CAND1 (Cullin-Associated and Neddylation-Dissociated 1; originally TIP120A) is a large HEAT-repeat protein that regulates the assembly and dynamic remodeling of cullin-RING E3 ubiquitin ligases (CRLs), most prominently SCF (SKP1-CUL1-F-box) complexes. CAND1 binds the unneddylated CUL1-RBX1 (ROC1) catalytic core and clamps around the cullin scaffold, with a beta-hairpin occupying the SKP1-adaptor binding site so that SKP1/F-box subunits cannot bind simultaneously. Rather than acting as a static inhibitor, CAND1 functions as a substrate-receptor (F-box protein) exchange factor: it accelerates dissociation of existing SCF complexes and promotes exchange of F-box receptors, allowing a common cullin-RBX1 core to be redistributed among many different substrate receptors. Its action is reciprocally coupled to the neddylation cycle - CUL1 neddylation (and binding of SKP1/F-box plus substrate) dissociates CAND1, while deneddylation regenerates the CAND1-bound state. Through this exchange activity CAND1 is a positive regulator of overall CRL activity in vivo and acts on cullins broadly, not just CUL1. CAND1 is predominantly cytoplasmic with nuclear pools, and it is a regulator/assembly factor rather than a catalytic ubiquitin-transfer enzyme.
Definition: A molecular function in which a protein binds an unneddylated cullin-RING ligase (CRL) core and catalyzes the dissociation and exchange of substrate-receptor (e.g. F-box) modules, thereby remodeling the repertoire of assembled CRL complexes. Distinct from a simple adaptor/binding activity in that it actively accelerates receptor cycling.
Justification: CAND1's defining, conserved mechanistic role is acting as a substrate-receptor exchange factor for cullin-RING ligases (clamping the unneddylated CUL1-RBX1 core and accelerating F-box receptor exchange). No existing GO molecular function term captures this exchange-factor activity; the closest existing terms (molecular adaptor activity, SCF complex assembly) understate the active, catalytic exchange mechanism. This gap is why no molecular_function is asserted in core_functions.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: CAND1 has nuclear pools (e.g., acting on nuclear CRL4) in addition to its predominant cytoplasmic localization; nuclear activity is supported. Reason: CAND1 regulates nuclear CRLs and is detected in the nucleus; nuclear localization is well supported, though CAND1 is predominantly cytoplasmic. Supporting Evidence: PMID:21249194 CAND1 is predominantly cytoplasmically localized |
| GO:0010265 SCF complex assembly | IBA GO_REF:0000033 | ACCEPT | Summary: Regulation of SCF complex assembly via F-box exchange is the core biological process for CAND1 and is strongly supported experimentally. Reason: CAND1 binds unneddylated CUL1-RBX1 and regulates SCF assembly/disassembly, promoting F-box receptor exchange; this is its defining role. Supporting Evidence: PMID:12504026 CAND1 regulates the formation of the SCF complex PMID:15537541 forms a tight complex with the Cul1-Roc1 |
| GO:0016567 protein ubiquitination | IBA GO_REF:0000033 | ACCEPT | Summary: CAND1 is involved in (regulates) CRL-mediated protein ubiquitination as an assembly/exchange factor, not as a catalytic enzyme; involved_in is appropriate. Reason: By controlling SCF/CRL assembly and F-box exchange, CAND1 modulates ubiquitination of CRL substrates; the regulatory involvement is well supported. Supporting Evidence: PMID:12609982 TIP120A greatly reduced the ubiquitination of phosphorylated |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: Nuclear localization consistent with CAND1 regulating nuclear CRLs. Reason: Nuclear pools of CAND1 are supported; localization annotation is appropriate. Supporting Evidence: PMID:21249194 CAND1 is predominantly cytoplasmically localized |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: CAND1 is predominantly cytoplasmic, where most cullins reside; this is a core localization. Reason: Directly supported - CAND1 is predominantly cytoplasmically localized with cullins as major interactors. Supporting Evidence: PMID:21249194 CAND1 is predominantly cytoplasmically localized |
