Affinage

CAND1

Cullin-associated NEDD8-dissociated protein 1 · UniProt Q86VP6

Length
1230 aa
Mass
136.4 kDa
Annotated
2026-06-09
51 papers in source corpus 33 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CAND1 is a HEAT-repeat scaffold protein that governs the assembly dynamics of cullin-RING ubiquitin ligases (CRLs) by acting as a substrate-receptor exchange factor (PMID:12504025, PMID:23453757). It binds selectively to unneddylated CUL1, forming a ternary complex with CUL1 and ROC1/Rbx1 that excludes the SKP1–F-box adaptor module and inhibits SCF ligase activity in vitro (PMID:12504025, PMID:12504026, PMID:12609982). The crystal structure of the CAND1–CUL1–ROC1 complex resolves the basis of this regulation: CAND1 wraps around CUL1 as a sinuous superhelix, with a beta-hairpin occupying the SKP1-binding site to block F-box recruitment while another region buries the cullin lysine whose neddylation disrupts CAND1 association (PMID:15537541). Rather than acting as a static inhibitor, CAND1 functions catalytically, accelerating dissociation of SCF complexes by roughly one million-fold in the deneddylated state and driving rapid equilibration of CUL1–Rbx1 cores with diverse F-box–SKP1 modules to maintain the cellular SCF repertoire (PMID:23453757, PMID:23535663); cryo-EM intermediates of this reaction capture conformational changes in CUL1/Rbx1 that create an optimized DCNL1-binding site and a partially dissociated state permitting neddylation-driven CAND1 release (PMID:37339624). CAND1 extends its exchange activity to CRL3 via BTB adaptors such as Keap1 (PMID:16449638, PMID:26219975) and to CRL4 via DDB1·DCAF modules, where it acts redundantly with CAND2 (PMID:41864201), while exerting an opposing, inhibitory effect on CRL2 by accelerating disassembly without promoting reassembly (PMID:38177676). Through this control of CRL composition, CAND1 shapes substrate degradation across numerous physiological settings, including p27/Skp2 balance during adipogenesis (PMID:23328082), cardiac calcineurin and Hippo-pathway signaling (PMID:35661710, PMID:40555744), and hepatic lipid metabolism (PMID:37528093). Independently of its CRL role, CAND1 (TIP120) was characterized as a general transcriptional coactivator that stimulates basal transcription by RNA polymerases I, II and III and binds TBP and the shared polymerase subunit RPB5 (PMID:10567521, PMID:11260261).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1999 High

    Before its CRL role was known, CAND1/TIP120 was characterized biochemically as a transcriptional coactivator, establishing its first ascribed molecular function.

    Evidence Reconstituted in vitro transcription assays, EMSA and GST pulldown showing stimulation of RNAP I/II/III and binding to TBP and RPB5

    PMID:10567521 PMID:11260261

    Open questions at the time
    • No structural basis for TBP/RPB5 binding
    • Relationship between transcriptional and CRL functions undefined
    • In vivo transcriptional targets not mapped
  2. 1999 Low

    Early proteomic identification placed CAND1 in a large TBP/proteasomal-ATPase-containing assembly, an observation that has not been mechanistically integrated.

    Evidence TBP pulldown, far-Western and protein microsequencing identifying an ~800 kDa complex

    PMID:10526239

    Open questions at the time
    • Single pulldown-based identification without functional follow-up
    • Significance of proteasomal ATPase association unknown
  3. 2002 High

    The pivotal reframing of CAND1 came when it was shown to bind specifically unneddylated CUL1, displace SKP1, and inhibit SCF activity, linking it to the ubiquitin-proteasome system and defining its neddylation-gated cullin interaction.

    Evidence Reciprocal Co-IP, in vitro ubiquitin ligase assays and siRNA knockdown, independently replicated in parallel papers

    PMID:12504025 PMID:12504026

    Open questions at the time
    • Whether CAND1 was an inhibitor or a positive regulator of CRL turnover unresolved
    • Structural basis of selectivity unknown at this stage
  4. 2003 High

    CAND1 was shown to interact with multiple cullins and to block both adaptor binding and cullin neddylation, broadening its scope beyond CUL1 and defining the neddylation-blocking mechanism.

