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Gene Review

cact  -  cactus

Drosophila melanogaster

Synonyms: 5848, BG:DS02740.15, CACT, CG5848, Cact, ...
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High impact information on cact

  • The cytokine-induced activation cascade of NF-kappaB in mammals and the activation of the morphogen dorsal in Drosophila embryos show striking structural and functional similarities (Toll/IL-1, Cactus/I-kappaB, and dorsal/NF-kappaB) [1].
  • Therefore the two signalling pathways that target Cactus for degradation must discriminate between Cactus-Dorsal and Cactus-Dif complexes [2].
  • We conclude that the formation of a wild-type Dorsal nuclear gradient requires the phosphorylation of both Cactus and Dorsal [3].
  • We find that Dorsal is phosphorylated by the ventral signal while associated with Cactus, and that Dorsal phosphorylation is essential for its nuclear import [3].
  • Regulated proteolysis of Cactus, the cytoplasmic inhibitor of the Rel-related transcription factor Dorsal, is an essential step in patterning of the Drosophila embryo [4].

Biological context of cact

  • The proteins truncated at the carboxy-terminal end show increased levels of nuclear uptake dorsally, but they still respond to the cact-mediated inhibition of nuclear transport [5].
  • Here, we provide evidence that maternal Sog and Dpp proteins are secreted into the perivitelline space where they remain until early embryogenesis to modulate Cactus degradation, enabling their dual function in patterning the eggshell and embryo [6].
  • The Drosophila Rel transcription factor Dorsal and its inhibitor Cactus participate in a signal transduction pathway involved in several biologic processes, including embryonic pattern formation, immunity, and muscle development [7].
  • The phenotype of homozygous dorsal mutant larvae suggested that Dorsal and Cactus maybe necessary for normal function and maintenance of the neuromuscular system [7].
  • Signal-induced Cactus degradation frees Dorsal for nuclear translocation on the ventral and lateral sides of the embryo, establishing zones of gene expression along the dorsoventral axis [4].

Anatomical context of cact

  • Here, we have studied the regulation of the IkappaB homologue Cactus in the fat body during the immune response [8].
  • Synaptic activity modifies the levels of Dorsal and Cactus at the neuromuscular junction of Drosophila [7].
  • In blastoderm cells and immune competent cells, Cactus inhibits Dorsal and Dif by preventing their nuclear localization [9].
  • Analysis of cactus mutants that lack Cactus protein revealed that almost all of these animals have an overabundance of hemocytes, carry melanotic capsules and die before reaching pupal stages [10].
  • Here, we demonstrate that both Dif and Cactus are expressed in the central nervous system (CNS) of Drosophila [11].

Associations of cact with chemical compounds

  • Using larval body wall preparations and antibodies specific for Dorsal or Cactus we show that the amount of these proteins at the neuromuscular junction is substantially decreased after electrical stimulation of the nerves or incubation in glutamate, the principal transmitter in this type of synapse [7].
  • Conversion of these serines to alanine or glutamic acid residues differentially affects the levels and activity of Cactus in embryos, but does not inhibit the binding of Cactus to Dorsal [4].
  • In a two-hybrid screen for additional components of the pathway using the Drosophila I-kappaB protein Cactus as a bait, we isolated a novel coiled-coil protein with N-terminal Arg-Asp (RD)- like motifs that we call Cactin [12].
  • Genetic analyses of Dorsal have defined components of a signaling pathway for Dorsal activation, including a serine/threonine kinase, Pelle, placed upstream of Dorsal and Cactus [13].

Physical interactions of cact

  • DLAK-bound Cactus can be degraded in a LPS signal-dependent fashion, whereas the DLAK(K50A) mutant-bound Cactus is completely resistant to degradation in the presence of LPS [14].
  • Complex 3 (200 kDa) is a cact protein complex that does not contain dl protein [15].
  • Tube and Pelle then transduce the signal from activated Toll to a complex of Dorsal and Cactus [16].

Regulatory relationships of cact

  • The nuclear uptake of the dl protein is stimulated by products of the dorsal group genes but inhibited by the cactus (cact) product [5].
  • Overexpression of dominant-negative mutant DLAK (DLAK(K50A)) blocks LPS-induced Cactus degradation [14].
  • Phosphorylation of both Dorsal and Cactus is regulated by a Toll-receptor-dependent ventral signal relayed by the Tube and Pelle proteins [17].

Other interactions of cact

  • Therefore, carboxy-terminal sequences influence the cytoplasmic retention, although a domain of dl-cact interaction residues in the amino-terminal portion [5].
  • Signaling through the maternal BMP pathway also alters the dorsal gradient, probably by regulating degradation of the IkB homologue Cactus [6].
  • Signaling through these components directs degradation of the IkappaB-like inhibitor Cactus and nuclear translocation of the Rel protein Dorsal [18].
  • Cactus, Dorsal and Dif are also expressed in somatic muscles, where Cactus and Dorsal, but not Dif, are enriched at the neuromuscular junction [9].
  • We also observed that the inhibition of the calcium dependent protein phosphatase calcineurin prevents the effect of glutamate on the fluorescence for Dorsal and Cactus, suggesting its participation in a signal transduction cascade that may activate Dorsal in the muscle independently of Toll [7].

