Cactus is the Drosophila member of the IkappaB family of NF-kappaB inhibitors. It is a cytoplasmic ankyrin-repeat protein that binds the Rel-family transcription factors Dorsal and Dif, masking their DNA-binding and nuclear-localization functions and retaining them in the cytoplasm. Activation of the Toll receptor by cleaved Spaetzle leads, via the MyD88-Tube-Pelle complex, to Pelle-mediated phosphorylation of N-terminal signal-responsive serines in Cactus and its Slimb (betaTrCP)-dependent proteasomal degradation, releasing Dorsal/Dif to enter nuclei. A separate, signal-independent turnover pathway acts through the C-terminal PEST region. Maternally, a ventral-to-dorsal gradient of Cactus degradation shapes the nuclear Dorsal gradient that patterns the embryonic dorsoventral axis; loss of cactus ventralizes and stabilized alleles dorsalize embryos. In larvae and adults Cactus restrains Toll-dependent antifungal and anti-Gram-positive antimicrobial peptide gene expression, and its own transcription is induced by Toll signaling as negative feedback. Cactus also regulates prohemocyte differentiation in the lymph gland and accumulates with Dorsal at the postsynaptic side of larval neuromuscular junctions.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0002789 negative regulation of antifungal peptide production | IMP PMID:10369678 A mosaic analysis in Drosophila fat body cells of the contro... | ACCEPT | Summary: Cactus acts in fat body cells as the inhibitor in the Spaetzle-Toll-Cactus-Dorsal/DIF cascade that controls induction of the antifungal peptide gene drosomycin; loss of cactus derepresses drosomycin. Reason: Mosaic analysis in larval fat body places Cactus as the negative element of the linear cascade controlling drosomycin induction. Cactus holds Dorsal/DIF in the cytoplasm, so it directly limits antifungal peptide gene expression; the regulatory term is appropriate. Supporting Evidence: PMID:10369678 a linear activation cascade Spaetzle--> Toll-->Cactus-->Dorsal/DIF leads to the induction of the drosomycin gene in larval fat body cells |
| GO:0002789 negative regulation of antifungal peptide production | IMP PMID:8808632 The dorsoventral regulatory gene cassette spΓ€tzle/Toll/cactu... | ACCEPT | Summary: The spz/Toll/cactus cassette controls the drosomycin antifungal response in adults; cactus loss-of-function derepresses drosomycin. Reason: Classic genetic evidence that Cactus is the intracellular negative regulator of the Toll-dependent antifungal peptide response (PMID:8808632); consistent with its IkappaB sequestering mechanism. Supporting Evidence: PMID:8808632 the intracellular components of the dorsoventral signaling pathway (except for dorsal) and the extracellular Toll ligand PMID:24086459 Cactus, a fly IΞΊB protein, is the inhibitor for both Dif and Dorsal. |
| GO:0005515 protein binding | IPI PMID:10636911 Lipopolysaccharide-activated kinase, an essential component ... | REMOVE | Summary: Cactus interacts with and is phosphorylated in vitro by IKKbeta (DLAK) in LPS-stimulated cells. Reason: Generic protein binding is uninformative; here Cactus is the kinase substrate. Later work showed that the Drosophila IKK does not function in the Toll pathway and that Pelle is the Cactus kinase, so this interaction does not define a Cactus activity. Removal does not dispute the reported interaction. Supporting Evidence: PMID:10636911 DLAK can interact with Cactus, a Drosophila IkappaB and phosphorylate recombinant Cactus, in vitro. PMID:24086459 Surprisingly, the Drosophila IKK does not function in the fly Toll pathway |