    Evidence Immunopurification/MS, in vitro ubiquitination and neddylation assays with deletion mapping across several cullins

    PMID:12609982 PMID:12684064 PMID:12706828

    Open questions at the time
    • Whether constitutive inhibition reflected the physiological role unclear
    • Domain requirements only partially mapped
  5. 2004 High

    The crystal structure resolved how CAND1 simultaneously blocks adaptor recruitment and is regulated by neddylation, providing the structural logic for its selectivity.

    Evidence X-ray crystallography of CAND1–CUL1–ROC1 with biochemical validation

    PMID:15537541

    Open questions at the time
    • Static structure did not reveal exchange kinetics or intermediates
    • Did not address how SKP1-F-box modules outcompete CAND1 in cells
  6. 2005 Medium

    CAND1 was connected to the deneddylation machinery, shown to bind CUL1 mutually exclusively with the CSN yet facilitate CSN-mediated deneddylation, integrating it into the neddylation cycle.

    Evidence Co-IP, siRNA knockdown and in vitro deneddylation assay

    PMID:16036220

    Open questions at the time
    • Mechanism coupling CAND1 binding to CSN catalysis not defined
    • Single lab
  7. 2009 Medium

    Genetic dissection in fungi reframed CAND1's role from a stoichiometric inhibitor to a balancer of CRL complex composition, showing it prevents abundant adaptors from monopolizing cullin cores.

    Evidence Genetic deletion, stability assays and Co-IP in S. pombe; genetic complementation and neddylation assays in S. cerevisiae (Lag2)

    PMID:19748355 PMID:19942853

    Open questions at the time
    • Mammalian relevance not yet demonstrated
    • Quantitative exchange mechanism not measured
  8. 2010 Medium

    Metazoan loss-of-function studies established CAND1 as a negative regulator of cullin neddylation in vivo with differential requirements across CRLs, connecting it to developmental signaling.

    Evidence In vivo Co-IP and genetic epistasis in C. elegans (CUL-2/CUL-4) and Drosophila (Cul3/HIB/Ci)

    PMID:20659444 PMID:20691177

    Open questions at the time
    • Why CAND1 requirement differs among cullins unexplained
    • Single-lab studies per organism
  9. 2011 Medium

    Additional regulatory inputs to CAND1–cullin engagement were identified, and quantitative analysis revealed CAND1 binds CUL1 weakly in vivo, anticipating a catalytic rather than stoichiometric model.

    Evidence Co-IP and displacement assays for COMMD1; subcellular fractionation and quantitative Co-IP in mammalian cells

    PMID:21249194 PMID:21778237

    Open questions at the time
    • Quantitative discrepancy with inhibitor model unresolved at the time
    • Single studies
  10. 2013 High

    Real-time kinetics and quantitative proteomics defined CAND1's true function as a catalytic exchange factor that accelerates F-box module swapping a million-fold, reconciling earlier inhibitor observations and explaining how cells remodel the CRL1 landscape.

    Evidence Real-time kinetic measurements, in vitro reconstitution, cell depletion with quantitative MS, and yeast genetics coupling CSN deneddylation to CAND1-driven adaptor release

    PMID:23328082 PMID:23453757 PMID:23535662 PMID:23535663

    Open questions at the time
    • Structural intermediates of the exchange cycle not yet resolved
    • Scope across CRL families not fully tested
  11. 2015 Medium

    CAND1 was shown to act as an exchange factor for CRL3 adaptors during a defined physiological program, extending the exchange model beyond SCF.

    Evidence siRNA and miRNA perturbation with Co-IP during adipogenesis (Keap1-Cul3)

    PMID:26219975

    Open questions at the time
    • Single lab
    • Kinetic parameters for CRL3 exchange not measured
  12. 2023 High

    Cryo-EM captured the full exchange trajectory, revealing receptor-dissociation and CAND1-dissociation intermediates and a role for DCNL1, providing a dynamic structural mechanism for the catalytic cycle.

    Evidence Cryo-EM with in vitro reconstitution and biochemical validation of CAND1-driven SCF exchange

    PMID:37339624

    Open questions at the time
    • Whether the same intermediates apply to CRL2/3/4 unknown
    • Timescale linkage to in-cell dynamics not directly shown
  13. 2024 High

    CAND1 was found to act oppositely on CRL2, accelerating disassembly without promoting reassembly, revealing that its directional output depends on the cullin and giving a handle on selective degradation pacing.