Analytical, diagnostic and therapeutic context of cact

  • Here, we extracted RNA from adult flies and revealed, by RT-PCR and restriction-enzyme analyses, that transcript heterogeneity exists in vivo for three distinct edited sites within the cac-encoded RNA [19].


  1. The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Lemaitre, B., Nicolas, E., Michaut, L., Reichhart, J.M., Hoffmann, J.A. Cell (1996) [Pubmed]
  2. Regulated nuclear import of Rel proteins in the Drosophila immune response. Wu, L.P., Anderson, K.V. Nature (1998) [Pubmed]
  3. Nuclear import of the Drosophila Rel protein Dorsal is regulated by phosphorylation. Drier, E.A., Huang, L.H., Steward, R. Genes Dev. (1999) [Pubmed]
  4. A role for CKII phosphorylation of the cactus PEST domain in dorsoventral patterning of the Drosophila embryo. Liu, Z.P., Galindo, R.L., Wasserman, S.A. Genes Dev. (1997) [Pubmed]
  5. The functional domains of the Drosophila morphogen dorsal: evidence from the analysis of mutants. Isoda, K., Roth, S., Nüsslein-Volhard, C. Genes Dev. (1992) [Pubmed]
  6. Graded maternal short gastrulation protein contributes to embryonic dorsal-ventral patterning by delayed induction. Carneiro, K., Fontenele, M., Negreiros, E., Lopes, E., Bier, E., Araujo, H. Dev. Biol. (2006) [Pubmed]
  7. Synaptic activity modifies the levels of Dorsal and Cactus at the neuromuscular junction of Drosophila. Bolatto, C., Chifflet, S., Megighian, A., Cantera, R. J. Neurobiol. (2003) [Pubmed]
  8. In vivo regulation of the IkappaB homologue cactus during the immune response of Drosophila. Nicolas, E., Reichhart, J.M., Hoffmann, J.A., Lemaitre, B. J. Biol. Chem. (1998) [Pubmed]
  9. The inhibitor kappaB-ortholog Cactus is necessary for normal neuromuscular function in Drosophila melanogaster. Beramendi, A., Peron, S., Megighian, A., Reggiani, C., Cantera, R. Neuroscience (2005) [Pubmed]
  10. A role for the Drosophila Toll/Cactus pathway in larval hematopoiesis. Qiu, P., Pan, P.C., Govind, S. Development (1998) [Pubmed]
  11. Dif and cactus are colocalized in the larval nervous system of Drosophila melanogaster. Cantera, R., Roos, E., Engström, Y. J. Neurobiol. (1999) [Pubmed]
  12. Cactin, a conserved protein that interacts with the Drosophila IkappaB protein cactus and modulates its function. Lin, P., Huang, L.H., Steward, R. Mech. Dev. (2000) [Pubmed]
  13. Developmental and tissue-specific expression of mouse pelle-like protein kinase. Trofimova, M., Sprenkle, A.B., Green, M., Sturgill, T.W., Goebl, M.G., Harrington, M.A. J. Biol. Chem. (1996) [Pubmed]
  14. Lipopolysaccharide-activated kinase, an essential component for the induction of the antimicrobial peptide genes in Drosophila melanogaster cells. Kim, Y.S., Han, S.J., Ryu, J.H., Choi, K.H., Hong, Y.S., Chung, Y.H., Perrot, S., Raibaud, A., Brey, P.T., Lee, W.J. J. Biol. Chem. (2000) [Pubmed]
  15. Disulfide cross-linking in crude embryonic lysates reveals three complexes of the Drosophila morphogen dorsal and its inhibitor cactus. Isoda, K., Nüsslein-Volhard, C. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  16. Recruitment of Tube and Pelle to signaling sites at the surface of the Drosophila embryo. Towb, P., Galindo, R.L., Wasserman, S.A. Development (1998) [Pubmed]
  17. Cactus-independent regulation of Dorsal nuclear import by the ventral signal. Drier, E.A., Govind, S., Steward, R. Curr. Biol. (2000) [Pubmed]
  18. The protein kinase Pelle mediates feedback regulation in the Drosophila Toll signaling pathway. Towb, P., Bergmann, A., Wasserman, S.A. Development (2001) [Pubmed]
  19. RNA editing in the Drosophila DMCA1A calcium-channel alpha 1 subunit transcript. Smith, L.A., Peixoto, A.A., Hall, J.C. J. Neurogenet. (1998) [Pubmed]
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