Genomes and Genes
Gene Symbol: key
Alias: CG16910, DmIKK-gamma, DmIKKgamma, Dmel\CG16910, Dmikkgamma, IKK, IKK-gamma, IKKG, IKK[[gamma]], IKKg, IKKgamma, KEY, Kenny, Key, dIKK, dIKK-gamma, dmIKKgamma, kenny, CG16910-PA, CG16910-PB, kenney, key-PA, key-PB
Species: fruit fly
- Gesellchen V, Kuttenkeuler D, Steckel M, Pelte N, Boutros M. An RNA interference screen identifies Inhibitor of Apoptosis Protein 2 as a regulator of innate immune signalling in Drosophila. EMBO Rep. 2005;6:979-84 pubmed..Our results indicate that IAP gene family members may have acquired other functions, such as the regulation of the tumour necrosis factor-like IMD pathway during innate immune responses. ..
- Rutschmann S, Jung A, Zhou R, Silverman N, Hoffmann J, Ferrandon D. Role of Drosophila IKK gamma in a toll-independent antibacterial immune response. Nat Immunol. 2000;1:342-7 pubmed..loss-of-function mutants in the Drosophila homolog of the mammalian I-kappa B kinase (IKK) complex component IKK gamma (also called NEMO)...
- Vidal S, Khush R, Leulier F, Tzou P, Nakamura M, Lemaitre B. Mutations in the Drosophila dTAK1 gene reveal a conserved function for MAPKKKs in the control of rel/NF-kappaB-dependent innate immune responses. Genes Dev. 2001;15:1900-12 pubmed..Our genetic studies also indicate that dTAK1 functions downstream of the Imd protein and upstream of the IKK complex in the Imd pathway that controls the Rel/NF-kappaB like transactivator Relish...
- Georgel P, Naitza S, Kappler C, Ferrandon D, Zachary D, Swimmer C, et al. Drosophila immune deficiency (IMD) is a death domain protein that activates antibacterial defense and can promote apoptosis. Dev Cell. 2001;1:503-14 pubmed..We also show that imd is involved in the apoptotic response to UV irradiation. These data raise the possibility that antibacterial response and apoptosis share common control elements in Drosophila. ..
- Hoffmann J. The immune response of Drosophila. Nature. 2003;426:33-8 pubmed..Recent progress in research on Drosophila immune defence provides evidence for similarities and differences between Drosophila immune responses and mammalian innate immunity. ..
- Kaneko T, Yano T, Aggarwal K, Lim J, Ueda K, Oshima Y, et al. PGRP-LC and PGRP-LE have essential yet distinct functions in the drosophila immune response to monomeric DAP-type peptidoglycan. Nat Immunol. 2006;7:715-23 pubmed..These data demonstrate that like mammals, drosophila use both extracellular and intracellular receptors, which have conserved signaling mechanisms, for innate immune recognition...
- Nehme N, Liegeois S, Kele B, Giammarinaro P, Pradel E, Hoffmann J, et al. A model of bacterial intestinal infections in Drosophila melanogaster. PLoS Pathog. 2007;3:e173 pubmed..Thanks to the genetic tools available in both host and pathogen, the molecular dissection of the interactions between S. marcescens and Drosophila will provide a useful paradigm for deciphering intestinal pathogenesis...
- Erturk Hasdemir D, Broemer M, Leulier F, Lane W, Paquette N, Hwang D, et al. Two roles for the Drosophila IKK complex in the activation of Relish and the induction of antimicrobial peptide genes. Proc Natl Acad Sci U S A. 2009;106:9779-84 pubmed publisher..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...
- Wang Z, Berkey C, Watnick P. The Drosophila protein mustard tailors the innate immune response activated by the immune deficiency pathway. J Immunol. 2012;188:3993-4000 pubmed publisher..Mtd homologs have been implicated in resistance to oxidative stress. However, to our knowledge this is the first evidence that Mtd or its homologs alter the output of an innate immunity signaling cascade from within the nucleus...
- Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell. 2006;124:783-801 pubmed..New insights into innate immunity are changing the way we think about pathogenesis and the treatment of infectious diseases, allergy, and autoimmunity. ..
- Stoven S, Silverman N, Junell A, Hedengren Olcott M, Erturk D, Engstrom Y, et al. Caspase-mediated processing of the Drosophila NF-kappaB factor Relish. Proc Natl Acad Sci U S A. 2003;100:5991-6 pubmed..Finally, an N-terminal serine-rich region in Relish and the PEST domain were found to negatively regulate Relish activation. ..