    Evidence In vitro kinetic binding assays and PROTAC-based degradation assays in human cells

    PMID:38177676

    Open questions at the time
    • Molecular determinant of inhibitory vs activating behavior across cullins undefined
    • Single lab
  14. 2026 Medium

    Quantitative kinetics established that CAND1 (and redundantly CAND2) drives DDB1·DCAF exchange on CRL4, completing the picture of CAND1 acting across major CRL families.

    Evidence Genetic perturbation, real-time kinetics and quantitative interaction proteomics on CRL4 complexes

    PMID:41864201

    Open questions at the time
    • Functional consequences for specific CRL4 substrates not detailed
    • Basis for CAND1/CAND2 divergence on CRL1 vs CRL4 unexplained

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how CAND1's exchange-factor activity is mechanistically reconciled with its CRL-independent functions (transcriptional coactivation, ER tubule/lunapark regulation) and what determines its cullin-specific switch between activating and inhibitory outcomes.
  • No structural or kinetic model unifying transcription and CRL roles
  • Determinants of CRL2-inhibitory vs CRL1-activating directionality unknown
  • Physiological disease links rest on single-lab in vivo models

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 6 GO:0060090 molecular adaptor activity 3 GO:0140110 transcription regulator activity 2
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 1
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-74160 Gene expression (Transcription) 2
Partners
COMMD1CUL1DCNL1KEAP1RBX1RPB5SKP1TBP
Complex memberships
CAND1-CUL1-ROC1/Rbx1 complexCRL3 (Keap1-Cul3)CRL4 (DDB1-DCAF)SCF (CRL1)

