Genomes and Genes
Gene Symbol: cact
Alias: 5848, BG:DS02740.15, CACT, CG5848, Cact, Cactus, Dmel\CG5848, Ikappa, NFkappabeta1A, cac, dip6, fs(2)ltoRN48, n(2)k17003, cactus, CG5848-PA, CG5848-PB, CG5848-PC, CG5848-PD, CG5848-PE, NF-kappa-B inhibitor cactus, cact-PA, cact-PB, cact-PC, cact-PD, cact-PE, female-sterile-(2)-ltoRN48
Species: fruit fly
- Stein D, Goltz J, Jurcsak J, Stevens L. The Dorsal-related immunity factor (Dif) can define the dorsal-ventral axis of polarity in the Drosophila embryo. Development. 1998;125:2159-69 pubmed
- Manfruelli P, Reichhart J, Steward R, Hoffmann J, Lemaitre B. A mosaic analysis in Drosophila fat body cells of the control of antimicrobial peptide genes by the Rel proteins Dorsal and DIF. EMBO J. 1999;18:3380-91 pubmed..Finally, we have used fat body cell clones homozygous for various mutations to show that a linear activation cascade Spaetzle--> Toll-->Cactus-->Dorsal/DIF leads to the induction of the drosomycin gene in larval fat body cells.
- Rutschmann S, Jung A, Hetru C, Reichhart J, Hoffmann J, Ferrandon D. The Rel protein DIF mediates the antifungal but not the antibacterial host defense in Drosophila. Immunity. 2000;12:569-80 pubmed..We discuss in this light the possibility that NF-KB1/p50 might be required more specifically in the innate immune response against gram-positive bacteria in mammals. ..
- 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..Thus, a yet to be identified IkappaB kinase complex must be required for Rel protein activation via the Toll signaling pathway. ..
- Isoda K, Roth S, Nusslein Volhard C. The functional domains of the Drosophila morphogen dorsal: evidence from the analysis of mutants. Genes Dev. 1992;6:619-30 pubmed..The nuclear uptake of the dl protein is stimulated by products of the dorsal group genes but inhibited by the cactus (cact) product...
- Qiu P, Pan P, Govind S. A role for the Drosophila Toll/Cactus pathway in larval hematopoiesis. Development. 1998;125:1909-20 pubmed..Mutations in cactus or Toll, or constitutive expression of dorsal can induce lamellocyte differentiation and cause the formation of ..
- Cornwell W, Kirkpatrick R. Cactus-independent nuclear translocation of Drosophila RELISH. J Cell Biochem. 2001;82:22-37 pubmed..In addition, loss of cactus expression via RNAi revealed that RELISH activation and nuclear translocation is not dependent on the presence of ..
- Fernandez N, Grosshans J, Goltz J, Stein D. Separable and redundant regulatory determinants in Cactus mediate its dorsal group dependent degradation. Development. 2001;128:2963-74 pubmed..of Dorsal, a Rel/NFkappaB homolog, is controlled by the interaction with its cognate IkappaB inhibitor protein Cactus, which is degraded on the ventral side of the embryo in response to dorsal group signaling...
- Sun H, Towb P, Chiem D, Foster B, Wasserman S. Regulated assembly of the Toll signaling complex drives Drosophila dorsoventral patterning. EMBO J. 2004;23:100-10 pubmed..Pelle to the MyD88-Tube complex promotes Pelle activation, leading to degradation of the IkappaB-like inhibitor, Cactus. Together, these experiments convert a linear picture of gene function into a dynamic mechanistic and structural ..
- Kidd S. Characterization of the Drosophila cactus locus and analysis of interactions between cactus and dorsal proteins. Cell. 1992;71:623-35 pubmed..One of these genes is the cactus locus, 1 of 11 genes required maternally for the establishment in embryos of a gradient of nuclear localization of ..
- Edwards D, Towb P, Wasserman S. An activity-dependent network of interactions links the Rel protein Dorsal with its cytoplasmic regulators. Development. 1997;124:3855-64 pubmed..signal relayed by Toll, Tube and Pelle releases the Rel-related protein Dorsal from its cytoplasmic inhibitor Cactus; free Dorsal translocates into nuclei and directs expression of ventral fates...
