Cul1

UniProt ID: Q24311
Organism: Drosophila melanogaster
Review Status: COMPLETE
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Gene Description

Cullin-1 (Cul1, lin-19) is the scaffold subunit of SCF (Skp1-Cul1-F-box) cullin-RING ubiquitin ligases in Drosophila. Its elongated N-terminal cullin-repeat domain binds the SkpA adaptor and thereby F-box substrate receptors (Slimb, Archipelago, Nutcracker, Fsn, Fbxo42, FipoQ and others), while its C-terminal cullin homology domain binds the RING protein Roc1a, which recruits the E2. Nedd8 conjugation to a conserved C-terminal lysine activates the ligase, and the COP9 signalosome removes it. SCF complexes built on Cul1 ubiquitinate phosphorylated substrates such as Cubitus interruptus, Armadillo, Cyclin E, Expanded and Akt, targeting them for proteasomal degradation or partial processing, and thereby act in Hedgehog, Wingless, Hippo, InR/TOR and IMD signaling, cell-cycle control, caspase activation during spermatid individualization, dendrite pruning and meiosis. In the auditory Johnston's organ, SCF activity built on Cul1, which the E3 ligase Ubr3 keeps in check, is needed for apical attachment of the scolopidia, and both RNAi knockdown and overexpression of Cul1 cause scolopidial detachment. Cul1 is found in the cytoplasm and nucleus.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0000209 protein polyubiquitination
IEA
GO_REF:0000117
ACCEPT
Summary: Protein polyubiquitination (ARBA).
Reason: Cul1 is the scaffold of SCF ligases that polyubiquitinate substrates (e.g. K11-linked chains on Ci); a direct process of the assembled ligase.
GO:0002785 negative regulation of antimicrobial peptide production
IMP
PMID:12401167
A ubiquitin-proteasome pathway represses the Drosophila immu...
KEEP AS NON CORE
Summary: Repression of IMD antimicrobial peptide expression.
Reason: Cul1 mutations induce Diptericin; output of SCF-dependent Relish control. Non-core.
Supporting Evidence:
PMID:12401167
mutations affecting either the Drosophila SCF components, Slimb and dCullin1, or the proteasome also induce Diptericin expression
GO:0005515 protein binding
IPI
PMID:17099689
Molecular dissection of the APC/C inhibitor Rca1 shows a nov...
MODIFY
Summary: Binding to SkpA.
Reason: Protein binding is uninformative; the Cul1-SkpA interaction is the scaffolding of the SCF, captured by GO:0160072 ubiquitin ligase complex scaffold activity.
GO:0005515 protein binding
IPI
PMID:17099689
Molecular dissection of the APC/C inhibitor Rca1 shows a nov...
MODIFY
Summary: Co-complex with the F-box protein Rca1.
Reason: Protein binding is uninformative; Cul1 associates with F-box proteins via SkpA as the SCF scaffold, captured by GO:0160072 ubiquitin ligase complex scaffold activity.
Supporting Evidence:
PMID:17099689
We propose that Rca1 acts as an F-box protein in an as yet uncharacterized SCF complex, which promotes S-phase entry.
GO:0005515 protein binding
IPI
PMID:19723762
Drosophila Minus is required for cell proliferation and infl...
REMOVE
Summary: Binding to Minus.
Reason: Minus associates with SCF(Ago) and Cyclin E; the bare protein binding term is uninformative and no specific Cul1 binding activity for Minus is established. Removed.
GO:0005634 nucleus
IBA
GO_REF:0000033
ACCEPT
Summary: Nucleus.
Reason: Cullins act in nuclear and cytoplasmic CRLs. IBA from PTN002631076 (donors include human CUL1-4 and multiple MODs).
GO:0005634 nucleus
IDA
PMID:12737805
The COP9 signalosome promotes degradation of Cyclin E during...
ACCEPT
Summary: Nucleus (IDA, CSN/Cyclin E oogenesis paper).
Reason: Abstract-only cache does not describe Cul1 subcellular localization; curators read the full text. Nuclear cullin activity is expected (Cyclin E degradation); accepted deferring to the curator.
GO:0005737 cytoplasm
EXP
PMID:20392747
A novel F-box protein is required for caspase activation dur...
ACCEPT
Summary: Cytoplasm.
Reason: Cul1-based SCF complexes act on cytoplasmic substrates (Ci-155, Arm). The EXP row is from the Nutcracker paper (full text cached but no explicit Cul1 localization statement found); accepted deferring to the curator.
GO:0005737 cytoplasm
IEA
GO_REF:0000044
ACCEPT
Summary: Cytoplasm.
Reason: Cul1-based SCF complexes act on cytoplasmic substrates (Ci-155, Arm). The EXP row is from the Nutcracker paper (full text cached but no explicit Cul1 localization statement found); accepted deferring to the curator.
