IKKbeta

Summary

Gene Symbol: IKKbeta
Description: I-kappaB kinase beta
Alias: CG4201, DIK, DLAK, DmIKK, DmIKKBeta, DmIKKb, DmIKKbeta, DmIkkbeta, Dmel\CG4201, Dmikkb, Dmikkbeta, IKK, IKK-beta, IKKB, IKKb, IRD-5, IRD5, Ikkb, Ikkbeta, Ird-5, Ird5, LRK, Lak, anon-89Bd, dIKK, dIKK-beta, dIKKbeta, dLak, dmIKKbeta, ikk, ird, ird-5, ird5, ird5/DmIkk[beta], ird[5], I-kappaB kinase beta, CG4201-PB, IKK-like protein, IKKbeta-PB, LPS-responsive kinase, LPS-responsive-kinase, cactus kinase, immune response deficient 5, immune response-deficient 5, lipopolysaccharide activated kinase, mmune response deficient 5
Species: fruit fly

Top Publications

  1. 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 pubmed
    Here we report the identification of a Drosophila IkappaB kinase complex containing DmIKKbeta and DmIKKgamma, homologs of the human IKKbeta and IKKgamma proteins...
  2. 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. ..
  3. 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...
  4. 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 show that imd functions upstream of the DmIKK signalosome and the caspase DREDD in the control of antibacterial peptide genes...
  5. 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. ..
  6. 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. ..
  7. 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. ..
  8. Meinander A, Runchel C, Tenev T, Chen L, Kim C, Ribeiro P, et al. Ubiquitylation of the initiator caspase DREDD is required for innate immune signalling. EMBO J. 2012;31:2770-83 pubmed publisher
    ..The direct involvement of ubiquitylation in caspase activation represents a novel mechanism for non-apoptotic caspase-mediated signalling. ..
  9. 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...