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 CAND1 (p120) selectively binds to unneddylated CUL1 and is dissociated by CUL1 neddylation. CAND1 forms a ternary complex with CUL1 and ROC1, dissociates SKP1 from CUL1, and inhibits SCF ligase activity in vitro. Suppression of CAND1 in vivo increased the CUL1-SKP1 complex level. Co-immunoprecipitation, in vitro ubiquitin ligase assay, siRNA knockdown Molecular cell High 12504025
2002 CAND1 binds to unneddylated CUL1 independently of SKP1 and F-box proteins. Neddylation of CUL1 or presence of SKP1 and ATP causes CAND1 dissociation, promoting SCF complex assembly and F-box protein incorporation, which leads to their destabilization. Co-immunoprecipitation, in vitro binding assay, cell fractionation Molecular cell High 12504026
2003 TIP120A (CAND1) interacts with all cullins tested (not just CUL1), forms a complex with CUL1 and Rbx1 but interferes with binding of Skp1 and F-box proteins to CUL1, and greatly reduces ubiquitination of phosphorylated IκBα by SCF(β-TrCP) ubiquitin ligase. Immunopurification from HeLa cells, mass spectrometry, immunoprecipitation, in vitro ubiquitination assay The Journal of biological chemistry High 12609982
2003 TIP120A (CAND1) physically associates with CUL1 in the nucleus via a central region of CUL1 distinct from its binding sites for Skp1 and Rbx1, and interacts selectively with CUL1 not modified by NEDD8. The CUL1-TIP120A complex does not include Skp1. Tandem affinity purification, immunoprecipitation, immunoblot, immunofluorescence Biochemical and biophysical research communications Medium 12684064
2003 TIP120A (CAND1) binds to unneddylated CUL1 but not neddylated CUL1. Binding requires both the N-terminal stalk and C-terminal globular domain of CUL1. TIP120A efficiently inhibits neddylation of CUL1 but does not affect substrate-independent ubiquitination by CUL1/Rbx1, implying it blocks access of Nedd8 to the conjugation site. Co-immunoprecipitation, in vitro neddylation assay, deletion mapping FEBS letters Medium 12706828
2004 Crystal structure of the Cand1-Cul1-Roc1 complex shows Cand1 adopts a sinuous HEAT-repeat superhelical structure clamping around Cul1. A Cand1 beta-hairpin partially occupies the Skp1 adaptor binding site on Cul1, blocking F-box protein recruitment. At the other end, Cand1 HEAT repeats bury a Cul1 lysine residue whose neddylation blocks Cand1-Cul1 association. X-ray crystallography, biochemical binding assays Cell High 15537541
2005 CAND1 and COP9 signalosome (CSN) bind to unneddylated CUL1 in a mutually exclusive manner. CAND1 inhibits CSN binding to CUL1 but greatly facilitates CSN-mediated deneddylation of CUL1 in vitro in a manner dependent on CAND1's binding to CUL1. siRNA knockdown of CAND1 enhanced the CUL1-CSN interaction. Co-immunoprecipitation, siRNA knockdown, in vitro deneddylation assay Biochemical and biophysical research communications Medium 16036220
2006 CAND1 regulates the Keap1-Cul3 E3 ligase complex: ectopic CAND1 overexpression decreased Keap1-Cul3 association, while siRNA knockdown of CAND1 increased it. Both overexpression and knockdown decreased Keap1-mediated Nrf2 ubiquitination and degradation, demonstrating that proper CAND1-mediated substrate adaptor recycling is required for efficient Nrf2 repression. siRNA knockdown, ectopic overexpression, co-immunoprecipitation, ubiquitination assay Molecular and cellular biology Medium 16449638
1999 TIP120 (CAND1) stimulates basal transcription from RNA polymerase I, II, and III promoters in a reconstituted system. It functions during preinitiation complex formation at the step of RNAP II/TFIIF recruitment. TIP120 binds TBP and RPB5 (a common subunit of all three RNA polymerases) in vitro. Reconstituted in vitro transcription assay, EMSA, deletion analysis, GST pulldown Molecular and cellular biology High 10567521
1999 TIP120A (CAND1) is part of an ~800 kDa complex containing TBP and proteasomal ATPases (SUG1, S4, MSS1, TBP1, TBP7, SUG2), as identified by pull-down and far-Western analysis. TBP pulldown, far-Western, 2D electrophoresis, protein microsequencing Genes to cells Low 10526239
2001 TIP120A (CAND1) has bipartite TBP-binding domains: both the acidic N-terminal region and the leucine-rich C-terminal region bind TBP and independently stimulate basal transcription in vitro, and also facilitate nonspecific DNA-binding of RNA polymerase II. Truncation/deletion analysis, in vitro transcription assay, binding assay Genes to cells Medium 11260261
2009 In fission yeast, CAND1 does not control adaptor (F-box protein) stability but maintains the cellular balance of CRL1 complexes by preventing rare F-box proteins from being outcompeted for CUL1 binding by more abundant adaptors. CSN-sensitive F-box proteins require the CSN for stability, not CAND1. Genetic deletion, protein stability assays, co-immunoprecipitation in S. pombe Molecular cell Medium 19748355