- Sabatier L, Jouanguy E, Dostert C, Zachary D, Dimarcq J, Bulet P, et al. Pherokine-2 and -3. Eur J Biochem. 2003;270:3398-407 pubmed..Both Phk-2 and Phk-3 are strongly expressed during metamorphosis, suggesting that they may participate in tissue-remodeling. ..
- Bischoff V, Vignal C, Boneca I, Michel T, Hoffmann J, Royet J. Function of the drosophila pattern-recognition receptor PGRP-SD in the detection of Gram-positive bacteria. Nat Immunol. 2004;5:1175-80 pubmed..These data indicate that PGRP-SD can function as a receptor for Gram-positive bacteria and shows partial redundancy with the PGRP-SA-GNBP1 complex. ..
- Michel T, Reichhart J, Hoffmann J, Royet J. Drosophila Toll is activated by Gram-positive bacteria through a circulating peptidoglycan recognition protein. Nature. 2001;414:756-9 pubmed..Interestingly, seml does not affect Toll activation by fungal infection, indicating the existence of a distinct recognition system for fungi to activate the Toll pathway...
- Leone P, Bischoff V, Kellenberger C, Hetru C, Royet J, Roussel A. Crystal structure of Drosophila PGRP-SD suggests binding to DAP-type but not lysine-type peptidoglycan. Mol Immunol. 2008;45:2521-30 pubmed publisher..Our hypothesis is that the role of PGRP-SD is the recognition of DAP-type PGNs responsible for the activation of the Toll pathway by Gram-negative bacteria. ..
- Gobert V, Gottar M, Matskevich A, Rutschmann S, Royet J, Belvin M, et al. Dual activation of the Drosophila toll pathway by two pattern recognition receptors. Science. 2003;302:2126-30 pubmed..The potential for a combination of distinct proteins to mediate detection of infectious nonself in the fly will refine the concept of pattern recognition in insects. ..
- Gottar M, Gobert V, Matskevich A, Reichhart J, Wang C, Butt T, et al. Dual detection of fungal infections in Drosophila via recognition of glucans and sensing of virulence factors. Cell. 2006;127:1425-37 pubmed..Thus, the detection of fungal infections in Drosophila relies both on the recognition of invariant microbial patterns and on monitoring the effects of virulence factors on the host. ..
- Gottar M, Gobert V, Michel T, Belvin M, Duyk G, Hoffmann J, et al. The Drosophila immune response against Gram-negative bacteria is mediated by a peptidoglycan recognition protein. Nature. 2002;416:640-4 pubmed..The data on PGRP-SA with respect to the response to Gram-positive infections, together with the present report, indicate that the PGRP family has a principal role in sensing microbial infections in Drosophila. ..
- Silverman N, Zhou R, Stoven S, Pandey N, Hultmark D, Maniatis T. A Drosophila IkappaB kinase complex required for Relish cleavage and antibacterial immunity. Genes Dev. 2000;14:2461-71 pubmedHere we report the identification of a Drosophila IkappaB kinase complex containing DmIKKbeta and DmIKKgamma, homologs of the human IKKbeta and IKKgamma proteins...
- Shirinian M, Kambris Z, Hamadeh L, Grabbe C, Journo C, Mahieux R, et al. A Transgenic Drosophila melanogaster Model To Study Human T-Lymphotropic Virus Oncoprotein Tax-1-Driven Transformation In Vivo. J Virol. 2015;89:8092-5 pubmed publisher..We demonstrate that Tax-1 but not Tax-2 induces ommatidial perturbation and increased plasmatocyte proliferation and that the eye phenotype is dependent on Kenny (IKKÎ³/NEMO), thus validating this new in vivo model.
- Williams J, Sathyanarayanan S, Hendricks J, Sehgal A. Interaction between sleep and the immune response in Drosophila: a role for the NFkappaB relish. Sleep. 2007;30:389-400 pubmed..These results demonstrate a conserved interaction between sleep and the immune system. Genetic manipulation of an immune component alters sleep, and likewise, acute sleep deprivation alters the immune response. ..
- Bou Aoun R, Hetru C, Troxler L, Doucet D, Ferrandon D, Matt N. Analysis of thioester-containing proteins during the innate immune response of Drosophila melanogaster. J Innate Immun. 2011;3:52-64 pubmed publisher..TEPs may thus provide a subtle selective advantage during evolution. Alternatively, they may be required in host defense against specific as yet unidentified natural pathogens of Drosophila. ..
- Avadhanula V, Weasner B, Hardy G, Kumar J, Hardy R. A novel system for the launch of alphavirus RNA synthesis reveals a role for the Imd pathway in arthropod antiviral response. PLoS Pathog. 2009;5:e1000582 pubmed publisher..These findings show that the Imd pathway mediates an antiviral response to Sindbis virus replication. To our knowledge, this is the first demonstration of an antiviral role for the Imd pathway in insects. ..