GO:0005829 cytosol
IEA
GO_REF:0000117
ACCEPT
Summary: Cytosol.
Reason: Reactome places the fly SCF(Slimb) Arm and Ci ubiquitination reactions in the cytosol; consistent with cytoplasmic substrates. Acceptable.
GO:0005829 cytosol
TAS
Reactome:R-DME-209094
ACCEPT
Summary: Cytosol.
Reason: Reactome places the fly SCF(Slimb) Arm and Ci ubiquitination reactions in the cytosol; consistent with cytoplasmic substrates. Acceptable.
GO:0005829 cytosol
TAS
Reactome:R-DME-209102
ACCEPT
Summary: Cytosol.
Reason: Reactome places the fly SCF(Slimb) Arm and Ci ubiquitination reactions in the cytosol; consistent with cytoplasmic substrates. Acceptable.
GO:0005829 cytosol
TAS
Reactome:R-DME-209224
ACCEPT
Summary: Cytosol.
Reason: Reactome places the fly SCF(Slimb) Arm and Ci ubiquitination reactions in the cytosol; consistent with cytoplasmic substrates. Acceptable.
GO:0005829 cytosol
TAS
Reactome:R-DME-209278
ACCEPT
Summary: Cytosol.
Reason: Reactome places the fly SCF(Slimb) Arm and Ci ubiquitination reactions in the cytosol; consistent with cytoplasmic substrates. Acceptable.
GO:0006511 ubiquitin-dependent protein catabolic process
IEA
GO_REF:0000002
MODIFY
Summary: Ubiquitin-dependent protein catabolic process.
Reason: Correct but less specific than the evidence supports; Cul1 acts in SCF ligases whose substrates are degraded by the proteasome, so MODIFY to GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process (a term Cul1 already carries).
GO:0010564 regulation of cell cycle process
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: Regulation of cell cycle process (ARBA).
Reason: Broad but valid: SCF-Cul1 degrades Cyclin E and other cell-cycle regulators. Non-core.
GO:0016567 protein ubiquitination
IBA
GO_REF:0000033
MODIFY
Summary: Protein ubiquitination.
Reason: Correct but less specific than the evidence supports: Cul1 acts in a cullin-RING ligase that polyubiquitinates its substrates. Per the batch rule for correct-but-general terms, MODIFY to GO:0000209 protein polyubiquitination.
Proposed replacements: protein polyubiquitination
GO:0016567 protein ubiquitination
IC
PMID:18698375
Identifying determinants of cullin binding specificity among...
MODIFY
Summary: Protein ubiquitination.
Reason: Correct but less specific than the evidence supports: Cul1 acts in a cullin-RING ligase that polyubiquitinates its substrates. Per the batch rule for correct-but-general terms, MODIFY to GO:0000209 protein polyubiquitination.
Proposed replacements: protein polyubiquitination
Supporting Evidence:
PMID:18698375
we show that Drosophila Roc proteins bind specific Cullins: Roc1a binds Cul1-4
GO:0016567 protein ubiquitination
IC
PMID:24068890
A Cullin1-based SCF E3 ubiquitin ligase targets the InR/PI3K...
MODIFY
Summary: Protein ubiquitination.
Reason: Correct but less specific than the evidence supports: Cul1 acts in a cullin-RING ligase that polyubiquitinates its substrates. Per the batch rule for correct-but-general terms, MODIFY to GO:0000209 protein polyubiquitination.
Proposed replacements: protein polyubiquitination
Supporting Evidence:
PMID:24068890
the F-box protein Slimb forms a complex with Akt, an activator of the InR/PI3K/TOR pathway, and promotes Akt ubiquitination
GO:0016567 protein ubiquitination
IDA
PMID:26120032
Deubiquitination of Ci/Gli by Usp7/HAUSP Regulates Hedgehog ...
MODIFY
Summary: Protein ubiquitination.
Reason: Correct but less specific than the evidence supports: Cul1 acts in a cullin-RING ligase that polyubiquitinates its substrates. Per the batch rule for correct-but-general terms, MODIFY to GO:0000209 protein polyubiquitination.
Proposed replacements: protein polyubiquitination
Supporting Evidence:
PMID:26120032
which targets Ci ubiquitination mediated by Slimb-Cul1 E3 ligase
GO:0016567 protein ubiquitination
IDA
PMID:32467643
Dual functions of Rack1 in regulating Hedgehog pathway.
MODIFY
Summary: Protein ubiquitination.
Reason: Correct but less specific than the evidence supports: Cul1 acts in a cullin-RING ligase that polyubiquitinates its substrates. Per the batch rule for correct-but-general terms, MODIFY to GO:0000209 protein polyubiquitination.
Proposed replacements: protein polyubiquitination
Supporting Evidence:
PMID:32467643