2009 Yeast Lag2 is a S. cerevisiae orthologue of CAND1 that binds non-neddylated Cdc53 and prevents its neddylation in vivo and in vitro. Binding uses a conserved C-terminal beta-hairpin that inserts into the Skp1-binding pocket and an N-terminal motif covering the neddylation lysine. Genetic complementation, in vitro binding, neddylation assay, domain mapping The EMBO journal Medium 19942853
2010 C. elegans CAND-1 physically interacts with CUL-2 and CUL-4 in vivo. In cand-1 mutants, neddylated isoforms of CUL-2 and CUL-4 are increased, indicating CAND-1 is a negative regulator of cullin neddylation. cand-1 mutants share phenotypes with cul-1 and lin-23 mutants (including accumulation of SCF(LIN-23) target GLR-1), suggesting CAND-1 is differentially required for distinct CRL complexes. Co-immunoprecipitation in vivo, genetic analysis of loss-of-function mutants, immunoblot for neddylation Developmental biology Medium 20659444
2010 Drosophila Cand1 loss causes accumulation of neddylated Cullin3 and stabilizes the Cul3 adaptor protein HIB, and stimulates degradation of Cubitus interruptus (Ci) through enhanced Cul3-RING ligase activity. Cand1 stabilizes unneddylated Cul3 by preventing its proteasomal degradation, shifting the equilibrium away from Cul3 neddylation. Drosophila genetic mutant analysis, immunoblot, epistasis with neddylation pathway mutants Developmental biology Medium 20691177
2011 COMMD1 interacts with multiple cullins and the COMMD1-Cul2 complex cannot bind CAND1. COMMD1 can actively displace CAND1 from CRLs, thereby antagonizing CAND1 binding and promoting CRL activation. Co-immunoprecipitation, displacement assay The Journal of biological chemistry Medium 21778237
2011 CAND1 is predominantly cytoplasmically localized in mammalian cells and cullins are its major interacting proteins. However, only small amounts of CAND1 bind to Cul1 in vivo, and binding of CAND1 to Cul1 in vivo is weak compared to F-box protein substrate receptors. Preventing F-box protein binding to Cul1 does not increase CAND1 binding. Subcellular fractionation, co-immunoprecipitation, quantitative binding analysis in mammalian cells PloS one Medium 21249194
2012 CAND1 was identified as a novel centrosomal protein that synergizes with PLK4 to induce centriole overduplication. CAND1 functions in this process by increasing PLK4 protein stability. CUL1 mutants that cannot interact with CAND1 and cannot assemble functional E3 complexes fail to restrain aberrant daughter centriole synthesis. Immunofluorescence, overexpression, co-expression assays, protein stability measurement Neoplasia Low 23019411
2012 The EBV tegument protein BPLF1 binds to cullins via helix-2 interacting with helix-23 of the cullin CTD, at the site used for electrostatic interaction with CAND1 helix-8. This binding inhibits CAND1 recruitment to deneddylated CRLs. CAND1 overexpression rescues cullin proteolysis caused by BPLF1. Co-immunoprecipitation, mutagenesis, rescue experiment with CAND1 overexpression Journal of molecular cell biology Medium 22474075
2013 Cand1 is a protein exchange factor that augments SCF(Fbxw7) dissociation by one-million-fold in the Nedd8-deconjugated state. Cand1 accelerates the rate at which Cul1-Rbx1 equilibrates with multiple F-box protein-Skp1 modules. Depletion of Cand1 from cells impedes recruitment of new F-box proteins to pre-existing Cul1 and profoundly alters the cellular SCF landscape. Real-time kinetic measurements, binding assays, ubiquitylation assays, cell depletion experiments with quantitative proteomics Cell High 23453757
2013 In budding yeast, CAND1 promotes substrate adaptor release from SCF following deneddylation by CSN during metabolic shifts. CSN- or CAND1-mutant cells fail to release substrate adaptors, delay new complex formation during SCF reactivation, and exhibit substrate degradation defects. Yeast genetics, co-immunoprecipitation, substrate degradation assays Nature communications High 23535662
2013 Using quantitative mass spectrometry, CAND1 was shown to control in vivo CRL1 network dynamics by promoting assembly of newly synthesized F-box containing substrate receptors with CUL1-RBX1 cores. In vitro, CAND1 can displace F-box proteins from Cul1, functioning in a cycle that exchanges F-box proteins on CUL1 cores to maintain the CRL1 landscape. Quantitative mass spectrometry, in vitro biochemical displacement assay Nature communications High 23535663
2013 CAND1 preferentially blocks integration of Skp2 into CRL1s. Suppression of CAND1 in HeLa cells increases Skp2 assembly into CRL1s and reduces p27 levels; CAND1 overexpression elevates p27. CAND1-dependent control of Skp2-CRL1 assembly is independent of CSN, as shown in CSN1 knockdown cells. CAND1 and p27 levels increase coordinately during adipogenesis, and CAND1 knockdown reduces p27 and blocks adipogenesis. siRNA knockdown, ectopic overexpression, co-immunoprecipitation, immunoblot, adipogenesis differentiation assay Biochimica et biophysica acta Medium 23328082