- Reach M, Galindo R, Towb P, Allen J, Karin M, Wasserman S. A gradient of cactus protein degradation establishes dorsoventral polarity in the Drosophila embryo. Dev Biol. 1996;180:353-64 pubmed..transduction via the protein kinase Pelle frees the Rel-related protein Dorsal from its cytoplasmic inhibitor Cactus, allowing Dorsal to translocate into ventral and ventrolateral nuclei and direct gene expression...
- Gillespie S, Wasserman S. Dorsal, a Drosophila Rel-like protein, is phosphorylated upon activation of the transmembrane protein Toll. Mol Cell Biol. 1994;14:3559-68 pubmed..that signal-dependent dorsal phosphorylation is modulated by three intracellular proteins, pelle, tube, and cactus. Using double-mutant embryos, we then explored the nature of the kinase activity responsible for dorsal ..
- Roth S, Hiromi Y, Godt D, Nusslein Volhard C. cactus, a maternal gene required for proper formation of the dorsoventral morphogen gradient in Drosophila embryos. Development. 1991;112:371-88 pubmed..Here we show that in contrast to the dorsal group genes, the maternal gene cactus acts as a negative regulator of the nuclear localization of the dorsal protein...
- Lemaitre B, Meister M, Govind S, Georgel P, Steward R, Reichhart J, et al. Functional analysis and regulation of nuclear import of dorsal during the immune response in Drosophila. EMBO J. 1995;14:536-45 pubmed..We also report that in mutants such as Toll or cactus, which exhibit melanotic tumor phenotypes, dl is constitutively nuclear...
- Heckscher E, Fetter R, Marek K, Albin S, Davis G. NF-kappaB, IkappaB, and IRAK control glutamate receptor density at the Drosophila NMJ. Neuron. 2007;55:859-73 pubmed..Here, we show that the NF-kappaB and IkappaB homologs Dorsal and Cactus surround postsynaptic glutamate receptor (GluR) clusters at the Drosophila NMJ...
- Belvin M, Jin Y, Anderson K. Cactus protein degradation mediates Drosophila dorsal-ventral signaling. Genes Dev. 1995;9:783-93 pubmed..b>Cactus, like its mammalian homolog I kappa B, inhibits nuclear translocation by binding Dorsal and retaining it in the ..
- Dolezal T, Dolezelova E, Zurovec M, Bryant P. A role for adenosine deaminase in Drosophila larval development. PLoS Biol. 2005;3:e201 pubmed..The existence of such an independent mechanism has also been suggested in mammals. ..
- Govind S, Brennan L, Steward R. Homeostatic balance between dorsal and cactus proteins in the Drosophila embryo. Development. 1993;117:135-48 pubmed..The dorsal protein is cytoplasmic in early embryos, possibly because of a direct interaction with cactus. In response to a ventral signal, dorsal protein becomes partitioned into nuclei of cleavage-stage syncytial ..
- Cantera R, Kozlova T, Barillas Mury C, Kafatos F. Muscle structure and innervation are affected by loss of Dorsal in the fruit fly, Drosophila melanogaster. Mol Cell Neurosci. 1999;13:131-41 pubmedIn Drosophila, the Rel-protein Dorsal and its inhibitor, Cactus, act in signal transduction pathways that control the establishment of dorsoventral polarity during embryogenesis and the immune response during postembryonic life...
- Belvin M, Anderson K. A conserved signaling pathway: the Drosophila toll-dorsal pathway. Annu Rev Cell Dev Biol. 1996;12:393-416 pubmed..Pelle activity controls the degradation of the Cactus protein, which is present in a cytoplasmic complex with the Dorsal protein...
- Sorrentino R, Melk J, Govind S. Genetic analysis of contributions of dorsal group and JAK-Stat92E pathway genes to larval hemocyte concentration and the egg encapsulation response in Drosophila. Genetics. 2004;166:1343-56 pubmed
- Hoffmann J, Kafatos F, Janeway C, Ezekowitz R. Phylogenetic perspectives in innate immunity. Science. 1999;284:1313-8 pubmed..In addition to its role in the early phase of defense, innate immunity in mammals appears to play a key role in stimulating the subsequent, clonal response of adaptive immunity. ..