| GO:0005515 protein binding | IPI PMID:10842059 Cactin, a conserved protein that interacts with the Drosophi... | MODIFY | Summary: IPI for Cactus binding Dorsal (P15330), recorded against the cactin paper. Reason: The listed partner is Dorsal, a Rel/NF-kappaB transcription factor. Cactus-Dorsal binding is well established (PMID:7479760, PMID:7705656). The cached abstract of PMID:10842059 describes the cactin screen; the curator had the full text. Replace uninformative protein binding with NF-kappaB binding. Proposed replacements: NF-kappaB binding Supporting Evidence: PMID:7479760 Cactus, a Drosophila homologue of I kappa B, binds to and inhibits Dorsal PMID:7705656 Cactus, like its mammalian homolog I kappa B, inhibits nuclear translocation by binding Dorsal and retaining it in the cytoplasm. |
| GO:0005515 protein binding | IPI PMID:10842059 Cactin, a conserved protein that interacts with the Drosophi... | REMOVE | Summary: Yeast two-hybrid identified cactin as a Cactus-interacting coiled-coil protein. Reason: Generic protein binding is uninformative. Cactin's molecular role is unclear (later work implicates it in splicing), so no more informative MF can be derived for Cactus from this interaction. Removal does not dispute the interaction. Supporting Evidence: PMID:10842059 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 |
| GO:0005515 protein binding | IPI PMID:20802461 Ξ²-arrestin Kurtz inhibits MAPK and Toll signalling in Drosop... | REMOVE | Summary: Cactus co-immunoprecipitates with the beta-arrestin Kurtz; Krz may stabilize Cactus. Reason: Generic protein binding is uninformative; the interaction suggests Krz regulates Cactus stability but does not define a Cactus molecular activity. Removal does not dispute the interaction. Supporting Evidence: PMID:20802461 We detected an interaction using co-immunoprecipitation from S2 cells ( Figure 7J ), as well as using in vitro translated proteins ( Supplementary Figure S7 ), suggesting a direct binding. |
| GO:0005515 protein binding | IPI PMID:9367441 An activity-dependent network of interactions links the Rel ... | MODIFY | Summary: Two-hybrid and co-immunoprecipitation show Cactus binds the Rel protein Dorsal. Reason: The partner is Dorsal, a Rel/NF-kappaB family transcription factor, and binding Dorsal is the core molecular activity of Cactus. Generic protein binding is uninformative; replace with NF-kappaB binding, which the paper supports. Proposed replacements: NF-kappaB binding Supporting Evidence: PMID:9367441 We show that Dorsal binds specifically to Tube, Pelle and Cactus PMID:7479760 Cactus, a Drosophila homologue of I kappa B, binds to and inhibits Dorsal |
| GO:0005737 cytoplasm | HDA PMID:26896675 A genome-wide resource for the analysis of protein localisat... | ACCEPT | Summary: Genome-wide GFP-tagged fosmid localisation screen detected Cact-GFP in muscle, in a pattern resembling neuromuscular junctions. Reason: Cytoplasmic localization of Cactus is well established; the HDA is consistent. Supporting Evidence: PMID:26896675 Cact-GFP (green) shows a distinct localisation in IFMs, leg and visceral muscle reminiscent of a neuromuscular junction pattern. PMID:7705656 Cactus, like its mammalian homolog I kappa B, inhibits nuclear translocation by binding Dorsal and retaining it in the cytoplasm. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location mapping to cytoplasm. Reason: Correct and consistent with experimental data; Cactus is a cytoplasmic protein that retains Dorsal/Dif in the cytoplasm. Supporting Evidence: PMID:7705656 Cactus, like its mammalian homolog I kappa B, inhibits nuclear translocation by binding Dorsal and retaining it in the cytoplasm. |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference from the IkappaB clade (IkBa family) that the protein is active in the cytosol. Reason: Cactus is inside the IkappaB clade, and experimental data show it is a soluble cytoplasmic protein that forms a cytoplasmic complex with Dorsal. Supporting Evidence: PMID:8227123 We show that dorsal and cactus are both phosphoproteins that form a stable cytoplasmic complex PMID:9025065 As in the case for I kappa B and NF-kappa B, Cactus inhibits Dorsal by retaining it in the cytoplasm. |
