Affinage

CUL3

Cullin-3 · UniProt Q13618

Length
768 aa
Mass
88.9 kDa
Annotated
2026-04-28
100 papers in source corpus 49 papers cited in narrative 48 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CUL3 is a scaffold cullin protein that assembles with RBX1/ROC1 RING-finger protein and a large, diverse family of BTB-domain-containing substrate adaptors to form Cullin-RING E3 ubiquitin ligase (CRL3) complexes that ubiquitinate specific substrates for proteasomal degradation or non-degradative signaling. BTB-domain proteins such as KEAP1, SPOP, KLHL3, KLHL9/13, KLHL20, KLHL21, and KLHL25 each serve as exchangeable substrate-recognition modules that bridge CUL3 to distinct targets—including NRF2 (oxidative stress response), Aurora B (mitotic chromosome-to-midzone translocation and cytokinesis), WNK kinases (renal ion homeostasis), ULK1/Beclin-1 (autophagy termination), cyclin E (cell cycle control), ACLY (fatty acid metabolism), eIF4G1 (cap-dependent translation in neurons), and GluR6/GLR-1 (synaptic glutamate receptor turnover)—thereby governing an exceptionally broad substrate repertoire (PMID:13679922, PMID:15572695, PMID:17543862, PMID:26687681, PMID:23387299, PMID:34491895, PMID:31780330, PMID:17062563). CRL3 activity is positively regulated by NEDD8 conjugation to CUL3 and negatively regulated by COP9 signalosome-mediated deneddylation; cycling between these states is essential for sustained ligase function and CUL3 protein stability (PMID:12781129, PMID:16127432). Disease-causing mutations in CUL3 or its adaptors KLHL3 and KLHL7 disrupt CRL3 complex assembly or substrate ubiquitination, causing familial hyperkalemic hypertension (pseudohypoaldosteronism type II) and autosomal-dominant retinitis pigmentosa, respectively (PMID:23387299, PMID:21828050, PMID:34878901).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2001 Medium

    Establishing that CUL3, together with the RING-finger protein ROC1, possesses intrinsic E3 ubiquitin ligase activity answered whether CUL3 could directly catalyze ubiquitin conjugation, positioning it as a functional cullin scaffold.

    Evidence In vitro ubiquitination of cyclin D1 by ROC1-CUL3 immunocomplexes with RING mutant controls

    PMID:11311237

    Open questions at the time
    • No substrate adaptor identified
    • Physiological relevance of cyclin D1 ubiquitination by CUL3 not confirmed in vivo
  2. 2003 High

    Identification of BTB-domain proteins as substrate-specific adaptors for CUL3—analogous to F-box proteins for CUL1—resolved the fundamental question of how CUL3 recognizes its substrates, establishing the modular CRL3 architecture.

    Evidence Biochemical reconstitution, genetic epistasis, and two-hybrid screens in C. elegans showing MEL-26 bridges CUL3 to MEI-1/katanin

    PMID:13679921 PMID:13679922

    Open questions at the time
    • Structural basis of BTB-CUL3 interaction unknown at this point
    • Scope of BTB adaptor diversity not yet defined
  3. 2003 High

    Demonstrating that CUL3 neddylation/deneddylation cycling is required for in vivo E3 activity established the central regulatory switch controlling CRL3 function.

    Evidence RNAi epistasis and biochemical assays in C. elegans showing both NEDD8 conjugation and COP9-mediated removal are needed for MEI-1 degradation

    PMID:12781129

    Open questions at the time
    • Mechanistic basis of how neddylation activates CRL3 not structurally resolved
    • Whether cycling requirement is universal across CRL3 complexes unclear
  4. 2004 High

    Identification of KEAP1 as a CUL3 adaptor targeting NRF2 for ubiquitination, with electrophile sensing through Cys151, established the paradigmatic CRL3-KEAP1-NRF2 oxidative stress pathway and showed how adaptor modification regulates CRL3 activity.

    Evidence In vitro reconstituted ubiquitination, co-immunoprecipitation, Cys151 mutagenesis, and oxidative stress perturbation in two independent labs

    PMID:15367669 PMID:15572695

    Open questions at the time
    • Structural basis of KEAP1-CUL3 interface not yet determined
    • Mechanism of Cys151 modification-induced dissociation from CUL3 not fully resolved
  5. 2005 High

    Showing that COP9 signalosome deneddylation maintains CUL3 protein stability—neddylated CUL3 is inherently unstable—revealed that the neddylation cycle is required not just for activity but for CUL3 homeostasis.

    Evidence CSN mutant cells with CUL3 protein stability assays and unneddylatable mutant analysis

    PMID:16127432

    Open questions at the time
    • Degradation pathway of neddylated CUL3 not identified
    • Whether this applies to all tissue contexts unknown
  6. 2006 High

    Discovery that CRL3 complexes with different BTB-Kelch adaptors regulate neuronal glutamate receptor levels (GluR6 via actinfilin, GLR-1 via KEL-8) extended CUL3 function beyond cell cycle control into synaptic biology.