| GO:0010265 SCF complex assembly | IEA GO_REF:0000002 | ACCEPT | Summary: Same core process as the IBA annotation; CAND1 regulates SCF assembly via F-box exchange. Reason: Strongly supported core function consistent with InterPro/experimental evidence. Supporting Evidence: PMID:12504026 CAND1 regulates the formation of the SCF complex |
| GO:0005515 protein binding | IPI PMID:12504026 CAND1 binds to unneddylated CUL1 and regulates the formation... | MARK AS OVER ANNOTATED | Summary: The underlying interaction is CAND1 binding unneddylated CUL1, which is captured by the specific CRL-complex and SCF-assembly terms; bare protein binding is uninformative. Reason: protein binding is too generic; CAND1-CUL1 binding is represented by more informative terms in this review. |
| GO:0005515 protein binding | IPI PMID:12609982 TIP120A associates with cullins and modulates ubiquitin liga... | MARK AS OVER ANNOTATED | Summary: The underlying interaction is CAND1 (TIP120A) with cullins/Rbx1; captured by specific CRL terms. Bare protein binding is uninformative. Reason: protein binding is too generic; the cullin interactions are represented by specific terms. |
| GO:0005515 protein binding | IPI PMID:15537541 Structure of the Cand1-Cul1-Roc1 complex reveals regulatory ... | MARK AS OVER ANNOTATED | Summary: The interaction is CAND1-CUL1-ROC1 (structural); captured by specific CRL/SCF terms. Bare protein binding is uninformative. Reason: protein binding is too generic; the structural CAND1-CUL1-ROC1 interaction is represented by specific terms. |
| GO:0005515 protein binding | IPI PMID:16861300 Regulation of neddylation and deneddylation of cullin1 in SC... | MARK AS OVER ANNOTATED | Summary: The interaction concerns the cullin-CAND1 complex and its dissociation; captured by specific CRL terms. Bare protein binding is uninformative. Reason: protein binding is too generic for this CRL-regulatory interaction. |
| GO:0005515 protein binding | IPI PMID:17290223 Impaired DNA damage checkpoint response in MIF-deficient mic... | MARK AS OVER ANNOTATED | Summary: Generic protein-binding annotation; uninformative for CAND1 function. Reason: Bare protein binding from a non-mechanistic interaction record is not informative. |
| GO:0005515 protein binding | IPI PMID:21145461 Dynamics of cullin-RING ubiquitin ligase network revealed by... | MARK AS OVER ANNOTATED | Summary: From systematic CRL-network proteomics; the relevant CAND1 biology is captured by CRL-complex/SCF-assembly terms, so bare protein binding is uninformative. Reason: protein binding is too generic; CRL-network membership is better represented by specific terms. |
| GO:0005515 protein binding | IPI PMID:25435324 Structural mechanism of nuclear transport mediated by import... | MARK AS OVER ANNOTATED | Summary: Generic protein-binding annotation from an importin-beta transport-mechanism study; uninformative for CAND1 function. Reason: Bare protein binding is not informative. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MARK AS OVER ANNOTATED | Summary: Generic protein-binding annotation from a quantitative interactome study; uninformative for CAND1 function. Reason: Bare protein binding from a high-throughput interactome is not informative. |
| GO:0005515 protein binding | IPI PMID:30021884 Histone Interaction Landscapes Visualized by Crosslinking Ma... | MARK AS OVER ANNOTATED | Summary: Generic protein-binding annotation from a histone crosslinking-MS study; uninformative for CAND1 function. Reason: Bare protein binding from a high-throughput interactome is not informative. |
| GO:0005515 protein binding | IPI PMID:34591642 A protein network map of head and neck cancer reveals PIK3CA... | MARK AS OVER ANNOTATED | Summary: Generic protein-binding annotation from a head-and-neck-cancer network map; uninformative for CAND1 function. Reason: Bare protein binding from a high-throughput interactome is not informative. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MARK AS OVER ANNOTATED | Summary: Generic protein-binding annotation from a multimodal cell-map study; uninformative for CAND1 function. Reason: Bare protein binding from a high-throughput interactome is not informative. |