- Drier E, Huang L, Steward R. Nuclear import of the Drosophila Rel protein Dorsal is regulated by phosphorylation. Genes Dev. 1999;13:556-68 pubmed..Dorsal is retained in the cytoplasm by the IkappaB protein, Cactus. Signal-dependent phosphorylation of Cactus results in the degradation of Cactus and the nuclear targeting of ..
- Whalen A, Steward R. Dissociation of the dorsal-cactus complex and phosphorylation of the dorsal protein correlate with the nuclear localization of dorsal. J Cell Biol. 1993;123:523-34 pubmed..This process is regulated by the action of the dorsal group genes and cactus. We show that dorsal and cactus are both phosphoproteins that form a stable cytoplasmic complex, and that the ..
- Fontenele M, Carneiro K, Agrellos R, Oliveira D, Oliveira Silva A, Vieira V, et al. The Ca2+-dependent protease Calpain A regulates Cactus/I kappaB levels during Drosophila development in response to maternal Dpp signals. Mech Dev. 2009;126:737-51 pubmed publisher..Toll pathway directs Dorsal nuclear translocation by inducing proteosomal degradation of the I kappaB homologue Cactus. Another mechanism that impacts on Dorsal activation involves the Toll-independent pathway, which regulates ..
- Govind S. Rel signalling pathway and the melanotic tumour phenotype of Drosophila. Biochem Soc Trans. 1996;24:39-44 pubmed
- Bergmann A, Stein D, Geisler R, Hagenmaier S, Schmid B, Fernandez N, et al. A gradient of cytoplasmic Cactus degradation establishes the nuclear localization gradient of the dorsal morphogen in Drosophila. Mech Dev. 1996;60:109-23 pubmed..Two of these genes, dorsal and cactus, show homology to the mammalian transcription factor NF-kappa B and its inhibitor I kappa B, respectively...
- Chiu H, Ring B, Sorrentino R, Kalamarz M, Garza D, Govind S. dUbc9 negatively regulates the Toll-NF-kappa B pathways in larval hematopoiesis and drosomycin activation in Drosophila. Dev Biol. 2005;288:60-72 pubmed..of the Rel/NF-kappaB-family transcription factors Dorsal and Dif or in the presence of a non-signaling allele of Cactus, the IkappaB protein in Drosophila...
- Braun A, Hoffmann J, Meister M. Analysis of the Drosophila host defense in domino mutant larvae, which are devoid of hemocytes. Proc Natl Acad Sci U S A. 1998;95:14337-42 pubmed..By working in synergy, they provide Drosophila a highly effective defense against injury and/or infection...
- Lehming N, Thanos D, Brickman J, Ma J, Maniatis T, Ptashne M. An HMG-like protein that can switch a transcriptional activator to a repressor. Nature. 1994;371:175-9 pubmed..Thus, the HMG-like proteins DSP1 and HMG I(Y) can determine whether a specific regulator functions as an activator or a repressor of transcription. ..
- 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. ..
- Lanot R, Zachary D, Holder F, Meister M. Postembryonic hematopoiesis in Drosophila. Dev Biol. 2001;230:243-57 pubmed..Cells within all lymph gland lobes, including prohemocytes from posterior lobes, massively differentiate into a new cell type specifically devoted to encapsulation, the lamellocyte. ..
- Lehming N, McGuire S, Brickman J, Ptashne M. Interactions of a Rel protein with its inhibitor. Proc Natl Acad Sci U S A. 1995;92:10242-6 pubmedb>Cactus, a Drosophila homologue of I kappa B, binds to and inhibits Dorsal, a homologue of the p50 and p65 components of NF-kappa B...
- Lehmann M, Jiang C, Ip Y, Thummel C. AP-1, but not NF-kappa B, is required for efficient steroid-triggered cell death in Drosophila. Cell Death Differ. 2002;9:581-90 pubmed..This study demonstrates a role for AP-1 in the stage-specific steroid-triggered programmed cell death of larval tissues during Drosophila metamorphosis. ..