    Evidence Co-immunoprecipitation, ubiquitination assays, and neuronal loss-of-function studies in mammalian hippocampal neurons and C. elegans

    PMID:16394099 PMID:17062563

    Open questions at the time
    • Specific ubiquitin chain types on glutamate receptors not characterized
    • Whether receptor ubiquitination leads to degradation vs. endosomal sorting unclear
  7. 2007 High

    Demonstration that CUL3-KLHL9/13 ubiquitylates Aurora B to drive its removal from mitotic chromosomes for cytokinesis, and that CUL3 loss causes cyclin E accumulation and polyploidy, established CUL3 as a critical mitotic and cell cycle regulator.

    Evidence Reconstituted in vitro ubiquitination, RNAi phenotyping of mitotic defects, and conditional Cul3 knockout mouse with cyclin E and ploidy readouts

    PMID:17339333 PMID:17543862

    Open questions at the time
    • BTB adaptor for cyclin E not identified
    • Relative contributions of multiple CRL3 complexes to mitotic regulation unclear
  8. 2009 High

    Structural determination of the SPOP-CUL3 and KLHL11-CUL3 interfaces revealed the molecular grammar of BTB adaptor-cullin recognition—including the 3-box motif and N-terminal extension—explaining how diverse BTB proteins engage a common CUL3 scaffold.

    Evidence Crystal structures of SPOP BTB-3box and KLHL11 BTB-BACK with CUL3 N-terminal domain, quantitative binding assays, and mutagenesis

    PMID:19818708 PMID:23349464

    Open questions at the time
    • Full-length CRL3 holo-complex structure not available
    • How dimerization of BTB adaptors allosterically influences CUL3 conformation unknown
  9. 2009 High

    Showing that DCNL3 promotes CUL3 neddylation at the plasma membrane established that neddylation can be spatially regulated, linking CRL3 activation to specific subcellular compartments.

    Evidence RNAi with neddylation readout, subcellular fractionation, plasma membrane localization of DCNL3

    PMID:19617556

    Open questions at the time
    • Whether other DCNLs provide compartment-specific neddylation of CUL3 untested
    • Substrates of membrane-localized CRL3 not identified
  10. 2013 High

    Identification of CUL3-KLHL3 as the E3 ligase for WNK kinases, with disease mutations disrupting adaptor-substrate or adaptor-CUL3 interactions, provided a direct molecular explanation for familial hyperkalemic hypertension (Gordon syndrome).

    Evidence In vitro reconstituted ubiquitination of WNK, mapping of 13/15 dominant KLHL3 mutations to interaction surfaces, disease mutant analysis

    PMID:23387299

    Open questions at the time
    • Whether WNK1 and WNK4 are differentially regulated by KLHL3 not resolved
    • Tissue-specific regulation of KLHL3-CUL3 activity in kidney not defined
  11. 2014 High

    Discovery that CUL3-KLHL20 catalyzes K33-linked non-degradative polyubiquitination of coronin 7 for TGN targeting demonstrated that CRL3 outputs extend beyond proteasomal degradation to include ubiquitin-dependent protein trafficking.

    Evidence In vivo ubiquitination with chain-specific antibodies, localization studies, and post-Golgi trafficking readouts

    PMID:24768539

    Open questions at the time
    • Structural basis for chain-type selectivity by CRL3-KLHL20 unknown
    • Generality of K33-linked ubiquitination among CRL3 complexes not assessed
  12. 2015 High

    Identification of CUL3-KLHL20 as the E3 ligase terminating autophagy by degrading ULK1 and other autophagy regulators, and of CUL3-KBTBD6/7 recruiting GABARAP to degrade TIAM1 for RAC1 signaling restriction, expanded CRL3 into autophagy regulation and spatial signaling control.

    Evidence In vivo ubiquitination, KLHL20 knockout with autophagy flux readouts and mouse models; KBTBD6/7-GABARAP binding and TIAM1 degradation assays

    PMID:25684205 PMID:26687681

    Open questions at the time
    • How ULK1 autophosphorylation creates KLHL20 degron not structurally defined
    • Physiological contexts where GABARAP-directed CRL3 activity is critical remain limited
  13. 2019 Medium

    Showing that CUL3 haploinsufficiency in neurons increases eIF4G1-dependent translation and causes ASD-like behaviors linked CUL3 to neurodevelopmental disease through translational control, and demonstrated pharmacological rescue.

    Evidence Conditional Cul3 knockout mouse with electrophysiology, behavioral assays, and pharmacological rescue of eIF4G1-dependent translation

    PMID:31780330

    Open questions at the time
    • Specific BTB adaptor for eIF4G1 not identified
    • Whether CUL3 directly ubiquitinates eIF4G1 not shown by in vitro reconstitution
    • Mechanism by which enhanced translation drives excitatory/inhibitory imbalance not resolved
  14. 2021 Medium

    Multiple studies expanded CUL3 substrates to include ACLY (metabolic reprogramming in Tregs), PD-L1 (immune checkpoint regulation), Plastin3 (neuronal migration), and Beclin-1 (autophagy), reinforcing CUL3 as a hub E3 ligase coordinating metabolism, immunity, and development.