| GO:0017025 TBP-class protein binding | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: This derives from the historical TIP120A characterization as a TBP-interacting transcriptional regulator and predates the CRL-assembly paradigm; it is not the consensus core function of CAND1. Reason: TBP binding reflects early TIP120A literature; the established CAND1 function is CRL/SCF assembly regulation, and TBP-class binding is not part of that core. Supporting Evidence: PMID:10581176 TBP-interacting protein 120A (TIP120A) is a novel eukaryotic transcriptional |
| GO:0045893 positive regulation of DNA-templated transcription | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Transcriptional activation derives from the historical TIP120A work and is not the established core CAND1 function (CRL assembly regulation). Reason: This is a historical/secondary TIP120A-era function and an indirect/broad effect, not the consensus CAND1 role. Supporting Evidence: PMID:10581176 differentiation-related gene expression |
| GO:0045899 positive regulation of RNA polymerase II transcription preinitiation complex assembly | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Derives from historical TIP120A transcription work; not the established core CAND1 function. Reason: Historical/secondary TIP120A-era function, not the consensus CRL-assembly role. Supporting Evidence: PMID:10581176 TBP-interacting protein 120A (TIP120A) is a novel eukaryotic transcriptional |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Nucleoplasmic localization is consistent with CAND1 nuclear pools acting on nuclear CRLs. Reason: Supported by immunofluorescence localization and consistent with CAND1's nuclear CRL-regulatory role. Supporting Evidence: PMID:21249194 CAND1 is predominantly cytoplasmically localized |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Cytosolic localization is the predominant CAND1 localization and a core functional compartment. Reason: Directly supported - CAND1 is predominantly cytoplasmic with cullins as major interactors. Supporting Evidence: PMID:21249194 CAND1 is predominantly cytoplasmically localized |
| GO:0005515 protein binding | IPI PMID:27542266 DCUN1D3 activates SCFSKP2 ubiquitin E3 ligase activity and c... | MARK AS OVER ANNOTATED | Summary: Generic protein-binding annotation from a DCUN1D3/SCF-SKP2 study; uninformative for CAND1 function. Reason: Bare protein binding is not informative. |
| GO:0005515 protein binding | IPI PMID:26906416 Characterization of the mammalian family of DCN-type NEDD8 E... | MARK AS OVER ANNOTATED | Summary: Generic protein-binding annotation from a DCN-type NEDD8 E3 ligase study; uninformative for CAND1 function. Reason: Bare protein binding is not informative. |
| GO:0005515 protein binding | IPI PMID:24192928 Oncogenic function of SCCRO5/DCUN1D5 requires its Neddylatio... | MARK AS OVER ANNOTATED | Summary: Generic protein-binding annotation from a SCCRO5/DCUN1D5 study; uninformative for CAND1 function. Reason: Bare protein binding is not informative. |
| GO:0005515 protein binding | IPI PMID:26030138 Identification of Novel Proteins Co-Purifying with Cockayne ... | MARK AS OVER ANNOTATED | Summary: Generic protein-binding annotation from a CSB co-purification study; uninformative for CAND1 function. Reason: Bare protein binding is not informative. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8955245 | ACCEPT | Summary: Nucleoplasmic localization (CAND1 binds nuclear CRL4) is consistent with CAND1 nuclear function. Reason: Supported by CAND1 regulation of nuclear CRLs (CRL4) per Reactome and consistent with nuclear pools. Supporting Evidence: PMID:21249194 CAND1 is predominantly cytoplasmically localized |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8955285 | ACCEPT | Summary: Nucleoplasmic localization linked to displacement of CAND1 from nuclear CRL4; consistent with CAND1 nuclear function. Reason: Consistent with CAND1 acting on nuclear CRLs. Supporting Evidence: PMID:21249194 CAND1 is predominantly cytoplasmically localized |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6798748 | MARK AS OVER ANNOTATED | Summary: Extracellular localization derives from a generic granule-exocytosis Reactome pathway and is not a functional site for this intracellular CRL-assembly factor. Reason: CAND1 is an intracellular cullin regulator; extracellular assignment reflects bulk granule/exocytosis pathway annotation, not biology. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6800434 | MARK AS OVER ANNOTATED | Summary: Extracellular localization from a generic granule-exocytosis Reactome pathway; not a functional site for CAND1. Reason: CAND1 is an intracellular cullin regulator; extracellular assignment is not biologically meaningful here. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5691131 | ACCEPT | Summary: Cytosolic localization where CAND1 binds CUL1; a core compartment. Reason: Consistent with the predominant cytoplasmic localization of CAND1 and its cullin binding. Supporting Evidence: PMID:21249194 CAND1 is predominantly cytoplasmically localized |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8955241 | ACCEPT | Summary: Cytosolic localization where CAND1 binds cytosolic CRL E3 ligases; core compartment. Reason: Consistent with CAND1's predominant cytoplasmic localization and CRL binding. Supporting Evidence: PMID:21249194 CAND1 is predominantly cytoplasmically localized |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8955289 | ACCEPT | Summary: Cytosolic localization linked to displacement of CAND1 from cytosolic CRLs; core compartment. Reason: Consistent with CAND1's predominant cytoplasmic localization and CRL binding. Supporting Evidence: PMID:21249194 CAND1 is predominantly cytoplasmically localized |
| GO:0034774 secretory granule lumen | TAS Reactome:R-HSA-6798748 | MARK AS OVER ANNOTATED | Summary: Secretory granule lumen derives from a bulk granule-exocytosis Reactome pathway and is not a functional location for this cytosolic/nuclear CRL regulator. Reason: Not biologically meaningful for CAND1; reflects bulk pathway-level annotation. |
| GO:1904813 ficolin-1-rich granule lumen | TAS Reactome:R-HSA-6800434 | MARK AS OVER ANNOTATED | Summary: Ficolin-1-rich granule lumen derives from a bulk granule-exocytosis Reactome pathway; not a functional location for CAND1. Reason: Not biologically meaningful for CAND1; reflects bulk pathway-level annotation. |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | MARK AS OVER ANNOTATED | Summary: Detection in exosome proteomics is a high-throughput finding and not a functional localization for this intracellular CRL regulator. Reason: Exosome detection in proteomic surveys does not reflect CAND1's site of action. |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | MARK AS OVER ANNOTATED | Summary: Generic membrane assignment from an NK-cell membrane-proteome survey; not a functional localization for the soluble cytosolic/nuclear CAND1. Reason: Bulk membrane-proteome detection is uninformative and likely co-isolation; CAND1 is not a membrane protein. |
| GO:0005634 nucleus | HDA PMID:21630459 Proteomic characterization of the human sperm nucleus. | ACCEPT | Summary: High-throughput sperm-nucleus proteomic detection; nuclear localization is independently supported for CAND1. Reason: Nuclear localization is genuine for CAND1 (nuclear CRL regulation); consistent with the other accepted nucleus annotations. Supporting Evidence: PMID:21249194 CAND1 is predominantly cytoplasmically localized |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | MARK AS OVER ANNOTATED | Summary: Exosome proteomics detection; not a functional localization for CAND1. Reason: Exosome detection in proteomic surveys does not reflect CAND1's site of action. |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | MARK AS OVER ANNOTATED | Summary: Exosome proteomics detection; not a functional localization for CAND1. Reason: Exosome detection in proteomic surveys does not reflect CAND1's site of action. |
| GO:0005634 nucleus | IDA PMID:21249194 Regulation of cullin RING E3 ubiquitin ligases by CAND1 in v... | ACCEPT | Summary: Nuclear localization is supported; CAND1 also has nuclear pools though it is predominantly cytoplasmic. Reason: Consistent with CAND1 acting on nuclear CRLs; nuclear localization is supported. Supporting Evidence: PMID:21249194 CAND1 is predominantly cytoplasmically localized |