- Costa A, Jan E, Sarnow P, Schneider D. The Imd pathway is involved in antiviral immune responses in Drosophila. PLoS ONE. 2009;4:e7436 pubmed publisher..Our data show that antiviral innate immune responses in flies infected with CrPV depend upon hemocytes and signaling through the Imd pathway. ..
- Mulinari S, Hacker U, Castillejo Lopez C. Expression and regulation of Spätzle-processing enzyme in Drosophila. FEBS Lett. 2006;580:5406-10 pubmed
- Glittenberg M, Kounatidis I, Christensen D, Kostov M, Kimber S, Roberts I, et al. Pathogen and host factors are needed to provoke a systemic host response to gastrointestinal infection of Drosophila larvae by Candida albicans. Dis Model Mech. 2011;4:515-25 pubmed publisher..The secretion of SAP4 and SAP6 (secreted aspartyl proteases) from Candida was also essential for activating systemic Toll-dependent immunity. ..
- Tsichritzis T, Gaentzsch P, Kosmidis S, Brown A, SKOULAKIS E, Ligoxygakis P, et al. A Drosophila ortholog of the human cylindromatosis tumor suppressor gene regulates triglyceride content and antibacterial defense. Development. 2007;134:2605-14 pubmed..All mutant phenotypes described were reversible upon conditional expression of CYLD transgenes. Our results implicate CYLD in a broad range of functions associated with fat homeostasis and host defence in Drosophila. ..
- Bergeret E, Perrin J, Williams M, Grunwald D, Engel E, Thevenon D, et al. TM9SF4 is required for Drosophila cellular immunity via cell adhesion and phagocytosis. J Cell Sci. 2008;121:3325-34 pubmed publisher..Our study highlights the contribution of phagocytes to host defence in an organism possessing a complex innate immune response and suggests an evolutionarily conserved function of TM9SF4 in eukaryotic phagocytes. ..
- Bond D, Primrose D, Foley E. Quantitative evaluation of signaling events in Drosophila S2 cells. Biol Proced Online. 2008;10:20-8 pubmed publisher..In this report, we describe a simple method for the quantification of JNK activation by Western blot analysis or directly in tissue culture plates. ..
- Vandenabeele P, Bertrand M. The role of the IAP E3 ubiquitin ligases in regulating pattern-recognition receptor signalling. Nat Rev Immunol. 2012;12:833-44 pubmed publisher..Understanding the role of IAPs in innate immunity may open new therapeutic perspectives for the treatment of PRR-dependent inflammatory diseases. ..
- Nehme N, Quintin J, Cho J, Lee J, Lafarge M, Kocks C, et al. Relative roles of the cellular and humoral responses in the Drosophila host defense against three gram-positive bacterial infections. PLoS ONE. 2011;6:e14743 pubmed publisher..However, it is less clear to what extent macrophage-like hemocytes contribute to host defense...
- Khush R, Cornwell W, Uram J, Lemaitre B. A ubiquitin-proteasome pathway represses the Drosophila immune deficiency signaling cascade. Curr Biol. 2002;12:1728-37 pubmed..A possible target of this proteolytic activity is the Relish transcription factor, suggesting a mechanism for NF-kappaB downregulation in Drosophila. ..
- Maillet F, Bischoff V, Vignal C, Hoffmann J, Royet J. The Drosophila peptidoglycan recognition protein PGRP-LF blocks PGRP-LC and IMD/JNK pathway activation. Cell Host Microbe. 2008;3:293-303 pubmed publisher..Thus, PGRP-LF prevents constitutive activation of both the JNK and the IMD pathways. We propose a model in which PGRP-LF keeps the Drosophila IMD pathway silent by sequestering circulating peptidoglycan. ..
- Lesch C, Goto A, Lindgren M, Bidla G, Dushay M, Theopold U. A role for Hemolectin in coagulation and immunity in Drosophila melanogaster. Dev Comp Immunol. 2007;31:1255-63 pubmed..This demonstrates an immunological role of this clotting protein and reinforces the importance of the clot in insect immunity. ..
- Limmer S, Haller S, Drenkard E, Lee J, Yu S, Kocks C, et al. Pseudomonas aeruginosa RhlR is required to neutralize the cellular immune response in a Drosophila melanogaster oral infection model. Proc Natl Acad Sci U S A. 2011;108:17378-83 pubmed publisher..In contrast, the quorum-sensing transcription factor RhlR, but surprisingly not LasR, played a key role in counteracting the cellular immune response against PA14, possibly at an early stage when only a few ..