the phosphorylated Ci protein is recognized and ubiquitinated by Slimb-Cul1 E3 ligase to partially degrade into a truncated form of Ci (Ci-75)
GO:0016567 protein ubiquitination
IEA
GO_REF:0000041
MODIFY
Summary: Protein ubiquitination.
Reason: Correct but less specific than the evidence supports: Cul1 acts in a cullin-RING ligase that polyubiquitinates its substrates. Per the batch rule for correct-but-general terms, MODIFY to GO:0000209 protein polyubiquitination.
Proposed replacements: protein polyubiquitination
GO:0019005 SCF ubiquitin ligase complex
IBA
GO_REF:0000033
ACCEPT
Summary: Cul1 is the cullin scaffold of SCF complexes.
Reason: Well supported by fly co-IP and genetic data with SkpA, Roc1a and multiple F-box proteins.
GO:0019005 SCF ubiquitin ligase complex
IDA
PMID:11500045
Occurrence of a putative SCF ubiquitin ligase complex in Dro...
ACCEPT
Summary: Cul1 is the cullin scaffold of SCF complexes.
Reason: Well supported by fly co-IP and genetic data with SkpA, Roc1a and multiple F-box proteins.
Supporting Evidence:
PMID:11500045
We show that putative Drosophila SCF core subunits dSkpA and dRbx1 both interact directly with dCu11 and the F-box protein Slmb.
GO:0019005 SCF ubiquitin ligase complex
IDA
PMID:17925225
Regulation of Ci-SCFSlimb binding, Ci proteolysis, and hedge...
ACCEPT
Summary: Cul1 is the cullin scaffold of SCF complexes.
Reason: Well supported by fly co-IP and genetic data with SkpA, Roc1a and multiple F-box proteins.
Supporting Evidence:
PMID:17925225
When Hh is absent, phosphorylation of Ci/Gli triggers binding to SCF ubiquitin ligase complexes and consequent proteolysis.
GO:0019005 SCF ubiquitin ligase complex
IDA
PMID:18698375
Identifying determinants of cullin binding specificity among...
ACCEPT
Summary: Cul1 is the cullin scaffold of SCF complexes.
Reason: Well supported by fly co-IP and genetic data with SkpA, Roc1a and multiple F-box proteins.
Supporting Evidence:
PMID:18698375
we show that Drosophila Roc proteins bind specific Cullins: Roc1a binds Cul1-4
GO:0019005 SCF ubiquitin ligase complex
IDA
PMID:20123973
Regulation of Drosophila vasa in vivo through paralogous cul...
ACCEPT
Summary: SCF complex (Fsn/Gus Vasa paper).
Reason: Abstract-only cache names Fsn as a Cullin-RING specificity receptor but does not mention Cul1; curators read the full text. Accepted deferring to the curator.
GO:0019005 SCF ubiquitin ligase complex
IDA
PMID:23747190
Ter94 ATPase complex targets k11-linked ubiquitinated ci to ...
ACCEPT
Summary: Cul1 is the cullin scaffold of SCF complexes.
Reason: Well supported by fly co-IP and genetic data with SkpA, Roc1a and multiple F-box proteins.
Supporting Evidence:
PMID:23747190
Ter94(Ufd1-like/dNpl4) complex interacts directly with Cul1-Slimb
GO:0019005 SCF ubiquitin ligase complex
IDA
PMID:24068890
A Cullin1-based SCF E3 ubiquitin ligase targets the InR/PI3K...
ACCEPT
Summary: Cul1 is the cullin scaffold of SCF complexes.
Reason: Well supported by fly co-IP and genetic data with SkpA, Roc1a and multiple F-box proteins.
Supporting Evidence:
PMID:24068890
The SCF E3 ligase consists of four core components Cullin1/Roc1a/SkpA/Slimb
GO:0019005 SCF ubiquitin ligase complex
IDA
PMID:33382409
SCF-Fbxo42 promotes synaptonemal complex assembly by downreg...
ACCEPT
Summary: Cul1 is the cullin scaffold of SCF complexes.
Reason: Well supported by fly co-IP and genetic data with SkpA, Roc1a and multiple F-box proteins.
Supporting Evidence:
PMID:33382409
It consists of three core subunits (Roc, Cul1, and Skp1) and one variable subunit (an F-box protein
GO:0019005 SCF ubiquitin ligase complex
IEA
GO_REF:0000117
ACCEPT
Summary: Cul1 is the cullin scaffold of SCF complexes.
Reason: Well supported by fly co-IP and genetic data with SkpA, Roc1a and multiple F-box proteins.
GO:0019005 SCF ubiquitin ligase complex
IMP
PMID:22359584
Defining components of the ß-catenin destruction complex and...
ACCEPT
Summary: Cul1 is the cullin scaffold of SCF complexes.
Reason: Well supported by fly co-IP and genetic data with SkpA, Roc1a and multiple F-box proteins.
Supporting Evidence:
PMID:22359584
Using RNAi in Drosophila S2 cells to examine which SCF components are essential for Armadillo destruction
GO:0019005 SCF ubiquitin ligase complex
IPI
PMID:11500045
Occurrence of a putative SCF ubiquitin ligase complex in Dro...
ACCEPT
Summary: Cul1 is the cullin scaffold of SCF complexes.