| GO:0005737 cytoplasm | IDA PMID:21249194 Regulation of cullin RING E3 ubiquitin ligases by CAND1 in v... | ACCEPT | Summary: Cytoplasmic localization is the predominant and core localization of CAND1. Reason: Directly demonstrated - CAND1 is predominantly cytoplasmically localized. Supporting Evidence: PMID:21249194 CAND1 is predominantly cytoplasmically localized |
| GO:0010265 SCF complex assembly | IDA PMID:15537541 Structure of the Cand1-Cul1-Roc1 complex reveals regulatory ... | ACCEPT | Summary: Structural study of CAND1-CUL1-ROC1 directly supports CAND1's role in regulating SCF complex assembly. Reason: The crystal structure shows CAND1 clamping CUL1 and blocking the adaptor site, mechanistically explaining its control of SCF assembly. Supporting Evidence: PMID:15537541 forms a tight complex with the Cul1-Roc1 PMID:15537541 occupies the adaptor binding site on |
| GO:0010265 SCF complex assembly | IDA PMID:21249194 Regulation of cullin RING E3 ubiquitin ligases by CAND1 in v... | ACCEPT | Summary: In vivo evidence that CAND1 regulates cullin-RING ligase assembly/activity by promoting substrate-receptor exchange. Reason: CAND1 functions as a positive regulator of CRL activity in vivo via F-box exchange, supporting its role in SCF assembly. Supporting Evidence: PMID:21249194 positive regulator of Cullin ligases in vivo |
| GO:0016567 protein ubiquitination | IDA PMID:15537541 Structure of the Cand1-Cul1-Roc1 complex reveals regulatory ... | ACCEPT | Summary: CAND1 regulates (is involved in) CRL-mediated ubiquitination as an assembly factor; involved_in is appropriate (CAND1 is not catalytic). Reason: Through control of SCF assembly CAND1 modulates substrate ubiquitination; the regulatory involvement is supported. Supporting Evidence: PMID:15537541 regulatory mechanisms for the |
| GO:0016567 protein ubiquitination | IDA PMID:21249194 Regulation of cullin RING E3 ubiquitin ligases by CAND1 in v... | ACCEPT | Summary: CAND1 regulates CRL-mediated ubiquitination in vivo via F-box exchange; involved_in is appropriate. Reason: CAND1 is a positive regulator of CRL ligase activity in vivo, modulating substrate ubiquitination. Supporting Evidence: PMID:21249194 positive regulator of Cullin ligases in vivo |
| GO:0031461 cullin-RING ubiquitin ligase complex | IDA PMID:15537541 Structure of the Cand1-Cul1-Roc1 complex reveals regulatory ... | ACCEPT | Summary: CAND1 forms a defined complex with the CUL1-ROC1 (RBX1) cullin-RING core; part_of the CRL complex (in its unneddylated/exchange-competent state) is supported. Reason: The CAND1-CUL1-ROC1 crystal structure directly demonstrates CAND1 as part of a cullin-RING complex. Supporting Evidence: PMID:15537541 forms a tight complex with the Cul1-Roc1 |
| GO:0031461 cullin-RING ubiquitin ligase complex | IDA PMID:21249194 Regulation of cullin RING E3 ubiquitin ligases by CAND1 in v... | ACCEPT | Summary: CAND1 associates with cullin-RING complexes in vivo (binding unneddylated cullins); part_of is supported. Reason: Cullins are the major CAND1 interactors in cells, consistent with CAND1 being part of cullin-RING complexes. Supporting Evidence: PMID:21249194 cullins are the major |
| GO:0031461 cullin-RING ubiquitin ligase complex | IDA PMID:22405651 The glomuvenous malformation protein Glomulin binds Rbx1 and... | ACCEPT | Summary: CAND1 is part of cullin-RING ligase complexes; consistent with its broad cullin-binding and CRL-regulatory role. Reason: Supported as CAND1 being part of cullin-RING complexes. Supporting Evidence: PMID:21249194 cullins are the major |
| GO:0005515 protein binding | IPI PMID:18826954 SCCRO (DCUN1D1) is an essential component of the E3 complex ... | MARK AS OVER ANNOTATED | Summary: Generic protein-binding annotation from a DCUN1D1/neddylation E3 study; uninformative for CAND1 function. Reason: Bare protein binding is not informative. |