| GO:0005829 cytosol | IDA PMID:8227123 Dissociation of the dorsal-cactus complex and phosphorylatio... | ACCEPT | Summary: Cactus detected in the cytoplasm (embryo or fat body) by fractionation/immunostaining. Reason: Direct experimental evidence of cytoplasmic/cytosolic localization; this is where Cactus sequesters Dorsal/Dif. Supporting Evidence: PMID:8227123 We show that dorsal and cactus are both phosphoproteins that form a stable cytoplasmic complex |
| GO:0005829 cytosol | IDA PMID:9025065 A gradient of cytoplasmic Cactus degradation establishes the... | ACCEPT | Summary: Cactus detected in the cytoplasm (embryo or fat body) by fractionation/immunostaining. Reason: Direct experimental evidence of cytoplasmic/cytosolic localization; this is where Cactus sequesters Dorsal/Dif. Supporting Evidence: PMID:9025065 Cactus forms a cytoplasmic concentration gradient inversely correlated to the nuclear translocation gradient of Dorsal |
| GO:0005829 cytosol | IDA PMID:9553105 In vivo regulation of the IkappaB homologue cactus during th... | ACCEPT | Summary: Cactus detected in the cytoplasm (embryo or fat body) by fractionation/immunostaining. Reason: Direct experimental evidence of cytoplasmic/cytosolic localization; this is where Cactus sequesters Dorsal/Dif. Supporting Evidence: PMID:9553105 two Cactus isoforms are expressed in the cytoplasm of fat body cells and that they are rapidly degraded and resynthesized after immune challenge |
| GO:0005829 cytosol | TAS Reactome:R-DME-214845 | ACCEPT | Summary: Reactome places Cactus in the cytosol in the Drosophila Toll pathway reactions. Reason: Consistent with experimental evidence of cytoplasmic localization. Supporting Evidence: PMID:7705656 Cactus, like its mammalian homolog I kappa B, inhibits nuclear translocation by binding Dorsal and retaining it in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-DME-214847 | ACCEPT | Summary: Reactome places Cactus in the cytosol in the Drosophila Toll pathway reactions. Reason: Consistent with experimental evidence of cytoplasmic localization. Supporting Evidence: PMID:7705656 Cactus, like its mammalian homolog I kappa B, inhibits nuclear translocation by binding Dorsal and retaining it in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-DME-214857 | ACCEPT | Summary: Reactome places Cactus in the cytosol in the Drosophila Toll pathway reactions. Reason: Consistent with experimental evidence of cytoplasmic localization. Supporting Evidence: PMID:7705656 Cactus, like its mammalian homolog I kappa B, inhibits nuclear translocation by binding Dorsal and retaining it in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-DME-214860 | ACCEPT | Summary: Reactome places Cactus in the cytosol in the Drosophila Toll pathway reactions. Reason: Consistent with experimental evidence of cytoplasmic localization. Supporting Evidence: PMID:7705656 Cactus, like its mammalian homolog I kappa B, inhibits nuclear translocation by binding Dorsal and retaining it in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-DME-214864 | ACCEPT | Summary: Reactome places Cactus in the cytosol in the Drosophila Toll pathway reactions. Reason: Consistent with experimental evidence of cytoplasmic localization. Supporting Evidence: PMID:7705656 Cactus, like its mammalian homolog I kappa B, inhibits nuclear translocation by binding Dorsal and retaining it in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-DME-214871 | ACCEPT | Summary: Reactome places Cactus in the cytosol in the Drosophila Toll pathway reactions. Reason: Consistent with experimental evidence of cytoplasmic localization. Supporting Evidence: PMID:7705656 Cactus, like its mammalian homolog I kappa B, inhibits nuclear translocation by binding Dorsal and retaining it in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-DME-214880 | ACCEPT | Summary: Reactome places Cactus in the cytosol in the Drosophila Toll pathway reactions. Reason: Consistent with experimental evidence of cytoplasmic localization. Supporting Evidence: PMID:7705656 Cactus, like its mammalian homolog I kappa B, inhibits nuclear translocation by binding Dorsal and retaining it in the cytoplasm. |