Reason: Well supported by fly co-IP and genetic data with SkpA, Roc1a and multiple F-box proteins.
Supporting Evidence:
PMID:11500045
We show that putative Drosophila SCF core subunits dSkpA and dRbx1 both interact directly with dCu11 and the F-box protein Slmb.
GO:0030163 protein catabolic process
IEA
GO_REF:0000117
MODIFY
Summary: Protein catabolic process.
Reason: Correct but less specific than the evidence supports; Cul1 acts in SCF ligases whose substrates are degraded by the proteasome, so MODIFY to GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process (a term Cul1 already carries).
GO:0030163 protein catabolic process
IMP
PMID:24068890
A Cullin1-based SCF E3 ubiquitin ligase targets the InR/PI3K...
MODIFY
Summary: Protein catabolic process.
Reason: Correct but less specific than the evidence supports; Cul1 acts in SCF ligases whose substrates are degraded by the proteasome, so MODIFY to GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process (a term Cul1 already carries).
Supporting Evidence:
PMID:24068890
the Cullin1-based E3 ligase facilitates ddaC dendrite pruning primarily through inactivation of the InR/PI3K/TOR pathway
GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
IBA
GO_REF:0000033
ACCEPT
Summary: SCF-dependent proteasomal protein catabolism.
Reason: Core process of the Cul1-based SCF ligases.
GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
NAS
PMID:11500045
Occurrence of a putative SCF ubiquitin ligase complex in Dro...
ACCEPT
Summary: SCF-dependent proteasomal protein catabolism.
Reason: Core process of the Cul1-based SCF ligases.
Supporting Evidence:
PMID:11500045
Our results suggest that dRbx1, dSkpA, dCullin1, and Slimb proteins are components of a Drosophila SCF complex that functions in combination with the ubiquitin conjugating enzyme UbcD1.
GO:0031398 positive regulation of protein ubiquitination
IMP
PMID:30685895
FipoQ/FBXO33, a Cullin-1-based ubiquitin ligase complex comp...
KEEP AS NON CORE
Summary: Positive regulation of protein ubiquitination (SCA3 polyQ).
Reason: Cul1 knockdown alters ubiquitination and solubility of expanded SCA3; Cul1 is a structural part of the ligase rather than a regulator, so this is an indirect framing of its core activity. Non-core.
Supporting Evidence:
PMID:30685895
the knockdown of Cul1 expression enhances SCA3-induced neurodegeneration and reduces the solubility of expanded SCA3-polyQ proteins
GO:0031461 cullin-RING ubiquitin ligase complex
IEA
GO_REF:0000002
MODIFY
Summary: Cullin-RING ubiquitin ligase complex (InterPro).
Reason: Correct but less specific than the evidence supports: Cul1 is specifically the cullin of SCF complexes, so MODIFY to GO:0019005 SCF ubiquitin ligase complex, which Cul1 already carries.
Proposed replacements: SCF ubiquitin ligase complex
GO:0031625 ubiquitin protein ligase binding
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: Ubiquitin protein ligase binding.
Reason: Cul1 binds the RING E3 subunit Roc1a; accurate structural binding descriptor but subsumed by its scaffold activity (GO:0160072). Non-core.
GO:0031625 ubiquitin protein ligase binding
IEA
GO_REF:0000002
KEEP AS NON CORE
Summary: Ubiquitin protein ligase binding.
Reason: Cul1 binds the RING E3 subunit Roc1a; accurate structural binding descriptor but subsumed by its scaffold activity (GO:0160072). Non-core.
GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process
IMP
PMID:22359584
Defining components of the ß-catenin destruction complex and...
KEEP AS NON CORE
Summary: Positive regulation of proteasomal ubiquitin-dependent catabolism.
Reason: The cullin-RING ligase containing Cul1 executes rather than regulates substrate degradation; the direct process is GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process. The regulation term is a common E3-ligase convention and is kept as non-core.
Supporting Evidence:
PMID:22359584
Using RNAi in Drosophila S2 cells to examine which SCF components are essential for Armadillo destruction
GO:0035331 negative regulation of hippo signaling
IMP
PMID:25522691
SCF(Slmb) E3 ligase-mediated degradation of Expanded is inhi...
KEEP AS NON CORE
Summary: Negative regulation of Hippo signaling.
Reason: Cul1 as SCF(Slimb) scaffold is needed for Expanded/Kibra degradation; non-core output of the shared core.
Supporting Evidence:
PMID:25522691
the SCF(Slmb) E3 ligase as a novel negative regulator of the Hippo pathway in Drosophila imaginal tissues
GO:0035331 negative regulation of hippo signaling
IMP
PMID:33555257
Negative feedback couples Hippo pathway activation with Kibr...
KEEP AS NON CORE
Summary: Negative regulation of Hippo signaling.
Reason: Cul1 as SCF(Slimb) scaffold is needed for Expanded/Kibra degradation; non-core output of the shared core.
Supporting Evidence:
PMID:33555257
Hpo signaling complex formation promotes Kib degradation via SCFSlimb-mediated ubiquitination
GO:0043066 negative regulation of apoptotic process
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: Negative regulation of apoptosis.
Reason: Reported for SCF/dRYBP-dependent maintenance of DIAP1; non-core physiological output.
GO:0043066 negative regulation of apoptotic process
IMP
PMID:23979704
A novel dRYBP-SCF complex functions to inhibit apoptosis in ...
KEEP AS NON CORE
Summary: Negative regulation of apoptosis.
Reason: Reported for SCF/dRYBP-dependent maintenance of DIAP1; non-core physiological output.
Supporting Evidence:
PMID:23979704
interacts both genetically and biochemically with the E3 ubiquitin ligase SKPA, dCULLIN, F-box (SCF) complex to synergistically inhibit apoptosis in Drosophila
GO:0045879 negative regulation of smoothened signaling pathway
IDA
PMID:32467643
Dual functions of Rack1 in regulating Hedgehog pathway.
KEEP AS NON CORE
Summary: Negative regulation of Hedgehog signaling.
Reason: Cul1-based SCF(Slimb) processes Ci; for the shared cullin scaffold this pathway output is non-core (it is accepted as a defining role for Slimb).
Supporting Evidence:
PMID:32467643
the phosphorylated Ci protein is recognized and ubiquitinated by Slimb-Cul1 E3 ligase to partially degrade into a truncated form of Ci (Ci-75)
GO:0045879 negative regulation of smoothened signaling pathway
IMP
PMID:12231629
Distinct protein degradation mechanisms mediated by Cul1 and...
KEEP AS NON CORE
Summary: Negative regulation of Hedgehog signaling.
Reason: Cul1-based SCF(Slimb) processes Ci; for the shared cullin scaffold this pathway output is non-core (it is accepted as a defining role for Slimb).
Supporting Evidence:
PMID:12231629
In cells anterior to the MF, Ci proteolytic processing promoted by PKA requires the activity of the Nedd8-modified Cul1-based SCF(Slimb) complex.
GO:0045879 negative regulation of smoothened signaling pathway
IMP
PMID:26120032
Deubiquitination of Ci/Gli by Usp7/HAUSP Regulates Hedgehog ...
KEEP AS NON CORE
Summary: Negative regulation of Hedgehog signaling.
Reason: Cul1-based SCF(Slimb) processes Ci; for the shared cullin scaffold this pathway output is non-core (it is accepted as a defining role for Slimb).
Supporting Evidence:
PMID:26120032
inhibiting Ci ubiquitination and degradation mediated by both Slimb-Cul1 and Hib-Cul3 E3 ligases
GO:0046627 negative regulation of insulin receptor signaling pathway
IGI
PMID:24068890
A Cullin1-based SCF E3 ubiquitin ligase targets the InR/PI3K...
KEEP AS NON CORE
Summary: Negative regulation of insulin receptor signaling.
Reason: SCF-Cul1 inactivates InR/PI3K/TOR during dendrite pruning; context-specific output.
Supporting Evidence:
PMID:24068890
the Cullin1-based E3 ligase facilitates ddaC dendrite pruning primarily through inactivation of the InR/PI3K/TOR pathway
GO:0051898 negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
IGI
PMID:24068890
A Cullin1-based SCF E3 ubiquitin ligase targets the InR/PI3K...
KEEP AS NON CORE
Summary: Negative regulation of PI3K/Akt signaling.
Reason: SCF-Cul1 promotes Akt ubiquitination via Slimb during pruning; context-specific.
Supporting Evidence:
PMID:24068890
the F-box protein Slimb forms a complex with Akt, an activator of the InR/PI3K/TOR pathway, and promotes Akt ubiquitination
GO:0061060 negative regulation of peptidoglycan recognition protein signaling pathway
IMP
PMID:12401167
A ubiquitin-proteasome pathway represses the Drosophila immu...
KEEP AS NON CORE
Summary: Negative regulation of PGRP (IMD) signaling.
Reason: Cul1 mutations derepress Diptericin; non-core.
Supporting Evidence:
PMID:12401167
mutations affecting either the Drosophila SCF components, Slimb and dCullin1, or the proteasome also induce Diptericin expression
GO:0070979 protein K11-linked ubiquitination
IDA
PMID:23747190