| GO:0005515 protein binding | IPI PMID:12504025 NEDD8 modification of CUL1 dissociates p120(CAND1), an inhib... | MARK AS OVER ANNOTATED | Summary: The underlying interaction is CAND1 binding unneddylated CUL1; captured by specific CRL terms. Bare protein binding is uninformative. Reason: protein binding is too generic; the CAND1-CUL1 interaction is represented by specific terms. |
| GO:0005634 nucleus | IDA PMID:10581176 Induced expression, localization, and chromosome mapping of ... | ACCEPT | Summary: Nuclear (foci/speckle) localization reported in the historical TIP120A study; nuclear localization is independently supported. Reason: Nuclear localization is genuine for CAND1; this early study showed nuclear foci patterns. Supporting Evidence: PMID:10581176 nuclear localization |
| GO:0030154 cell differentiation | IDA PMID:10581176 Induced expression, localization, and chromosome mapping of ... | MARK AS OVER ANNOTATED | Summary: Cell differentiation derives from the historical TIP120A work (expression changes upon differentiation) and is an indirect/correlative association, not the established core CAND1 function. Reason: This reflects TIP120A-era expression correlations, not a direct mechanistic CAND1 role in differentiation. Supporting Evidence: PMID:10581176 differentiation-related gene expression |
| GO:0000151 ubiquitin ligase complex | IDA PMID:12609982 TIP120A associates with cullins and modulates ubiquitin liga... | ACCEPT | Summary: CAND1 (TIP120A) is part of cullin-containing ubiquitin ligase complexes; supported, though more specifically captured by cullin-RING ubiquitin ligase complex. Reason: CAND1 forms complexes with cullins/Rbx1; membership in a ubiquitin ligase complex is supported. Supporting Evidence: PMID:12609982 all cullins tested specifically interacted with TIP120A |
| GO:0016567 protein ubiquitination | IDA PMID:12609982 TIP120A associates with cullins and modulates ubiquitin liga... | ACCEPT | Summary: CAND1 (TIP120A) modulates SCF-mediated ubiquitination (reducing it by blocking Skp1/F-box binding); involved_in is appropriate. Reason: Direct evidence that CAND1 affects SCF ubiquitination of substrate; regulatory involvement is supported. Supporting Evidence: PMID:12609982 TIP120A greatly reduced the ubiquitination of phosphorylated |
| GO:0043086 negative regulation of catalytic activity | IDA PMID:12609982 TIP120A associates with cullins and modulates ubiquitin liga... | ACCEPT | Summary: In its CUL1-bound (unneddylated) state CAND1 negatively regulates SCF catalytic activity by blocking productive assembly; supported, though in vivo CAND1 is a positive regulator of overall CRL activity through exchange. Reason: CAND1 inhibits assembly of productive SCF complexes in vitro (negative regulation of the assembled ligase); a real, mechanistically supported activity. Supporting Evidence: PMID:12609982 negative regulator of SCF E3 ubiquitin ligases |
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Download this section (compressed HTML)Q: How is the apparently contradictory in vitro inhibitory versus in vivo positive (exchange-promoting) role of CAND1 on CRL activity reconciled at the level of individual cullin-RING ligases and substrate receptors?
Suggested experts: Deshaies RJ, Zheng N
Q: To what extent does CAND1 act equivalently across all cullins (CUL1-CUL5) versus having cullin- or receptor-specific exchange preferences?
Suggested experts: Xiong Y
Experiment: Use single-molecule or stopped-flow kinetics with purified CUL1-RBX1, CAND1, and competing fluorescently labeled F-box-SKP1 modules (with and without NEDD8) to measure exchange rates directly.
Hypothesis: CAND1 accelerates F-box receptor exchange on cullin cores with rates that scale with neddylation/deneddylation cycling.
Type: in vitro single-molecule / kinetic exchange assay
Experiment: Quantify the F-box/substrate-receptor proteome and CRL substrate levels by mass spectrometry in CAND1-knockout versus wild-type cells, testing the predicted collapse of receptor diversity.
Hypothesis: CAND1 loss preferentially destabilizes low-abundance F-box receptors by impairing their cycling onto cullin cores.
Type: quantitative proteomics in CAND1-knockout cells
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