| GO:0009950 dorsal/ventral axis specification | IMP PMID:10842059 Cactin, a conserved protein that interacts with the Drosophi... | ACCEPT | Summary: Enhancement of cactus loss-of-function ventralization by cactin overexpression; cactus alleles alter dorsoventral polarity. Reason: Cactus is a maternal component of the dorsoventral axis specification pathway: loss ventralizes, gain-of-function alleles dorsalize (PMID:1794309). Supporting Evidence: PMID:10842059 Over-expression of cactin in a cactus(A2) heterozygous background results in the enhancement of the cactus phenotype. PMID:1794309 loss of cactus function results in a ventralization of the body pattern |
| GO:0009953 dorsal/ventral pattern formation | IMP PMID:16782008 Weckle is a zinc finger adaptor of the toll pathway in dorso... | ACCEPT | Summary: cactus mutants alter embryonic dorsoventral pattern; Cactus degradation gradient shapes the nuclear Dorsal gradient. Reason: Well-established maternal role in embryonic dorsoventral patterning through regulation of Dorsal nuclear localization. Supporting Evidence: PMID:16782008 cactus is epistatic to wek, which in turn is epistatic to Toll |
| GO:0009953 dorsal/ventral pattern formation | IMP PMID:1794309 cactus, a maternal gene required for proper formation of the... | ACCEPT | Summary: cactus mutants alter embryonic dorsoventral pattern; Cactus degradation gradient shapes the nuclear Dorsal gradient. Reason: Well-established maternal role in embryonic dorsoventral patterning through regulation of Dorsal nuclear localization. Supporting Evidence: PMID:1794309 loss of cactus function results in a ventralization of the body pattern |
| GO:0009953 dorsal/ventral pattern formation | IMP PMID:7705656 Cactus protein degradation mediates Drosophila dorsal-ventra... | ACCEPT | Summary: cactus mutants alter embryonic dorsoventral pattern; Cactus degradation gradient shapes the nuclear Dorsal gradient. Reason: Well-established maternal role in embryonic dorsoventral patterning through regulation of Dorsal nuclear localization. Supporting Evidence: PMID:7705656 Cactus, like its mammalian homolog I kappa B, inhibits nuclear translocation by binding Dorsal and retaining it in the cytoplasm. |
| GO:0009953 dorsal/ventral pattern formation | IMP PMID:9025065 A gradient of cytoplasmic Cactus degradation establishes the... | ACCEPT | Summary: cactus mutants alter embryonic dorsoventral pattern; Cactus degradation gradient shapes the nuclear Dorsal gradient. Reason: Well-established maternal role in embryonic dorsoventral patterning through regulation of Dorsal nuclear localization. Supporting Evidence: PMID:9025065 Cactus forms a cytoplasmic concentration gradient inversely correlated to the nuclear translocation gradient of Dorsal |
| GO:0019730 antimicrobial humoral response | IEP PMID:9553105 In vivo regulation of the IkappaB homologue cactus during th... | KEEP AS NON CORE | Summary: cactus transcription is induced after immune challenge in the fat body (IEP). Reason: The expression evidence shows cactus is a Toll-induced feedback target. Cactus contributes to the humoral response as its negative regulator, which is captured more precisely by negative regulation of antifungal peptide production and negative regulation of Toll signaling pathway. The row is retained as non-core. Supporting Evidence: PMID:9553105 We observe that the cactus gene is up-regulated in response to immune challenge. |
| GO:0031594 neuromuscular junction | IDA PMID:10192771 Muscle structure and innervation are affected by loss of Dor... | KEEP AS NON CORE | Summary: Cactus (with Dorsal) accumulates postsynaptically at larval/adult glutamatergic neuromuscular junctions. Reason: Direct immunolocalization supports NMJ localization. This is a secondary, tissue-specific site; the core site of action is the cytoplasm/cytosol. Supporting Evidence: PMID:10192771 these proteins are distributed at low levels in the cytoplasm and nuclei and at much higher levels in the postsynaptic component of glutamatergic neuromuscular junctions |