2015 CAND1 acts as an exchange factor for CRL3 complexes: silencing CAND1 decreases and impairs Keap1 integration into Cul3-RING ubiquitin ligases during adipogenesis. CAND1 overexpression via miRNA148a transfection also reduces Keap1 levels and retards adipogenesis. siRNA knockdown, miRNA transfection, co-immunoprecipitation, differentiation assay The international journal of biochemistry & cell biology Medium 26219975
2019 CAND1 was identified as a lunapark (Lnp)-binding protein by affinity chromatography. CAND1 and Lnp form a higher-molecular-weight complex in vitro. CAND1 reduces the auto-ubiquitination activity of Lnp. CAND1 knockdown enhances proteasomal degradation of Lnp and reduces the tubular ER network. Affinity chromatography, in vitro complex formation assay, auto-ubiquitination assay, siRNA knockdown, fluorescence microscopy Scientific reports Medium 31511573
2022 CAND1 overexpression favors assembly of Cul1/atrogin1/calcineurin complex and promotes ubiquitination and degradation of calcineurin. CAND1 deficiency upregulates calcineurin expression in vivo and in vitro. CAND1 deficiency-induced cardiac hypertrophic phenotypes were partially rescued by calcineurin knockdown. Transgenic and knockout mice, siRNA knockdown, overexpression, co-immunoprecipitation, ubiquitination assay, cardiac phenotyping Pharmacological research Medium 35661710
2023 Cryo-EM structural analysis of the CAND1-driven SCF substrate receptor exchange reaction revealed high-resolution intermediates including a ternary CAND1-SCF complex, SR-dissociation intermediates, and CAND1-dissociation intermediates. CAND1-induced conformational changes in CUL1/RBX1 provide an optimized DCNL1-binding site; DCNL1 plays a dual role in CAND1-SCF dynamics. A partially dissociated CAND1-SCF conformation accommodates cullin neddylation leading to CAND1 displacement. Cryo-EM structural determination, in vitro reconstitution, biochemical assays Molecular cell High 37339624
2023 CAND1 deficiency enhances assembly of Cullin1, FBXO42, and ACAA2 complexes, thereby promoting ubiquitinated degradation of ACAA2. Hepatocyte-specific CAND1 knockout exacerbates HFD-induced liver injury while CAND1 knockin ameliorates it. ACAA2 overexpression abolishes the exacerbated effects of CAND1 deficiency on NAFLD. Hepatocyte-specific knockout and knockin mouse models, co-immunoprecipitation, ubiquitination assay, rescue experiment Nature communications Medium 37528093
2024 CAND1 inhibits CRL2-mediated protein degradation in human cells, contrasting its activating role on CRL1. CAND1 dramatically increases the dissociation rate of CRL2s but barely accelerates their reassembly. Using PROTACs with different substrate affinities for CRL2VHL, CAND1's inhibitory effect was shown to help distinguish target proteins with different affinities, providing a mechanism for selective protein degradation pacing. In vitro kinetic binding assays, PROTAC-based degradation assays in human cells, genetic perturbation Nature structural & molecular biology High 38177676
2025 CAND1 promotes assembly of Cullin1/FBXW11/Mob1b complexes, enhancing K48-linked ubiquitination of Mob1b at K108, leading to Mob1b degradation and suppression of the Hippo pathway to facilitate cardiomyocyte proliferation. Cardiac-specific CAND1 overexpression improved heart regeneration after myocardial infarction; CAND1 deficiency blunted neonatal heart regeneration. Transgenic mice, cardiac-specific knockout, mass spectrometry, co-immunoprecipitation, ubiquitination assay with K48 ubiquitin linkage mapping, rescue experiment with Mob1b deletion Cell death and differentiation Medium 40555744
2025 CAND1 directly interacts with HER2 and stabilizes HER2 protein expression. The E3 ligase CUL7 promotes HER2 ubiquitination and is essential for the CAND1-HER2 interaction. CAND1 knockdown enhances CUL7 neddylation, activating its ligase activity and leading to HER2 ubiquitination. HER2 overexpression reverses the growth inhibition caused by CAND1 loss. Co-immunoprecipitation, immunofluorescence, western blot, ubiquitination assay, xenograft model, rescue overexpression Breast cancer research Medium 41310794
2026 Both CAND1 and CAND2 promote CRL4-mediated protein degradation and enhance dynamic exchange of DDB1·DCAF substrate receptor modules. In contrast to their differential efficiencies in CRL1 disassembly (CAND2 being less efficient), CAND1 and CAND2 exhibit similar kinetic parameters and comparable exchange efficiencies across most CRL4 complexes. Genetic perturbation, real-time kinetic analyses, quantitative interaction proteomics Structure Medium 41864201
2026 CAND1 was identified as an AR/ARv7 coactivator via DNA pulldown assay. CAND1 knockdown in prostate cancer cells reduced expression of AR and ARv7 target genes. DNA-PK phosphorylates AR and ARv7 and stabilizes CAND1 interactions within the AR-coregulator complex. Cell-free DNA pulldown assay, mass spectrometry, siRNA knockdown, gene expression analysis PloS one Low 42133602