    Evidence Co-immunoprecipitation and ubiquitination assays with functional readouts across T-cell differentiation, tumor immune escape, cortical lamination, and autophagy

    PMID:33977871 PMID:34031387 PMID:34491895 PMID:36198437

    Open questions at the time
    • Many new substrate-adaptor pairs identified in single labs await independent replication
    • In vitro reconstitution of ubiquitination lacking for several substrates
    • Crosstalk between different CRL3 complexes competing for CUL3 scaffold not systematically studied
  15. 2023 High

    The crystal structure of human KEAP1 BTB-3box bound to CUL3 NTD at atomic resolution established the 2:2 heterotetrameric assembly and showed how pharmacological agents (CDDO) modulate but do not fully disrupt this interface.

    Evidence X-ray crystallography of human KEAP1-CUL3 complex with TR-FRET binding assay and pharmacological profiling

    PMID:37156295

    Open questions at the time
    • Full-length neddylated CRL3 holo-complex structure still unavailable
    • How CDDO partial disruption translates to in vivo NRF2 activation not quantitatively modeled

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the cell balances competition among >80 BTB adaptors for a shared CUL3 scaffold, whether adaptor exchange is regulated, and how CRL3 activity is coordinated across subcellular compartments remain major unresolved questions.
  • No systematic quantification of BTB adaptor abundance relative to CUL3 pool
  • No full-length neddylated CRL3 cryo-EM structure with E2~Ub conjugate
  • Mechanism of adaptor exchange on CUL3 scaffold not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 13 GO:0016874 ligase activity 5
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2 GO:0005886 plasma membrane 1
Pathway
R-HSA-392499 Metabolism of proteins 10 R-HSA-8953897 Cellular responses to stimuli 4 R-HSA-162582 Signal Transduction 3 R-HSA-9612973 Autophagy 2 R-HSA-5653656 Vesicle-mediated transport 1
Partners
KEAP1KLHL13KLHL20KLHL21KLHL3KLHL9RBX1SPOP
Complex memberships
CRL3 (CUL3-RBX1-BTB adaptor E3 ligase)CUL3-KEAP1-RBX1CUL3-KLHL3CUL3-SPOP