| GO:0031594 neuromuscular junction | IDA PMID:12532402 Synaptic activity modifies the levels of Dorsal and Cactus a... | KEEP AS NON CORE | Summary: Cactus (with Dorsal) accumulates postsynaptically at larval/adult glutamatergic neuromuscular junctions. Reason: Direct immunolocalization supports NMJ localization. This is a secondary, tissue-specific site; the core site of action is the cytoplasm/cytosol. Supporting Evidence: PMID:12532402 the amount of these proteins at the neuromuscular junction is substantially decreased after electrical stimulation of the nerves or incubation in glutamate |
| GO:0043124 negative regulation of canonical NF-kappaB signal transduction | IBA GO_REF:0000033 | MODIFY | Summary: IBA from the IkappaB clade for negative regulation of canonical (IKK-dependent) NF-kappaB signaling. Reason: Cactus inherits the IkappaB inhibitory function, and the node placement is sound. However GO:0043124 regulates the canonical NF-kappaB cascade, which GO defines as IKK-dependent. In the fly Toll pathway Cactus is phosphorylated by Pelle and Drosophila IKK does not function in that pathway (PMID:24086459). The lineage-appropriate term, already carried by Cactus with abundant experimental support, is negative regulation of Toll signaling pathway. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: LINEAGE OR TAXON MISMATCH Sources checked: PANTHER:PTN008710654 SUPPORTS SOURCE BUT NOT TARGET IkappaB-clade ancestor; the inhibitory function is correctly inherited by Cactus, but the canonical NF-kappaB term is defined as IKK-dependent, and the fly Toll pathway uses Pelle rather than IKK as the Cactus kinase. The lineage-appropriate term is negative regulation of Toll signaling pathway. Proposed replacements: negative regulation of Toll signaling pathway Supporting Evidence: PMID:24086459 Surprisingly, the Drosophila IKK does not function in the fly Toll pathway PMID:24086459 We conclude that Pelle acts as a Cactus kinase and preferentially phosphorylates Cactus at the serines required for signal responsiveness. |
| GO:0043124 negative regulation of canonical NF-kappaB signal transduction | IMP PMID:7479760 Interactions of a Rel protein with its inhibitor. | MODIFY | Summary: Yeast reconstitution showing Cactus blocks Dorsal DNA binding and nuclear localization, annotated to negative regulation of canonical NF-kappaB signaling. Reason: The experiment establishes Cactus inhibition of the Rel protein Dorsal, which is correct. In flies this inhibition operates in the Toll pathway, which is IKK-independent (PMID:24086459), whereas GO:0043124 refers to the IKK-dependent canonical NF-kappaB cascade. Replace with negative regulation of Toll signaling pathway. Proposed replacements: negative regulation of Toll signaling pathway Supporting Evidence: PMID:7479760 Cactus blocks the DNA binding and nuclear localization functions of Dorsal PMID:24086459 Surprisingly, the Drosophila IKK does not function in the fly Toll pathway |
| GO:0045611 negative regulation of hemocyte differentiation | IMP PMID:27163255 The Friend of GATA Transcriptional Co-Regulator, U-Shaped, I... | KEEP AS NON CORE | Summary: RNAi knockdown of Cact in lymph gland prohemocytes promotes differentiation; Cactus maintains U-shaped levels to block differentiation. Reason: Supported by direct in vivo knockdown; a tissue-specific consequence of Cactus restraining Dorsal activity in hematopoietic progenitors. Supporting Evidence: PMID:27163255 over-expression of Dorsal, or knockdown of Cactus, promotes differentiation PMID:27163255 whereas Cactus maintained Ush levels to block differentiation |
