nicolas

Reichhart

Hoffmann

et al. 1998

Journal of Biological Chemistry

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The dorsoventral regulatory gene pathway (spä tzle/ Toll/cactus) controls the expression of several antimicrobial genes during the immune response of Drosophila. This regulatory cascade shows striking similarities with the cytokine-induced activation cascade of NF-B during the inflammatory response in mammals. Here, we have studied the regulation of the I B homologue Cactus in the fat body during the immune response. We observe that the cactus gene is up-regulated in response to immune challenge. Interestingly, the expression of the cactus gene is controlled by the spä tzle/Toll/cactus gene pathway, indicating that the cactus gene is autoregulated. We also show that two Cactus isoforms are expressed in the cytoplasm of fat body cells and that they are rapidly degraded and resynthesized after immune challenge. This degradation is also dependent on the Toll signaling pathway. Altogether, our results underline the striking similarities between the regulation of I B and cactus during the immune response.

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κB-like Motifs Regulate the Induction of Immune Genes in Drosophila

Cited by 209 publications

References 0 publications

Caspase-mediated processing of the Drosophila NF-κB factor Relish

Caspase-mediated processing of the Drosophila NF-κB factor Relish

DEAF-1 regulates immunity gene expression in Drosophila

In Vivo Regulation of the IκB Homologue cactus during the Immune Response of Drosophila

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