Evidence

Reading pass · 48 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 Keap1 functions as a substrate adaptor protein for a Cul3-dependent E3 ubiquitin ligase complex; Keap1 assembles with Cul3 and Rbx1 to target multiple lysine residues in the Neh2 domain of Nrf2 for ubiquitin conjugation both in vitro and in vivo. Oxidative stress and sulforaphane inhibit Keap1-dependent ubiquitination of Nrf2 by decreasing Keap1-Cul3 association, with Cys151 of Keap1 being critical for this regulatory dissociation. In vitro ubiquitination assay, co-immunoprecipitation, site-directed mutagenesis (Keap1 Cys151Ser) Molecular and cellular biology High 15367669 15572695
2004 Keap1 acts as an adaptor bridging Nrf2 to Cul3, forming a cytoplasmic E3 ligase complex that polyubiquitinates Nrf2. Inhibition of either Keap1 or Cul3 increases Nrf2 nuclear accumulation, demonstrating that Keap1 restrains Nrf2 via targeting it to the Cul3-based E3 ligase. In vitro and in vivo polyubiquitination assays, siRNA knockdown with nuclear localization readout Molecular and cellular biology High 15367669
2003 BTB-domain proteins function as substrate-specific adaptors for CUL-3 in an SCF-like E3 ubiquitin ligase, merging the functional properties of Skp1 and F-box proteins into a single polypeptide. The BTB protein MEL-26 directly bridges CUL-3 to the substrate MEI-1/katanin in C. elegans. Biochemical reconstitution, genetic epistasis, co-immunoprecipitation, two-hybrid screen Nature High 13679921 13679922
2003 Neddylation (Nedd8 conjugation) of CUL-3 is required for its E3 ligase activity toward MEI-1/Katanin in C. elegans; conversely, deneddylation by the COP9 signalosome is also required, indicating that cycles of CUL-3 neddylation/deneddylation are necessary for ligase activity in vivo. RNAi-based epistasis, biochemical fractionation, in vivo neddylation assays Current biology High 12781129
2009 SPOP (a MATH-BTB protein) recruits substrates via a defined SPOP-binding consensus (SBC) to a dimeric Cul3-SPOP assembly. A conserved helical structure C-terminal of BTB domains (the '3-box') facilitates Cul3 binding analogously to F-box/SOCS-box motifs in other cullin E3s; SPOP dimerization and conformational flexibility enable avid engagement of multiple SBCs within substrates. Crystal structure determination, SAXS, biochemical binding assays, mutagenesis Molecular cell High 19818708
2013 Crystal structures of KLHL11 BTB-BACK domains in complex with the Cul3 N-terminal domain reveal that Cul3 interaction depends on a unique N-terminal extension sequence of the BTB protein that packs against the 3-box in a hydrophobic groove between BTB and BACK domains; deletion of this N-terminal region causes a 30-fold loss in Cul3 binding affinity. X-ray crystallography, biophysical binding assays (ITC/SPR), deletion mutagenesis The Journal of biological chemistry High 23349464
2007 A Cul3-based E3 ligase in complex with BTB-Kelch adaptors KLHL9 and KLHL13 ubiquitylates Aurora B, removing it from mitotic chromosomes and allowing its accumulation on the central spindle during anaphase, which is required for correct chromosome alignment, midzone/midbody formation, and cytokinesis completion. Co-immunoprecipitation, in vitro reconstituted ubiquitination assay, RNAi knockdown with mitotic phenotype readout Developmental cell High 17543862
2009 The Cul3-KLHL21 E3 ubiquitin ligase directly binds Aurora B through KLHL21, mediates Aurora B ubiquitination in vitro, and regulates translocation of the chromosomal passenger complex from chromosomes to the spindle midzone in anaphase, which is required for cytokinesis; KLHL21 localizes to midzone microtubules in anaphase and recruits Aurora B and Cul3 to this region. Co-immunoprecipitation, in vitro ubiquitination assay, siRNA knockdown with cytokinesis and CPC localization readout The Journal of cell biology High 19995937
2015 Cul3-KLHL20 ubiquitin ligase promotes proteasomal degradation of ULK1 (following ULK1 autophosphorylation-mediated KLHL20 recruitment) and also controls turnover of ATG13, VPS34, Beclin-1, and ATG14, thereby terminating autophagy. Impairment of this regulation potentiates starvation-induced cell death and exacerbates diabetes-associated muscle atrophy. Co-immunoprecipitation, in vivo ubiquitination assay, KLHL20 knockdown/knockout with autophagy flux readouts, mouse models Molecular cell High 26687681
2013 The CUL3-KLHL3 E3 ligase complex ubiquitylates WNK kinase isoforms in vitro and controls their protein levels in cells; disease-causing mutations in KLHL3 (13/15 dominant mutations) or WNK4 (Gordon's syndrome mutations) disrupt the KLHL3-WNK or KLHL3-Cul3 interactions respectively, explaining the pathological accumulation of WNK kinases in familial hyperkalemic hypertension. Immunoprecipitation, in vitro ubiquitination with recombinant complex, siRNA knockdown, site-directed mutagenesis The Biochemical journal High 23387299
2014 Cul3-KLHL20 E3 ligase catalyzes K33-linked (non-degradative) polyubiquitination on coronin 7 (Crn7), facilitating Crn7 targeting to the trans-Golgi network (TGN) through a ubiquitin-dependent interaction with Eps15, promoting TGN-pool F-actin assembly and post-Golgi trafficking. In vivo ubiquitination assays with chain-specific analysis, localization studies, dominant-negative constructs, siRNA knockdown Molecular cell High 24768539