| GO:0045751 negative regulation of Toll signaling pathway | IDA PMID:24086459 The IRAK homolog Pelle is the functional counterpart of IΞΊB ... | ACCEPT | Summary: Pelle phosphorylates Cactus at the signal-responsive serines, triggering its degradation and release of Rel proteins. Reason: Cactus is the IkappaB-type inhibitor of the Drosophila Toll pathway: it retains Dorsal and Dif in the cytoplasm until Toll-dependent, Pelle-mediated phosphorylation triggers its degradation. Negative regulation of Toll signaling pathway is the core process term for Cactus. Supporting Evidence: PMID:24086459 We conclude that Pelle acts as a Cactus kinase and preferentially phosphorylates Cactus at the serines required for signal responsiveness. PMID:24086459 Cactus, a fly IΞΊB protein, is the inhibitor for both Dif and Dorsal. |
| GO:0045751 negative regulation of Toll signaling pathway | IGI PMID:10843389 The Rel protein DIF mediates the antifungal but not the anti... | ACCEPT | Summary: Genetic epistasis with Dif places Cactus upstream of Dif in the Toll-dependent control of drosomycin. Reason: Cactus is the IkappaB-type inhibitor of the Drosophila Toll pathway: it retains Dorsal and Dif in the cytoplasm until Toll-dependent, Pelle-mediated phosphorylation triggers its degradation. Negative regulation of Toll signaling pathway is the core process term for Cactus. Supporting Evidence: PMID:10843389 Genetic epistasis experiments demonstrate that Dif mediates the Toll-dependent control of the inducibility of the antifungal peptide gene Drosomycin. |
| GO:0045751 negative regulation of Toll signaling pathway | IGI PMID:28621429 The SUMO-targeted ubiquitin ligase, Dgrn, is essential for D... | ACCEPT | Summary: Dgrn overexpression alleviates the inhibitory effect of Cactus on Toll/IMD output. Reason: Cactus is the IkappaB-type inhibitor of the Drosophila Toll pathway: it retains Dorsal and Dif in the cytoplasm until Toll-dependent, Pelle-mediated phosphorylation triggers its degradation. Negative regulation of Toll signaling pathway is the core process term for Cactus. Supporting Evidence: PMID:28621429 expression of Dgrn alleviated the inhibitory impact of the cytoplasmic |
| GO:0045751 negative regulation of Toll signaling pathway | IGI PMID:36516751 A Toll-dependent Bre1/Rad6-cact feedback loop in controlling... | ACCEPT | Summary: Bre1/Rad6-dependent induction of cactus forms a negative feedback loop on the Toll immune response. Reason: Cactus is the IkappaB-type inhibitor of the Drosophila Toll pathway: it retains Dorsal and Dif in the cytoplasm until Toll-dependent, Pelle-mediated phosphorylation triggers its degradation. Negative regulation of Toll signaling pathway is the core process term for Cactus. Supporting Evidence: PMID:36516751 cactus, the essential negative regulator of this pathway in flies |
| GO:0045751 negative regulation of Toll signaling pathway | IMP PMID:12431377 Sequential activation of signaling pathways during innate im... | ACCEPT | Summary: Genome-wide expression profiling of pathway mutants (including cactus) after microbial challenge. Reason: Cactus is the IkappaB-type inhibitor of the Drosophila Toll pathway: it retains Dorsal and Dif in the cytoplasm until Toll-dependent, Pelle-mediated phosphorylation triggers its degradation. Negative regulation of Toll signaling pathway is the core process term for Cactus. Supporting Evidence: PMID:12431377 We demonstrate that, in addition to signaling through the Toll and Imd pathways, signaling through the JNK and JAK/STAT pathways controls distinct subsets of targets induced by microbial agents. |
| GO:0045751 negative regulation of Toll signaling pathway | IMP PMID:1794309 cactus, a maternal gene required for proper formation of the... | ACCEPT | Summary: cactus loss increases nuclear uptake of Dorsal; cactus acts as negative regulator of the dorsal group pathway. Reason: Cactus is the IkappaB-type inhibitor of the Drosophila Toll pathway: it retains Dorsal and Dif in the cytoplasm until Toll-dependent, Pelle-mediated phosphorylation triggers its degradation. Negative regulation of Toll signaling pathway is the core process term for Cactus. Supporting Evidence: PMID:1794309 the maternal gene cactus acts as a negative regulator of the nuclear localization of the dorsal protein |