Ter94 ATPase complex targets k11-linked ubiquitinated ci to ...
ACCEPT
Summary: K11-linked ubiquitination of Ci.
Reason: Cul1-Slimb E3 adds K11-linked chains to Ci; direct activity of the assembled ligase.
Supporting Evidence:
PMID:23747190
We demonstrate that Cul1-Slimb-based E3 ligase, but not Cul3-Rdx-based E3 ligase, modifies Ci by efficient addition of K11-linked ubiquitin chains.
GO:0090090 negative regulation of canonical Wnt signaling pathway
IMP
PMID:21628596
Drosophila homeodomain-interacting protein kinase inhibits t...
KEEP AS NON CORE
Summary: Negative regulation of canonical Wnt signaling.
Reason: Cul1-based SCF(Slimb) destroys Armadillo; non-core output for the shared scaffold.
Supporting Evidence:
PMID:21628596
Hipk acts to stabilize Armadillo by impeding the function of the E3 ubiquitin ligase Skp1-Cul1-F-box (SCF)(Slimb), thereby inhibiting Armadillo ubiquitination and subsequent degradation.
GO:0090090 negative regulation of canonical Wnt signaling pathway
IMP
PMID:22359584
Defining components of the ß-catenin destruction complex and...
KEEP AS NON CORE
Summary: Negative regulation of canonical Wnt signaling.
Reason: Cul1-based SCF(Slimb) destroys Armadillo; non-core output for the shared scaffold.
Supporting Evidence:
PMID:22359584
Using RNAi in Drosophila S2 cells to examine which SCF components are essential for Armadillo destruction
GO:0160072 ubiquitin ligase complex scaffold activity
IBA
GO_REF:0000033
ACCEPT
Summary: Ubiquitin ligase complex scaffold activity.
Reason: Defining molecular function of cullins: Cul1 binds SkpA/F-box and Roc1a modules and positions substrate and E2.
GO:0160072 ubiquitin ligase complex scaffold activity
IPI
PMID:11500045
Occurrence of a putative SCF ubiquitin ligase complex in Dro...
ACCEPT
Summary: Ubiquitin ligase complex scaffold activity.
Reason: Defining molecular function of cullins: Cul1 binds SkpA/F-box and Roc1a modules and positions substrate and E2.
Supporting Evidence:
PMID:11500045
We show that putative Drosophila SCF core subunits dSkpA and dRbx1 both interact directly with dCu11 and the F-box protein Slmb.
GO:0160072 ubiquitin ligase complex scaffold activity
IPI
PMID:17925225
Regulation of Ci-SCFSlimb binding, Ci proteolysis, and hedge...
ACCEPT
Summary: Ubiquitin ligase complex scaffold activity.
Reason: Defining molecular function of cullins: Cul1 binds SkpA/F-box and Roc1a modules and positions substrate and E2.
Supporting Evidence:
PMID:17925225
When Hh is absent, phosphorylation of Ci/Gli triggers binding to SCF ubiquitin ligase complexes and consequent proteolysis.
GO:0160072 ubiquitin ligase complex scaffold activity
IPI
PMID:18698375
Identifying determinants of cullin binding specificity among...
ACCEPT
Summary: Ubiquitin ligase complex scaffold activity.
Reason: Defining molecular function of cullins: Cul1 binds SkpA/F-box and Roc1a modules and positions substrate and E2.
Supporting Evidence:
PMID:18698375
Cullin binding specificity is strongly influenced by the Roc NH(2)-terminal domain, which forms an inter-molecular beta sheet with the Cullin
GO:1902532 negative regulation of intracellular signal transduction
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: Negative regulation of intracellular signal transduction (ARBA).
Reason: Very broad grouping of the Hh, Wnt and InR pathway outputs; valid but uninformative. Non-core.
GO:1904801 positive regulation of neuron remodeling
IMP
PMID:24068890
A Cullin1-based SCF E3 ubiquitin ligase targets the InR/PI3K...
KEEP AS NON CORE
Summary: Positive regulation of neuron remodeling.
Reason: Cul1 is required for ddaC dendrite and MB axon pruning; developmental output.
Supporting Evidence:
PMID:24068890
Here, we identified a conserved SCF E3 ubiquitin ligase that plays a critical role in pruning of both ddaC dendrites and mushroom body Ξ³ axons.
GO:1905088 positive regulation of synaptonemal complex assembly
IMP
PMID:33382409
SCF-Fbxo42 promotes synaptonemal complex assembly by downreg...
KEEP AS NON CORE
Summary: Positive regulation of synaptonemal complex assembly.
Reason: SCF core is needed for synaptonemal complex assembly in female meiosis; non-core.
Supporting Evidence:
PMID:33382409
We found that the ubiquitin ligase complex SCF is important for assembly and maintenance of the synaptonemal complex in Drosophila female meiosis.