2005 Neddylation of Cul3 renders it unstable, while COP9 signalosome (CSN) deneddylation recycles neddylated, unstable cullins into stable, unneddylated forms; in cells deficient for CSN isopeptidase activity, Cul3 protein is unstable, demonstrating that CSN deneddylation is required to maintain normal Cul3 protein levels. Genetic loss-of-function (CSN mutants), immunoblot for neddylation status and protein stability, unneddylatable mutant analysis Nature cell biology High 16127432
2008 Covalent modification of Keap1 Cys151 by the model electrophile IAB causes progressive loss of Keap1 secondary structure and dissociation from Cul3 in vitro; in cells, Cys151 is one of the most reactive residues and is required for IAB-mediated dissociation of the Keap1-Cul3 interaction, establishing Cys151 as the critical alkylation sensor. CD spectroscopy, in vitro binding assay with recombinant proteins, quantitative mass spectrometry-based kinetic adduction analysis, site-directed mutagenesis Chemical research in toxicology High 18251510
2006 SPOP functions as a BTB adaptor for Cul3-based ubiquitin ligase to ubiquitinate and degrade Daxx, regulating Daxx-mediated transcriptional repression and apoptosis. Co-immunoprecipitation, ubiquitination assay, shRNA knockdown, functional transcription assays, apoptosis assays The Journal of biological chemistry High 16524876
2009 The MATH-BTB protein HIB/SPOP recognizes multiple Ser/Thr-rich degron motifs in Ci/Gli that bind cooperatively; both HIB/SPOP and Ci form dimers/oligomers and engage in multivalent interactions, underlying cooperative in vivo degradation by the Cul3-HIB/SPOP E3 ligase. Binding assays, mutagenesis, genetic epistasis in Drosophila, in vivo ubiquitination Proceedings of the National Academy of Sciences of the United States of America High 19955409
2007 Cul3 is required for constitutive turnover of cyclin E; biallelic loss of Cul3 in primary fibroblasts causes increased cyclin E expression and reduced cell viability, while Cul3 deletion in mouse liver causes dramatic increases in cyclin E levels, cell size, and ploidy, establishing Cul3-mediated cyclin E degradation as essential for maintaining cellular quiescence. Conditional Cul3 knockout mouse, cyclin E immunoblot, cell cycle analysis, liver histology Molecular and cellular biology High 17339333
2004 RhoBTB2 binds to the Cul3 ubiquitin ligase scaffold via its first BTB domain and is a substrate of the Cul3-based ubiquitin ligase complex both in vitro and in vivo; a cancer-associated missense mutant of RhoBTB2 fails to bind Cul3 and escapes ubiquitin/proteasome-mediated regulation, resulting in increased protein levels. Co-immunoprecipitation, in vitro and in vivo ubiquitination assays, mutagenesis Genes & development High 15107402
2009 The human DCNL3 protein (a Dcn1-like protein) promotes Cul3 neddylation at the plasma membrane; DCNL3 accumulates at the plasma membrane through a lipid-modified N-terminal motif, recruits Cul3 to membranes, and is functionally important for Cul3 neddylation in vivo. RNAi knockdown with neddylation readout, subcellular fractionation/localization, yeast complementation, dominant-negative Cul3 mutant Proceedings of the National Academy of Sciences of the United States of America High 19617556
2006 Actinfilin, a BTB-Kelch protein, acts as a Cul3 substrate adaptor linking the kainate receptor subunit GluR6 to the Cul3 E3 ubiquitin ligase complex via the Kelch repeat domain, promoting GluR6 ubiquitination and degradation; Cul3-deficient neurons show elevated synaptic GluR6 levels. Co-immunoprecipitation, ubiquitination assay, domain mapping, RNAi, dominant-negative Cul3 in hippocampal neurons The Journal of biological chemistry High 17062563
2006 The BTB-Kelch protein KEL-8 is a substrate receptor for CUL-3-dependent ubiquitin ligase that is required for ubiquitin-mediated turnover of the AMPA-type glutamate receptor subunit GLR-1 at postsynaptic clusters in C. elegans neurons. Genetic screen, co-immunoprecipitation, in vivo ubiquitination, behavioral assays Molecular biology of the cell High 16394099
2015 CUL3-KBTBD6/KBTBD7 ubiquitin ligase complex ubiquitylates and promotes proteasomal degradation of TIAM1 (a RAC1-specific GEF), spatially restricting RAC1 signaling; KBTBD6 and KBTBD7 use ATG8 family-interacting motifs to bind GABARAP proteins, and TIAM1 degradation by this complex depends on GABARAP binding, linking membrane-localized GABARAP scaffolds to Cul3 activity. Co-immunoprecipitation, in vivo ubiquitination, siRNA knockdown with RAC1 activity and actin morphology readouts, proximity ligation assay Molecular cell High 25684205
2009 Prothymosin-alpha mediates nuclear import of the INrf2(Keap1)/Cul3/Rbx1 complex; once inside the nucleus, the complex exchanges prothymosin-alpha for Nrf2, resulting in nuclear Nrf2 ubiquitination and degradation, providing a mechanism to rapidly switch off Nrf2-dependent gene expression. Co-immunoprecipitation, subcellular fractionation, nuclear import assays, siRNA knockdown The Journal of biological chemistry Medium 19279002
2008 PIPKIIbeta and SPOP interact and co-localize at nuclear speckles; SPOP mediates ubiquitylation of PIPKIIbeta by Cul3. Stimulation of the p38 MAPK pathway enhances Cul3-SPOP ubiquitin ligase activity toward multiple substrates; a kinase-dead PIPKIIbeta mutant that increases phosphatidylinositol 5-phosphate levels similarly stimulates Cul3-SPOP activity through p38-dependent signaling. Yeast two-hybrid, co-immunoprecipitation, ubiquitination assay, p38 pathway pharmacological inhibition The Journal of biological chemistry Medium 18218622