- 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. ..
- 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. ..
- 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. ..
- Packman L, Kubota K, Parker J, Gay N. Casein kinase II phosphorylates Ser468 in the PEST domain of the Drosophila IkappaB homologue cactus. FEBS Lett. 1997;400:45-50 pubmedb>Cactus protein is a Drosophila homologue of the mammalian IkappaB family of cytoplasmic anchor proteins...
- Isoda K, Nusslein Volhard C. Disulfide cross-linking in crude embryonic lysates reveals three complexes of the Drosophila morphogen dorsal and its inhibitor cactus. Proc Natl Acad Sci U S A. 1994;91:5350-4 pubmed..b>cactus (cact) represses the nuclear localization of dl protein...
- Drier E, Govind S, Steward R. Cactus-independent regulation of Dorsal nuclear import by the ventral signal. Curr Biol. 2000;10:23-6 pubmed..During early Drosophila development, the Toll-Cactus-Dorsal pathway regulates the establishment of the embryonic dorsoventral axis...
- Lemaitre B, Nicolas E, Michaut L, Reichhart J, Hoffmann J. The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell. 1996;86:973-83 pubmed..of the morphogen dorsal in Drosophila embryos show striking structural and functional similarities (Toll/IL-1, Cactus/I-kappaB, and dorsal/NF-kappaB)...
- Cantera R, Roos E, Engstrom Y. Dif and cactus are colocalized in the larval nervous system of Drosophila melanogaster. J Neurobiol. 1999;38:16-26 pubmed..animals, Dif is normally located in the cytoplasm, most likely in a complex with an IkappaB molecule such as Cactus. Upon infection, Dif is enriched in the nucleus of immunoresponsive tissues such as fat body and blood cells...
- Scuderi A, Simin K, Kazuko S, Metherall J, Letsou A. scylla and charybde, homologues of the human apoptotic gene RTP801, are required for head involution in Drosophila. Dev Biol. 2006;291:110-22 pubmed
- Lau G, Goumnerov B, Walendziewicz C, Hewitson J, Xiao W, Mahajan Miklos S, et al. The Drosophila melanogaster toll pathway participates in resistance to infection by the gram-negative human pathogen Pseudomonas aeruginosa. Infect Immun. 2003;71:4059-66 pubmed..In contrast, a constitutively active Toll mutant and a loss-of-function mutant of Cactus, an I kappa B-like factor that inhibits the Toll signaling, reduce infectivity...
- Fukui A, Inaki M, Tonoe G, Hamatani H, Homma M, Morimoto T, et al. Lola regulates glutamate receptor expression at the Drosophila neuromuscular junction. Biol Open. 2012;1:362-75 pubmed publisher..The transcriptional level of lola, in turn, is downregulated by increased neural activity. We propose that Lola coordinates expression of multiple postsynaptic components by transcriptional regulation. ..
- Ahmad S, Sweeney S, Lee J, Sweeney N, Gao F. Genetic screen identifies serpin5 as a regulator of the toll pathway and CHMP2B toxicity associated with frontotemporal dementia. Proc Natl Acad Sci U S A. 2009;106:12168-73 pubmed publisher..This fly model will be useful to further dissect genetic pathways that are potentially relevant to the pathogenesis and treatment of FTD. ..
- Mathey Prevot B, Perrimon N. Mammalian and Drosophila blood: JAK of all trades?. Cell. 1998;92:697-700 pubmed
- Kwiatkowski D. The complexity of genetic variation in a simple immune system. Trends Genet. 2005;21:197-9 pubmed..However, the effects of individual polymorphisms on the resistance phenotype were modest, and epistatic interactions appeared to be common. What might these findings tell us about genetic resistance to infection in humans? ..
- Gaasterland T, Sczyrba A, Thomas E, Aytekin Kurban G, Gordon P, Sensen C. MAGPIE/EGRET annotation of the 2.9-Mb Drosophila melanogaster Adh region. Genome Res. 2000;10:502-10 pubmed..The software modules that add eukaryotic genome annotation capability to MAGPIE are available as EGRET (Eukaryotic Genome Rapid Evaluation Tool). ..