| GO:0045751 negative regulation of Toll signaling pathway | IMP PMID:7705656 Cactus protein degradation mediates Drosophila dorsal-ventra... | ACCEPT | Summary: Signal-dependent Cactus degradation is required for signaling; stable Cactus alleles block signaling. Reason: Cactus is the IkappaB-type inhibitor of the Drosophila Toll pathway: it retains Dorsal and Dif in the cytoplasm until Toll-dependent, Pelle-mediated phosphorylation triggers its degradation. Negative regulation of Toll signaling pathway is the core process term for Cactus. Supporting Evidence: PMID:7705656 Cactus, like its mammalian homolog I kappa B, inhibits nuclear translocation by binding Dorsal and retaining it in the cytoplasm. |
| GO:0045751 negative regulation of Toll signaling pathway | IMP PMID:9025065 A gradient of cytoplasmic Cactus degradation establishes the... | ACCEPT | Summary: A gradient of Cactus degradation establishes the Dorsal nuclear gradient. Reason: Cactus is the IkappaB-type inhibitor of the Drosophila Toll pathway: it retains Dorsal and Dif in the cytoplasm until Toll-dependent, Pelle-mediated phosphorylation triggers its degradation. Negative regulation of Toll signaling pathway is the core process term for Cactus. Supporting Evidence: PMID:9025065 Cactus forms a cytoplasmic concentration gradient inversely correlated to the nuclear translocation gradient of Dorsal |
| GO:0046843 dorsal appendage formation | HMP PMID:1783295 Female sterile mutations on the second chromosome of Drosoph... | UNDECIDED | Summary: High-throughput mutant phenotype from a large female-sterile screen of the second chromosome. Reason: The cached abstract of this screen paper does not mention cactus and the full text is not cached, so the specific cactus egg phenotype behind this HMP annotation cannot be verified. The best-characterized maternal role of cactus is in embryonic dorsoventral patterning rather than oogenesis per se; defer until the full text can be checked. Supporting Evidence: PMID:1783295 In 333 lines oogenesis proceeds apparently normally to stage 8 of oogenesis, but morphological defects become often apparent during later stages of oogenesis |
| GO:0048477 oogenesis | HMP PMID:1783295 Female sterile mutations on the second chromosome of Drosoph... | UNDECIDED | Summary: High-throughput mutant phenotype from a large female-sterile screen of the second chromosome. Reason: The cached abstract of this screen paper does not mention cactus and the full text is not cached, so the specific cactus egg phenotype behind this HMP annotation cannot be verified. The best-characterized maternal role of cactus is in embryonic dorsoventral patterning rather than oogenesis per se; defer until the full text can be checked. Supporting Evidence: PMID:1783295 In 333 lines oogenesis proceeds apparently normally to stage 8 of oogenesis, but morphological defects become often apparent during later stages of oogenesis |
| GO:0051059 NF-kappaB binding | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from the IkappaB clade: binding to NF-kappaB family transcription factors. Reason: Core IkappaB activity, experimentally confirmed for Cactus with Dorsal and Dif. Supporting Evidence: PMID:7479760 Cactus, a Drosophila homologue of I kappa B, binds to and inhibits Dorsal PMID:24086459 Cactus, a fly IΞΊB protein, is the inhibitor for both Dif and Dorsal. |
| GO:0051059 NF-kappaB binding | IPI PMID:7479760 Interactions of a Rel protein with its inhibitor. | ACCEPT | Summary: Cactus binds the Rel proteins Dorsal and Dif. Reason: Direct binding of Cactus to Rel/NF-kappaB family proteins is the basis of its inhibitory function; mutant Dorsal proteins that fail to bind Cactus escape inhibition. Supporting Evidence: PMID:7479760 Cactus, a Drosophila homologue of I kappa B, binds to and inhibits Dorsal PMID:24086459 Cactus, a fly IΞΊB protein, is the inhibitor for both Dif and Dorsal. |