Source papers

Stage 0 corpus · 51 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 NEDD8 modification of CUL1 dissociates p120(CAND1), an inhibitor of CUL1-SKP1 binding and SCF ligases. Molecular cell 270 12504025
2002 CAND1 binds to unneddylated CUL1 and regulates the formation of SCF ubiquitin E3 ligase complex. Molecular cell 261 12504026
2004 Structure of the Cand1-Cul1-Roc1 complex reveals regulatory mechanisms for the assembly of the multisubunit cullin-dependent ubiquitin ligases. Cell 240 15537541
2013 Cand1 promotes assembly of new SCF complexes through dynamic exchange of F box proteins. Cell 219 23453757
2010 miR-148a is an androgen-responsive microRNA that promotes LNCaP prostate cell growth by repressing its target CAND1 expression. Prostate cancer and prostatic diseases 125 20820187
2009 F-box-directed CRL complex assembly and regulation by the CSN and CAND1. Molecular cell 107 19748355
2013 CAND1 controls in vivo dynamics of the cullin 1-RING ubiquitin ligase repertoire. Nature communications 100 23535663
2013 CSN- and CAND1-dependent remodelling of the budding yeast SCF complex. Nature communications 91 23535662
2006 CAND1-mediated substrate adaptor recycling is required for efficient repression of Nrf2 by Keap1. Molecular and cellular biology 90 16449638
2003 TIP120A associates with cullins and modulates ubiquitin ligase activity. The Journal of biological chemistry 63 12609982
2003 Preferential interaction of TIP120A with Cul1 that is not modified by NEDD8 and not associated with Skp1. Biochemical and biophysical research communications 53 12684064
2012 CAND1 promotes PLK4-mediated centriole overduplication and is frequently disrupted in prostate cancer. Neoplasia (New York, N.Y.) 47 23019411
2011 COMMD1 (copper metabolism MURR1 domain-containing protein 1) regulates Cullin RING ligases by preventing CAND1 (Cullin-associated Nedd8-dissociated protein 1) binding. The Journal of biological chemistry 36 21778237
1999 TATA-Binding protein-interacting protein 120, TIP120, stimulates three classes of eukaryotic transcription via a unique mechanism. Molecular and cellular biology 35 10567521
2005 CAND1 enhances deneddylation of CUL1 by COP9 signalosome. Biochemical and biophysical research communications 34 16036220
1999 Multiple mammalian proteasomal ATPases, but not proteasome itself, are associated with TATA-binding protein and a novel transcriptional activator, TIP120. Genes to cells : devoted to molecular & cellular mechanisms 33 10526239
1999 TIP120B: a novel TIP120-family protein that is expressed specifically in muscle tissues. Biochemical and biophysical research communications 31 10441524
2010 C. elegans CAND-1 regulates cullin neddylation, cell proliferation and morphogenesis in specific tissues. Developmental biology 30 20659444
2003 TIP120A associates with unneddylated cullin 1 and regulates its neddylation. FEBS letters 29 12706828
2017 miR-33a inhibits cell proliferation and invasion by targeting CAND1 in lung cancer. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 28 28871425
2009 Cullin neddylation and substrate-adaptors counteract SCF inhibition by the CAND1-like protein Lag2 in Saccharomyces cerevisiae. The EMBO journal 28 19942853
2023 ASCC3 promotes the immunosuppression and progression of non-small cell lung cancer by impairing the type I interferon response via CAND1-mediated ubiquitination inhibition of STAT3. Journal for immunotherapy of cancer 25 38148115
2013 CAND1-dependent control of cullin 1-RING Ub ligases is essential for adipogenesis. Biochimica et biophysica acta 25 23328082
2023 Cullin-associated and neddylation-dissociated protein 1 (CAND1) alleviates NAFLD by reducing ubiquitinated degradation of ACAA2. Nature communications 24 37528093
2012 Herpes virus deneddylases interrupt the cullin-RING ligase neddylation cycle by inhibiting the binding of CAND1. Journal of molecular cell biology 24 22474075