- Markovic M, Kylsten P, Dushay M. Drosophila lamin mutations cause melanotic mass formation and lamellocyte differentiation. Mol Immunol. 2009;46:3245-50 pubmed publisher..Lamins thus affect immunity in Drosophila, and lam mutations can serve as genetic tools to dissect cellular immune signaling and effector pathways. ..
- Carroll S, Winslow G, Twombly V, Scott M. Genes that control dorsoventral polarity affect gene expression along the anteroposterior axis of the Drosophila embryo. Development. 1987;99:327-32 pubmed
- Govind S, Steward R. Gene regulation: coming to grips with cactus. Curr Biol. 1993;3:351-4 pubmed
- Engstrom Y, Kadalayil L, Sun S, Samakovlis C, Hultmark D, Faye I. kappa B-like motifs regulate the induction of immune genes in Drosophila. J Mol Biol. 1993;232:327-33 pubmed..Our data suggest a functional and evolutionary relationship between these insect immune response factors and the mammalian NF-kappa B. ..
- Petersen A, Katzenberger R, Wassarman D. The innate immune response transcription factor relish is necessary for neurodegeneration in a Drosophila model of ataxia-telangiectasia. Genetics. 2013;194:133-42 pubmed publisher..In summary, these findings suggest that neurodegeneration in human A-T is caused by activation of a specific NF-?B protein in glial cells. ..
- Loya C, McNeill E, Bao H, Zhang B, Van Vactor D. miR-8 controls synapse structure by repression of the actin regulator enabled. Development. 2014;141:1864-74 pubmed publisher..Together, these findings suggest that miR-8 limits the expansion of presynaptic terminals during larval synapse development through regulation of postsynaptic actin assembly that is independent of changes in synapse physiology. ..
- Zhou B, Lindsay S, Wasserman S. Alternative NF-ÎºB Isoforms in the Drosophila Neuromuscular Junction and Brain. PLoS ONE. 2015;10:e0132793 pubmed publisher..We find that Dorsal B interacts with and stabilizes Cactus at the neuromuscular junction, but exhibits Cactus independent localization and an absence of detectable nuclear ..
- Gordon M, Dionne M, Schneider D, Nusse R. WntD is a feedback inhibitor of Dorsal/NF-kappaB in Drosophila development and immunity. Nature. 2005;437:746-9 pubmed..and increased levels of WntD block Dorsal nuclear accumulation, even in the absence of the IkappaB homologue Cactus. The WntD signal is independent of the common Wnt signalling component Armadillo (beta-catenin)...
- Cao C, Liu Y, Lehmann M. Fork head controls the timing and tissue selectivity of steroid-induced developmental cell death. J Cell Biol. 2007;176:843-52 pubmed..More generally, they suggest that cell identity factors like Fkh play a pivotal role in the normal control of developmental cell death. ..
- van Uden P, Kenneth N, Webster R, MÃ¼ller H, Mudie S, Rocha S. Evolutionary conserved regulation of HIF-1Î² by NF-ÎºB. PLoS Genet. 2011;7:e1001285 pubmed publisher..These results reveal a novel mechanism of HIF regulation, with impact in the development of novel therapeutic strategies for HIF-related pathologies including ageing, ischemia, and cancer. ..
- Ray R, Arora K, Nusslein Volhard C, Gelbart W. The control of cell fate along the dorsal-ventral axis of the Drosophila embryo. Development. 1991;113:35-54 pubmed..Two of the genes, dpp and twi, are unaffected by mutations in any of the tested zygotic dorsal-ventral genes, suggesting that dpp and twi are the primary patterning genes for dorsal ectoderm and mesoderm, respectively...
- Minakhina S, Yang J, Steward R. Tamo selectively modulates nuclear import in Drosophila. Genes Cells. 2003;8:299-310 pubmed..Tamo has an essential function during oogenesis. Tamo interacts with Dorsal and proteins that are part of the nuclear import machinery. We propose that tamo modulates the levels of import of Dorsal and other proteins. ..