2009 The Cul3-KLHL18 E3 ligase ubiquitylates Aurora-A, and depletion of Cul3 or KLHL18 causes a delay in mitotic entry with delayed centrosomal activation of Aurora-A; the CUL3-KLHL18-ROC1 complex ubiquitylates Aurora-A in vitro. Co-immunoprecipitation, in vitro ubiquitination assay, siRNA knockdown with mitotic entry timing readout Biology open Medium 23213400
2019 Cul3-Klhl18 ubiquitin ligase promotes ubiquitination and degradation of Unc119, a rod transducin α-subunit (Tα)-interacting protein; Klhl18 preferentially recognizes casein kinase 2-phosphorylated Unc119, which is dephosphorylated by Ca2+-dependent calcineurin, linking Ca2+ signaling to Cul3-Klhl18 activity and modulating rod Tα translocation during light/dark adaptation. Klhl18 knockout mouse, in vivo ubiquitination assay, co-immunoprecipitation, calcineurin inhibitor treatment, photoreceptor localization studies The EMBO journal High 31696965
2009 Modification of Keap1 Cys151 to bulkier amino acids (e.g., Trp) decreases Keap1 affinity for Cul3, abolishes Cul3-mediated Nrf2 ubiquitination, and activates ARE-driven gene expression; a systematic mutagenesis series shows that the extent of ARE activation correlates with the partial molar volume of the residue at position 151, suggesting steric clashes disrupt the Keap1-Cul3 interaction. In vitro ubiquitination assay, site-directed mutagenesis (12-residue series), ARE reporter assay, Cul3 binding assay The Biochemical journal High 19489739
2005 Keap1 itself is ubiquitinated by the Cul3-dependent complex; oxidative stress increases Keap1 ubiquitination and decreases Keap1 steady-state levels through a proteasome-independent (non-26S) degradation pathway, representing a regulatory switch from substrate to substrate adaptor ubiquitination. In vivo ubiquitination assay, proteasome inhibitor treatment, pulse-chase stability assay The Journal of biological chemistry Medium 15983046
2017 p97 segregase, with cofactors UFD1/NPL4 and UBXN7, extracts ubiquitylated NRF2 from the KEAP1-CUL3 E3 complex for efficient delivery to the proteasome; this establishes p97 as an essential component downstream of CUL3-mediated NRF2 ubiquitination in the canonical degradation pathway. Co-immunoprecipitation, siRNA knockdown, pharmacological p97 inhibition, immunofluorescence Molecular and cellular biology Medium 28115426
2009 KLHL7 forms a dimer, assembles with Cul3 through its BTB and BACK domains, and mediates K48-linked polyubiquitination for proteasomal degradation; a retinitis pigmentosa-causing missense mutation in the BACK domain selectively impairs Cul3 interaction without affecting dimerization, and when incorporated as a heterodimer reduces overall E3 ligase activity in a dominant-negative manner. Co-immunoprecipitation, in vivo ubiquitination assay, dimerization assays, domain mapping, mutagenesis The Journal of biological chemistry Medium 21828050
2008 BTB protein KLHL12 binds the polymorphic third intracellular loop of the dopamine D4 receptor through its Kelch domain and also interacts with Cullin3, functioning as an adaptor to target the D4 receptor to a Cul3-based E3 ubiquitin ligase complex for ubiquitination. Co-immunoprecipitation, ubiquitination assay, domain mapping The Journal of biological chemistry Medium 18303015
2009 The Cul3/KLHDC5 (Ctb9) E3 ligase complex ubiquitinates and degrades the microtubule-severing protein p60/katanin in mammalian cells; cells deficient for Cul3 or KLHDC5 show increased p60/katanin levels, microtubule density abnormalities, and mitotic defects including persistent microtubule bridges. Two-hybrid screen, co-immunoprecipitation, in vivo ubiquitination assay, overexpression and knockdown with microtubule phenotype readout The Journal of biological chemistry Medium 19261606
2011 BRMS1 (breast cancer metastasis suppressor 1) is ubiquitinated and destabilized by the Cul3-SPOP E3 ubiquitin ligase complex, with SPOP serving as the adaptor protein; SPOP knockdown increases BRMS1 protein levels and represses expression of BRMS1 target genes. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, target gene expression analysis Biochemical and biophysical research communications Medium 22085717
2009 HSF2 PEST sequences interact directly with Cul3, recruiting HSF2 to the Cul3-RING E3 ubiquitin ligase for ubiquitination and degradation; this identifies PEST-sequence-mediated direct interaction with Cul3 (rather than via a BTB adaptor) as a mechanism for substrate recruitment. Co-immunoprecipitation, in vivo ubiquitination assay, domain mapping Cell stress & chaperones Medium 19768582
2014 In Drosophila, the CUL3/RDX E3 ligase ubiquitylates CENP-A in a CAL1-dependent manner; however, this ubiquitylation does not trigger CENP-A degradation but instead stabilizes CENP-A and CAL1 at centromeres; loss of RDX leads to rapid degradation of CENP-A and CAL1 and chromosome segregation defects. Co-immunoprecipitation, in vivo ubiquitination assay, RNAi knockdown with centromere localization and chromosome segregation readouts Developmental cell Medium 24636256
2019 CUL3 interacts with eIF4G1, a cap-dependent translation initiation factor; CUL3 deficiency in neurons leads to accumulation of eIF4G1 and enhanced cap-dependent translation, glutamatergic transmission, and neuronal excitability causing ASD-like behaviors. Pharmacological inhibition of eIF4G1 function rescues these deficits. Proteomic analysis, co-immunoprecipitation, conditional Cul3 knockout mouse, electrophysiology, behavioral assays, pharmacological rescue Neuron Medium 31780330