2011 Regulation of cullin RING E3 ubiquitin ligases by CAND1 in vivo. PloS one 24 21249194
2022 GSTM3 deficiency impedes DNA mismatch repair to promote gastric tumorigenesis via CAND1/NRF2-KEAP1 signaling. Cancer letters 22 35487311
2023 Structural and mechanistic insights into the CAND1-mediated SCF substrate receptor exchange. Molecular cell 19 37339624
2020 The Impact of Cand1 in Prostate Cancer. Cancers 18 32059441
2015 CAND1 exchange factor promotes Keap1 integration into cullin 3-RING ubiquitin ligase during adipogenesis. The international journal of biochemistry & cell biology 18 26219975
2009 Resolving the CSN and CAND1 paradoxes. Molecular cell 17 19748350
2018 Targeting CAND1 promotes caspase-8/RIP1-dependent apoptosis in liver cancer cells. American journal of translational research 16 29887951
2010 Drosophila Cand1 regulates Cullin3-dependent E3 ligases by affecting the neddylation of Cullin3 and by controlling the stability of Cullin3 and adaptor protein. Developmental biology 16 20691177
2017 Small molecule perturbation of the CAND1-Cullin1-ubiquitin cycle stabilizes p53 and triggers Epstein-Barr virus reactivation. PLoS pathogens 12 28715492
2013 Set them free: F-box protein exchange by Cand1. Cell research 12 23609796
2011 Neddylation and CAND1 independently stimulate SCF ubiquitin ligase activity in Candida albicans. Eukaryotic cell 11 22080453
2022 Cullin-associated and neddylation-dissociated 1 protein (CAND1) governs cardiac hypertrophy and heart failure partially through regulating calcineurin degradation. Pharmacological research 10 35661710
2001 TBP-interacting protein TIP120A is a new global transcription activator with bipartite functional domains. Genes to cells : devoted to molecular & cellular mechanisms 9 11260261
2019 CAND1 regulates lunapark for the proper tubular network of the endoplasmic reticulum. Scientific reports 8 31511573
2021 LncRNA RMRP knockdown promotes proliferation and migration of Schwann cells by mediating the miR-766-5p/CAND1 axis. Neuroscience letters 7 34974108
2013 Cullins getting undressed by the protein exchange factor Cand1. Cell 6 23540687
2024 CAND1 inhibits Cullin-2-RING ubiquitin ligases for enhanced substrate specificity. Nature structural & molecular biology 4 38177676
2023 CAND1 orchestrates CRLs through rock and roll. Cell 4 37116466
2025 Cullin-associated and neddylation-dissociated protein 1 (CAND1) promotes cardiomyocyte proliferation and heart regeneration by enhancing the ubiquitinated degradation of Mps one binder kinase activator 1b (Mob1b). Cell death and differentiation 3 40555744
2020 Dynamically Expressed miR-BART16 Functions as a Suppressor of CAND1 in Infectious Mononucleosis Caused by Epstein-Barr Virus in Children. Annals of clinical and laboratory science 2 32581028
2023 The long non-coding RNA transcript, LOC100130460 (CAND1.11) gene, encodes a novel protein highly expressed in cancer cells and tumor human testis tissues. Cancer biomarkers : section A of Disease markers 1 37661873
2023 Inhibition of miR-29a-3p Alleviates Apoptosis of Lens Epithelial Cells via Upregulation of CAND1. Current eye research 1 38095165
2026 CAND1 and CAND2 drive CUL4 substrate receptor exchange with largely comparable biochemical efficiency, unlike their relative effects on CUL1. Structure (London, England : 1993) 0 41864201
2026 Identification of CAND1 as a DNA-dependent protein kinase-regulated coactivator of androgen receptor and the ARv7 splice variant. PloS one 0 42133602
2025 NEDD8-specific protease 1 deficiency as a novel driver of hepatoblastoma development through dysregulation of the CAND1-NEDD8 pathway. Hepatology (Baltimore, Md.) 0 41236496
2025 CAND1 mediates CUL7-dependent HER2 protein stability to drive breast cancer progression. Breast cancer research : BCR 0 41310794

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