- McGettigan J, McLennan R, Broderick K, Kean L, Allan A, Cabrero P, et al. Insect renal tubules constitute a cell-autonomous immune system that protects the organism against bacterial infection. Insect Biochem Mol Biol. 2005;35:741-54 pubmed..coli challenge. Thus, we describe a novel role of Malpighian tubules in immune sensing and insect survival. ..
- Goto A, Yano T, Terashima J, Iwashita S, Oshima Y, Kurata S. Cooperative regulation of the induction of the novel antibacterial Listericin by peptidoglycan recognition protein LE and the JAK-STAT pathway. J Biol Chem. 2010;285:15731-8 pubmed publisher..Based on these findings, we propose that the Listericin gene encodes a novel antibacterial peptide-like protein whose induction is cooperatively regulated by PGRP-LE and the JAK-STAT pathway. ..
- Nelson B, Freisinger T, Ishii K, Okado K, Shinzawa N, Fukumoto S, et al. Activation of Imd pathway in hemocyte confers infection resistance through humoral response in Drosophila. Biochem Biophys Res Commun. 2013;430:1120-5 pubmed publisher..aureus, counter to notions of traditional roles of the Imd pathway thought largely to responsible for resistance to Gram-negative bacteria. ..
- Khush R, Leulier F, Lemaitre B. Immunology. Pathogen surveillance--the flies have it. Science. 2002;296:273-5 pubmed
- Quintin J, Asmar J, Matskevich A, Lafarge M, Ferrandon D. The Drosophila Toll pathway controls but does not clear Candida glabrata infections. J Immunol. 2013;190:2818-27 pubmed publisher..glabrata in this model. Unexpectedly, yapsins do not appear to be required to counteract the cellular immune response but are needed for the colonization of the wild-type host. ..
- Aymeric J, Givaudan A, Duvic B. Imd pathway is involved in the interaction of Drosophila melanogaster with the entomopathogenic bacteria, Xenorhabdus nematophila and Photorhabdus luminescens. Mol Immunol. 2010;47:2342-8 pubmed publisher..coli-induced protection. However, phoP recovered a level of pathogenicity comparable to P. luminescens wild-type TT01 when injected to Drosophila flies affected on the imd pathway. ..
- Sun H, Bristow B, Qu G, Wasserman S. A heterotrimeric death domain complex in Toll signaling. Proc Natl Acad Sci U S A. 2002;99:12871-6 pubmed..Furthermore, functional assays confirm that the formation of this heterotrimer is critical for signal transduction by the Toll pathway. ..
- Wang Z, Hang S, Purdy A, Watnick P. Mutations in the IMD pathway and mustard counter Vibrio cholerae suppression of intestinal stem cell division in Drosophila. MBio. 2013;4:e00337-13 pubmed publisher..cholerae and that accelerated epithelial regeneration protects the host against V. cholerae. Extension of these findings to mammals awaits the development of an adequate experimental model. ..
- Kim M, Lee J, Lee S, Kim E, Chung J. Caspar, a suppressor of antibacterial immunity in Drosophila. Proc Natl Acad Sci U S A. 2006;103:16358-63 pubmed..Collectively, our elucidation of an inhibitory mechanism of the Imd pathway by Caspar will provide a valuable insight into understanding complex regulatory mechanisms of the innate immune systems in both Drosophila and mammals. ..
- Glittenberg M, Ligoxygakis P. CYLD: a multifunctional deubiquitinase. Fly (Austin). 2007;1:330-2 pubmed..Recent studies have revealed a requirement for CYLD in many different processes and have provided some insight into the underlying mechanisms. ..
- Igboin C, Tordoff K, Moeschberger M, Griffen A, Leys E. Porphyromonas gingivalis-host interactions in a Drosophila melanogaster model. Infect Immun. 2011;79:449-58 pubmed publisher..This study demonstrates that the Drosophila killing model is a useful high-throughput model for characterizing the host response to P. gingivalis infection and uncovering novel interactions between the bacterium and the host. ..
- Govind S, Nehm R. Innate immunity in fruit flies: a textbook example of genomic recycling. PLoS Biol. 2004;2:E276 pubmed
- Paquette N, Broemer M, Aggarwal K, Chen L, Husson M, Erturk Hasdemir D, et al. Caspase-mediated cleavage, IAP binding, and ubiquitination: linking three mechanisms crucial for Drosophila NF-kappaB signaling. Mol Cell. 2010;37:172-82 pubmed publisher..Through its association with DIAP2, IMD is rapidly conjugated with K63-linked polyubiquitin chains. These results mechanistically connect caspase-mediated cleavage and K63 ubiquitination in immune-induced NF-kappaB signaling. ..