2021 CUL3 interacts with BECN1 (Beclin1) via the adaptor KLHL38 and promotes K48-linked polyubiquitination and proteasomal degradation of BECN1, thereby inhibiting autophagy. Co-immunoprecipitation, ubiquitination assay with linkage-specific analysis, CHX chase, siRNA knockdown Autophagy Medium 33977871
2021 CUL3 controls neuronal migration and cortical lamination by tightly regulating the amount of Plastin3 (Pls3), an actin-bundling protein; Pls3 levels are inversely proportional to neural migration speed and cell-autonomously regulate actin cytoskeleton organization and cell migration. Conditional Cul3 haploinsufficiency mouse model, cortical lamination analysis, proteomic identification of Pls3, rescue experiments Nature communications Medium 34031387
2021 CUL3-KLHL25 E3 ligase ubiquitinates and degrades ACLY (ATP-citrate lyase) during iTreg differentiation, reducing malonyl-CoA levels and thereby relieving inhibition of CPT1 to facilitate a metabolic shift from fatty acid synthesis to fatty acid oxidation. Co-immunoprecipitation, in vivo ubiquitination assay, metabolite measurements, siRNA knockdown with T-cell differentiation readout eLife Medium 34491895
2019 KLHL9 and KLHL13 form a Cul3-based E3 ligase complex that ubiquitinates and promotes proteasomal degradation of IRS1, causing insulin resistance when autophagy (ATG16L1) is deficient; knockdown of KLHL9, KLHL13, or Cul3 restores IRS1 expression and insulin signaling. BioID proximity proteomics, co-immunoprecipitation, proteasome inhibitor treatment, siRNA knockdown with insulin signaling readout The Journal of biological chemistry Medium 31515271
2001 ROC1-CUL3 immunocomplexes promote polyubiquitination of cyclin D1 in vitro; RING finger mutations in ROC1 eliminate E3 ligase activity toward cyclin D1, and ubiquitination is accompanied by autoubiquitination of Cul3. In vitro ubiquitination assay, immunoprecipitation, RING finger mutagenesis FEBS letters Medium 11311237
2023 Crystal structure of human KEAP1 BTB-3box domains in complex with CUL3 N-terminal domain shows a 2:2 heterotetrameric assembly; the CUL3 N-terminal extension contributes significantly to high-affinity binding; the drug CDDO reduces but does not fully disrupt KEAP1-CUL3 interaction. X-ray crystallography, TR-FRET-based binding assay, pharmacological profiling Free radical biology & medicine High 37156295
2017 In Drosophila, GCL (Germ cell-less), a conserved BTB protein, acts as a substrate-specific adaptor for CUL3-RING ubiquitin ligase (CRL3GCL) to mediate ubiquitination and degradation of Torso (a receptor tyrosine kinase), promoting germline fate; GCL nuclear envelope release during mitosis provides cell-cycle-dependent spatiotemporal specificity for RTK degradation. Genetic epistasis, co-immunoprecipitation, in vivo ubiquitination assay, live imaging for localization Developmental cell Medium 28743001
2021 CUL3 loss-of-function variants reduce CUL3 protein stability and impair ubiquitin-protein conjugation; specifically, EIF4EBP1 (4E-BP1) fails to be targeted for proteasomal degradation in patient-derived cells with CUL3 loss-of-function variants, identifying 4E-BP1 as a CUL3 substrate. Patient-derived T-cell assays, ubiquitin conjugate measurement, 4E-BP1 stability assay Annals of neurology Medium 39301775
2012 Antioxidant-induced phosphorylation of INrf2 (Keap1) Tyr85 controls nuclear export of the INrf2-Cul3-Rbx1 complex; mutation of Tyr85 blocks nuclear export of INrf2 and co-exported Cul3-Rbx1, leading to nuclear accumulation of Nrf2 during the post-induction period. Site-directed mutagenesis, subcellular fractionation, co-immunoprecipitation, siRNA knockdown Journal of cell science Medium 22448038
2021 CUL3/SPOP complex promotes ubiquitination and proteasomal degradation of PD-L1 protein; overexpression of CUL3 reduces PD-L1 levels and suppresses immune escape of ovarian cancer cells in vitro and in vivo. Co-immunoprecipitation, in vivo ubiquitination assay, gain/loss-of-function with PD-L1 protein readout, xenograft mouse model Journal for immunotherapy of cancer Medium 36198437
2021 G3BP1 acts as a competitive inhibitor of the Cul3-SPOP E3 ubiquitin ligase by directly binding SPOP, preventing Cul3SPOP from ubiquitinating its substrates including AR pathway components, thereby promoting prostate cancer progression. Co-immunoprecipitation, ubiquitination assay, transcriptomic and functional studies Nature communications Medium 34795264
2021 Novel CUL3 variant (Δ474-477) causes increased CUL3 autoubiquitination and autodegradation, and the remaining CUL3Δ474-477 shows enhanced NEDD8 modification and increased CUL3-KLHL3 complex formation that is impaired in ubiquitinating WNK4, explaining familial hyperkalemic hypertension pathophysiology. Patient-derived cells, in vitro ubiquitination assay, proteomic CUL3 complex analysis, neddylation assays Hypertension Medium 34878901
2020 CUL3 directly binds and ubiquitinates β-catenin, promoting its degradation; miR-23a-3p suppresses CUL3 expression, thereby reducing β-catenin ubiquitination and increasing its stability during embryo implantation. Co-immunoprecipitation, ubiquitination assay, luciferase reporter, siRNA knockdown Journal of molecular endocrinology Low 32716006