| GO:0051059 NF-kappaB binding | IPI PMID:7479760 Interactions of a Rel protein with its inhibitor. | ACCEPT | Summary: Cactus binds the Rel proteins Dorsal and Dif. Reason: Direct binding of Cactus to Rel/NF-kappaB family proteins is the basis of its inhibitory function; mutant Dorsal proteins that fail to bind Cactus escape inhibition. Supporting Evidence: PMID:7479760 Cactus, a Drosophila homologue of I kappa B, binds to and inhibits Dorsal PMID:24086459 Cactus, a fly IΞΊB protein, is the inhibitor for both Dif and Dorsal. |
| GO:0071212 subsynaptic reticulum | IDA PMID:10192771 Muscle structure and innervation are affected by loss of Dor... | KEEP AS NON CORE | Summary: Cactus concentrated in the postsynaptic component of glutamatergic NMJs (subsynaptic reticulum). Reason: Immunolocalization supports postsynaptic accumulation at the NMJ; the curator mapped this to subsynaptic reticulum from the full text. Secondary, tissue-specific location. Supporting Evidence: PMID:10192771 these proteins are distributed at low levels in the cytoplasm and nuclei and at much higher levels in the postsynaptic component of glutamatergic neuromuscular junctions |
| GO:0140311 protein sequestering activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from the IkappaB clade: sequestering NF-kappaB proteins in the cytoplasm. Reason: Core function of Cactus: it binds Dorsal/Dif and retains them in the cytoplasm, preventing nuclear entry and DNA binding. Supporting Evidence: PMID:7705656 Cactus, like its mammalian homolog I kappa B, inhibits nuclear translocation by binding Dorsal and retaining it in the cytoplasm. PMID:9025065 As in the case for I kappa B and NF-kappa B, Cactus inhibits Dorsal by retaining it in the cytoplasm. |
| GO:0140311 protein sequestering activity | IMP PMID:7479760 Interactions of a Rel protein with its inhibitor. | ACCEPT | Summary: Cactus blocks Dorsal DNA binding and nuclear localization in a yeast reconstitution assay. Reason: Directly demonstrates the sequestering activity; Dorsal mutants that cannot bind Cactus escape inhibition. Supporting Evidence: PMID:7479760 Cactus blocks the DNA binding and nuclear localization functions of Dorsal PMID:7479760 Cactus, a Drosophila homologue of I kappa B, binds to and inhibits Dorsal |
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Download this section (compressed HTML)Q: Does Cactus sequester Dorsal and Dif with different affinities, and does this contribute to the different Rel-protein usage in embryo (Dorsal) versus adult fat body (Dif)?
Q: What is the in vivo role, if any, of IKKbeta (ird5/DLAK) in Cactus turnover, given that Pelle is the Toll-dependent Cactus kinase and IKK is dispensable for Toll signaling?
Q: Is the postsynaptic accumulation of Cactus and Dorsal at the NMJ controlled by Toll signaling or by a Toll-independent calcium/calcineurin pathway?
Q: Does GO need an explicit convention for IkappaB-family proteins acting in IKK-independent Rel pathways, so that IBA propagation of canonical NF-kappaB terms does not reach insect Cactus?
Experiment: Quantitative binding measurements (e.g. ITC or SPR) of full-length Cactus with Dorsal and Dif Rel-homology domains, including Cactus isoforms A and C.
Experiment: In vivo phospho-site mapping of Cactus in fat body after fungal infection in pelle kinase-dead versus ird5 mutant backgrounds to define which kinase acts in immunity.
Experiment: Muscle-specific cactus knockdown with electrophysiology to test whether postsynaptic Cactus regulates NMJ plasticity independently of Toll.
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Download this section (compressed HTML)cactus (cact) encodes the homolog of mammalian IkappaB. cact product acts as an inhibitor of NF-kappaB signaling by binding to the products of dl and Dif, which prevents their nuclear translocation. Toll signaling promotes the destruction of cact protein, which allows the products of dl and Dif to enter the nucleus and regulate gene expression.
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