Core Functions

Cul1 is the rigid cullin scaffold of SCF ligases: its N-terminal repeats bind SkpA (and through it F-box substrate receptors) and its C-terminal cullin homology domain binds Roc1a, positioning substrate and Roc1a-bound E2 for ubiquitin transfer; Nedd8 modification activates it.

Supporting Evidence:
  • PMID:11500045
    We show that putative Drosophila SCF core subunits dSkpA and dRbx1 both interact directly with dCu11 and the F-box protein Slmb.
  • PMID:12231629
    suggesting that the Cul1-based SCF complex requires Nedd8 modification for the degradation processes of Ci, Arm, and CycE in vivo

References

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Suggested Questions for Experts

Q: How is Cul1 neddylation/deneddylation (CSN) cycling coordinated with F-box exchange (Cand1) to switch between SCF(Slimb), SCF(Ago) and testis SCF(Nutcracker) in vivo?

Suggested Experiments

Experiment: Rescue Cul1 null clones with wild-type or Nedd8-site mutant Cul1 and measure Ci-75/Ci-155 ratios, Arm and Cyclin E levels in wing and eye discs.

Hypothesis: Neddylation-defective Cul1 (K->R at the conserved Nedd8 site) cannot support Ci processing or Cyclin E degradation in vivo.

Deep Research

Falcon

(Cul1-deep-research-falcon.md)

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πŸ“š Additional Documentation

Notes

(Cul1-notes.md)

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