More Information

Publications44

  1. Lu Y, Wu L, Anderson K. The antibacterial arm of the drosophila innate immune response requires an IkappaB kinase. Genes Dev. 2001;15:104-10 pubmed
    The ird5 gene was identified in a genetic screen for Drosophila immune response mutants...
  2. Choe K, Werner T, Stoven S, Hultmark D, Anderson K. Requirement for a peptidoglycan recognition protein (PGRP) in Relish activation and antibacterial immune responses in Drosophila. Science. 2002;296:359-62 pubmed
  3. 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. ..
  4. 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. ..
  5. 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. ..
  6. Bandarra D, Biddlestone J, Mudie S, Müller H, Rocha S. HIF-1α restricts NF-κB-dependent gene expression to control innate immunity signals. Dis Model Mech. 2015;8:169-81 pubmed publisher
    ..HIF-1α depletion enhances the NF-κB response, and this required not only the TAK-IKK complex, but also CDK6...
  7. 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. ..
  8. 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. ..
  9. Bergmann A. IKK epsilon signaling: not just NF-kappaB. Curr Biol. 2006;16:R588-90 pubmed
    ..Surprisingly, three recent reports implicate IKKs in Drosophila in seemingly unrelated functions, including non-apoptotic caspase activation and cytoskeleton organization. ..
  10. 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. ..
  11. Jasper H, Bohmann D. Drosophila innate immunity: a genomic view of pathogen defense. Mol Cell. 2002;10:967-9 pubmed
  12. Cullen C, Deak P, Glover D, Ohkura H. mini spindles: A gene encoding a conserved microtubule-associated protein required for the integrity of the mitotic spindle in Drosophila. J Cell Biol. 1999;146:1005-18 pubmed
    ..The absence of centrosomal staining in interphase of the cellularized embryos suggests that the interactions between Msps protein and microtubules or centrosomes may be regulated during the cell cycle. ..
  13. Huang H, Chen Z, Kunes S, Chang G, Maniatis T. Endocytic pathway is required for Drosophila Toll innate immune signaling. Proc Natl Acad Sci U S A. 2010;107:8322-7 pubmed publisher
    ..Mop and Hrs, which are critical components of the ESCRT-0 endocytosis complex, colocalize with the Toll receptor in endosomes. We conclude that endocytosis is required for the activation of the Toll signaling pathway. ..
  14. Khush R, Leulier F, Lemaitre B. Immunology. Pathogen surveillance--the flies have it. Science. 2002;296:273-5 pubmed
  15. Davis M, Primrose D, Hodgetts R. A member of the p38 mitogen-activated protein kinase family is responsible for transcriptional induction of Dopa decarboxylase in the epidermis of Drosophila melanogaster during the innate immune response. Mol Cell Biol. 2008;28:4883-95 pubmed publisher
    ..We propose that the involvement of DDC in a new pathway involved in Drosophila immunity increases the levels of dopamine, which is metabolized to produce reactive quinones that exert an antimicrobial effect on invading bacteria. ..
  16. Aparicio R, Neyen C, Lemaitre B, Busturia A. dRYBP contributes to the negative regulation of the Drosophila Imd pathway. PLoS ONE. 2013;8:e62052 pubmed publisher
    ..Beyond the identification of dRYBP as a novel component of Imd pathway regulation, our results also suggest that the evolutionarily conserved RYBP protein may be involved in the human innate immune response. ..
  17. 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. ..
  18. Kanao T, Sawada T, Davies S, Ichinose H, Hasegawa K, Takahashi R, et al. The nitric oxide-cyclic GMP pathway regulates FoxO and alters dopaminergic neuron survival in Drosophila. PLoS ONE. 2012;7:e30958 pubmed publisher
    ..These results strongly suggest that the NO-FoxO axis contributes to DA neurodegeneration in LRRK2-linked PD. ..
  19. Bandarra D, Biddlestone J, Mudie S, Müller H, Rocha S. Hypoxia activates IKK-NF-κB and the immune response in Drosophila melanogaster. Biosci Rep. 2014;34: pubmed publisher
    ..Here we show that hypoxia activates the IKK-NF-κB [IκB (inhibitor of nuclear factor κB)-NF-κB] pathway and the immune response in Drosophila ..
  20. Dijkers P, O Farrell P. Drosophila calcineurin promotes induction of innate immune responses. Curr Biol. 2007;17:2087-93 pubmed
    ..Thus, CanA1 provides an additional input into Relish-promoted immune responses and functions in hemocytes to promote a tissue-to-tissue signaling cascade required for robust immune response. ..
  21. Peng J, Zipperlen P, Kubli E. Drosophila sex-peptide stimulates female innate immune system after mating via the Toll and Imd pathways. Curr Biol. 2005;15:1690-4 pubmed
    ..Mating may physically damage females and pathogens may be transferred. Thus, endogenous stimulation of AMP transcription by SP at mating might be considered as a preventive step to encounter putative immunogenic attacks. ..
  22. Liu X, Sano T, Guan Y, Nagata S, Hoffmann J, Fukuyama H. Drosophila EYA regulates the immune response against DNA through an evolutionarily conserved threonine phosphatase motif. PLoS ONE. 2012;7:e42725 pubmed publisher
    ..Furthermore EYA associates with IKK? and full-length RELISH, and the induction of the IMD pathway-dependent antimicrobial peptide gene is independent ..
  23. 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. ..
  24. Verma P, Tapadia M. Epithelial immune response in Drosophila malpighian tubules: interplay between Diap2 and ion channels. J Cell Physiol. 2014;229:1078-95 pubmed publisher
    ..Thus Diap2 seems to be a key regulator of epithelial immune response in MTs, perhaps by modulating ion channels. ..
  25. 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. ..
  26. 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. ..
  27. 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. ..
  28. Cully M, Genevet A, Warne P, Treins C, Liu T, Bastien J, et al. A role for p38 stress-activated protein kinase in regulation of cell growth via TORC1. Mol Cell Biol. 2010;30:481-95 pubmed publisher
    ..These data suggest that p38 is an important positive regulator of TORC1 in both mammalian and Drosophila systems in response to certain stresses and growth factors. ..
  29. 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. ..
  30. Kim Y, Han S, Ryu J, Choi K, Hong Y, Chung Y, et al. Lipopolysaccharide-activated kinase, an essential component for the induction of the antimicrobial peptide genes in Drosophila melanogaster cells. J Biol Chem. 2000;275:2071-9 pubmed
    ..Here we have cloned a novel Drosophila LPS-activated kinase (DLAK) that is structurally related to mammalian IkappaB kinases...
  31. Vonkavaara M, Telepnev M, Ryden P, Sjostedt A, Stoven S. Drosophila melanogaster as a model for elucidating the pathogenicity of Francisella tularensis. Cell Microbiol. 2008;10:1327-38 pubmed publisher
    ..melanogaster is a suitable model for the analysis of interactions between F. tularensis and its arthropod hosts and that it can also be used to identify F. tularensis virulence factors relevant for mammalian hosts. ..
  32. Khush -, Lemaitre -. Stop press: genes that fight infections: what the drosophila genome says about animal immunity. Trends Genet. 2000;16:468 pubmed
  33. Govind S, Nehm R. Innate immunity in fruit flies: a textbook example of genomic recycling. PLoS Biol. 2004;2:E276 pubmed
  34. Dobson A, Chaston J, Newell P, Donahue L, Hermann S, Sannino D, et al. Host genetic determinants of microbiota-dependent nutrition revealed by genome-wide analysis of Drosophila melanogaster. Nat Commun. 2015;6:6312 pubmed publisher
    ..These interactions with the microbiota are probably conserved across animals, including humans. ..
  35. Wu L, Anderson K. Regulated nuclear import of Rel proteins in the Drosophila immune response. Nature. 1998;392:93-7 pubmed
    ..Mutations in three other genes cause constitutive nuclear localization of Dif; these mutations may block Rel protein activity by a novel mechanism. ..