- Douglas A, Bouvaine S, Russell R. How the insect immune system interacts with an obligate symbiotic bacterium. Proc Biol Sci. 2011;278:333-8 pubmed publisher..They support the proposed contribution of the Buchnera symbiosis to the evolution of the apparently reduced immune function in the aphid host. ..
- Filipe S, Tomasz A, Ligoxygakis P. Requirements of peptidoglycan structure that allow detection by the Drosophila Toll pathway. EMBO Rep. 2005;6:327-33 pubmed..We suggest a model whereby GNBP1 is involved in the hydrolysis of Gram-positive peptidoglycan producing new glycan reducing ends, which are subsequently detected by PGRP-SA. ..
- Tauszig Delamasure S, Bilak H, Capovilla M, Hoffmann J, Imler J. Drosophila MyD88 is required for the response to fungal and Gram-positive bacterial infections. Nat Immunol. 2002;3:91-7 pubmed..Phenotypic comparison of DmMyD88-mutant flies and MyD88-deficient mice showed essential differences in the control of Gram-negative infection in insects and mammals. ..
- Ayyaz A, Giammarinaro P, Liegeois S, Lestradet M, Ferrandon D. A negative role for MyD88 in the resistance to starvation as revealed in an intestinal infection of Drosophila melanogaster with the Gram-positive bacterium Staphylococcus xylosus. Immunobiology. 2013;218:635-44 pubmed publisher..Thus, we have uncovered a novel function of MyD88 in the regulation of metabolism that appears to be independent of its known roles in immunity and development. ..
- Castillejo Lopez C, Hacker U. The serine protease Sp7 is expressed in blood cells and regulates the melanization reaction in Drosophila. Biochem Biophys Res Commun. 2005;338:1075-82 pubmed
- Verma P, Tapadia M. Early gene Broad complex plays a key role in regulating the immune response triggered by ecdysone in the Malpighian tubules of Drosophila melanogaster. Mol Immunol. 2015;66:325-39 pubmed publisher..In the absence of ecdysone signaling the IMD pathway associated genes are down regulated and activation and translocation of transcription factor Relish is also affected. ..
- Leclerc V, Pelte N, El Chamy L, Martinelli C, Ligoxygakis P, Hoffmann J, et al. Prophenoloxidase activation is not required for survival to microbial infections in Drosophila. EMBO Rep. 2006;7:231-5 pubmed..This raises the question with regard to the precise function of phenoloxidase activation in defence, if any. ..
- Radyuk S, Michalak K, Klichko V, Benes J, Orr W. Peroxiredoxin 5 modulates immune response in Drosophila. Biochim Biophys Acta. 2010;1800:1153-63 pubmed publisher..Molecular and epistatic analyses identified dPrx5 as a negative regulator in the dTak1-JNK arm of immune signaling. Our findings suggest that peroxiredoxins play an important modulatory role in the Drosophila immune response. ..
- Ligoxygakis P, Pelte N, Hoffmann J, Reichhart J. Activation of Drosophila Toll during fungal infection by a blood serine protease. Science. 2002;297:114-6 pubmed..We show that ethylmethane sulfonate-induced mutations in the persephone gene, which encodes a previously unknown serine protease, block induction of the Toll pathway by fungi and resistance to this type of infection. ..
- Dionne M, Ghori N, Schneider D. Drosophila melanogaster is a genetically tractable model host for Mycobacterium marinum. Infect Immun. 2003;71:3540-50 pubmed..We believe that this system should be a useful genetically tractable model for mycobacterial infection...
- Khush -, Lemaitre -. Stop press: genes that fight infections: what the drosophila genome says about animal immunity. Trends Genet. 2000;16:468 pubmed
- Bonnay F, Nguyen X, Cohen Berros E, Troxler L, Batsche E, Camonis J, et al. Akirin specifies NF-ÎºB selectivity of Drosophila innate immune response via chromatin remodeling. EMBO J. 2014;33:2349-62 pubmed publisher..The discovery of this mechanism, conserved in mammals, paves the way for the establishment of more specific and less toxic anti-inflammatory drugs targeting pro-inflammatory genes. ..
- Delaney J, Stoven S, Uvell H, Anderson K, Engstrom Y, Mlodzik M. Cooperative control of Drosophila immune responses by the JNK and NF-kappaB signaling pathways. EMBO J. 2006;25:3068-77 pubmed..Our data indicate that dTAK1 is not required for Relish activation, but instead is required in JNK signaling for antimicrobial peptide gene expression. ..