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex. Molecular and cellular biology 1048 15572695
2004 The Keap1-BTB protein is an adaptor that bridges Nrf2 to a Cul3-based E3 ligase: oxidative stress sensing by a Cul3-Keap1 ligase. Molecular and cellular biology 839 15367669
2008 Cancer related mutations in NRF2 impair its recognition by Keap1-Cul3 E3 ligase and promote malignancy. Proceedings of the National Academy of Sciences of the United States of America 627 18757741
2003 BTB proteins are substrate-specific adaptors in an SCF-like modular ubiquitin ligase containing CUL-3. Nature 418 13679922
2009 Structures of SPOP-substrate complexes: insights into molecular architectures of BTB-Cul3 ubiquitin ligases. Molecular cell 410 19818708
2003 The BTB protein MEL-26 is a substrate-specific adaptor of the CUL-3 ubiquitin-ligase. Nature 359 13679921
2005 Ubiquitination of Keap1, a BTB-Kelch substrate adaptor protein for Cul3, targets Keap1 for degradation by a proteasome-independent pathway. The Journal of biological chemistry 256 15983046
2013 Structural basis for Cul3 protein assembly with the BTB-Kelch family of E3 ubiquitin ligases. The Journal of biological chemistry 227 23349464
2007 A Cul3-based E3 ligase removes Aurora B from mitotic chromosomes, regulating mitotic progression and completion of cytokinesis in human cells. Developmental cell 196 17543862
2015 Cul3-KLHL20 Ubiquitin Ligase Governs the Turnover of ULK1 and VPS34 Complexes to Control Autophagy Termination. Molecular cell 186 26687681
2013 The CUL3-KLHL3 E3 ligase complex mutated in Gordon's hypertension syndrome interacts with and ubiquitylates WNK isoforms: disease-causing mutations in KLHL3 and WNK4 disrupt interaction. The Biochemical journal 180 23387299
2006 BTB domain-containing speckle-type POZ protein (SPOP) serves as an adaptor of Daxx for ubiquitination by Cul3-based ubiquitin ligase. The Journal of biological chemistry 173 16524876
2008 Covalent modification at Cys151 dissociates the electrophile sensor Keap1 from the ubiquitin ligase CUL3. Chemical research in toxicology 172 18251510
2021 CUL3 (cullin 3)-mediated ubiquitination and degradation of BECN1 (beclin 1) inhibit autophagy and promote tumor progression. Autophagy 169 33977871
2002 Distinct protein degradation mechanisms mediated by Cul1 and Cul3 controlling Ci stability in Drosophila eye development. Genes & development 163 12231629
2003 Neddylation and deneddylation of CUL-3 is required to target MEI-1/Katanin for degradation at the meiosis-to-mitosis transition in C. elegans. Current biology : CB 149 12781129
2005 Neddylation and deneddylation regulate Cul1 and Cul3 protein accumulation. Nature cell biology 147 16127432
2009 Cul3-mediated Nrf2 ubiquitination and antioxidant response element (ARE) activation are dependent on the partial molar volume at position 151 of Keap1. The Biochemical journal 144 19489739
2006 Arsenic induces NAD(P)H-quinone oxidoreductase I by disrupting the Nrf2 x Keap1 x Cul3 complex and recruiting Nrf2 x Maf to the antioxidant response element enhancer. The Journal of biological chemistry 143 16785233
2014 K33-Linked Polyubiquitination of Coronin 7 by Cul3-KLHL20 Ubiquitin E3 Ligase Regulates Protein Trafficking. Molecular cell 134 24768539
2013 CUL3 and NRF2 mutations confer an NRF2 activation phenotype in a sporadic form of papillary renal cell carcinoma. Cancer research 132 23365135
2009 Multiple Ser/Thr-rich degrons mediate the degradation of Ci/Gli by the Cul3-HIB/SPOP E3 ubiquitin ligase. Proceedings of the National Academy of Sciences of the United States of America 130 19955409
2009 Cysteine-based regulation of the CUL3 adaptor protein Keap1. Toxicology and applied pharmacology 126 19560482
2015 Spatiotemporal 16p11.2 protein network implicates cortical late mid-fetal brain development and KCTD13-Cul3-RhoA pathway in psychiatric diseases. Neuron 121 25695269
2009 The Cul3-KLHL21 E3 ubiquitin ligase targets aurora B to midzone microtubules in anaphase and is required for cytokinesis. The Journal of cell biology 118 19995937
2011 Modulation of phototropic responsiveness in Arabidopsis through ubiquitination of phototropin 1 by the CUL3-Ring E3 ubiquitin ligase CRL3(NPH3). The Plant cell 117 21990941
2008 Activation of Nrf2 by arsenite and monomethylarsonous acid is independent of Keap1-C151: enhanced Keap1-Cul3 interaction. Toxicology and applied pharmacology 114 18417180
2004 RhoBTB2 is a substrate of the mammalian Cul3 ubiquitin ligase complex. Genes & development 106 15107402
2016 Absolute Amounts and Status of the Nrf2-Keap1-Cul3 Complex within Cells. Molecular and cellular biology 100 27697860
2019 CUL3 Deficiency Causes Social Deficits and Anxiety-like Behaviors by Impairing Excitation-Inhibition Balance through the Promotion of Cap-Dependent Translation. Neuron 95 31780330
2017 p97 Negatively Regulates NRF2 by Extracting Ubiquitylated NRF2 from the KEAP1-CUL3 E3 Complex. Molecular and cellular biology 93 28115426
2017 BPM-CUL3 E3 ligase modulates thermotolerance by facilitating negative regulatory domain-mediated degradation of DREB2A in Arabidopsis. Proceedings of the National Academy of Sciences of the United States of America 86 28923951
2012 Cul3 and the BTB adaptor insomniac are key regulators of sleep homeostasis and a dopamine arousal pathway in Drosophila. PLoS genetics 86 23055946
2020 CUL3BPM E3 ubiquitin ligases regulate MYC2, MYC3, and MYC4 stability and JA responses. Proceedings of the National Academy of Sciences of the United States of America 84 32123086
2009 Cul3 overexpression depletes Nrf2 in breast cancer and is associated with sensitivity to carcinogens, to oxidative stress, and to chemotherapy. Molecular cancer therapeutics 83 19638449
2009 The human Dcn1-like protein DCNL3 promotes Cul3 neddylation at membranes. Proceedings of the National Academy of Sciences of the United States of America 77 19617556
2008 Characterization of RhoBTB-dependent Cul3 ubiquitin ligase complexes--evidence for an autoregulatory mechanism. Experimental cell research 73 18835386
2006 KEL-8 is a substrate receptor for CUL3-dependent ubiquitin ligase that regulates synaptic glutamate receptor turnover. Molecular biology of the cell 71 16394099
2006 Actinfilin is a Cul3 substrate adaptor, linking GluR6 kainate receptor subunits to the ubiquitin-proteasome pathway. The Journal of biological chemistry 71 17062563
2015 CUL3-KBTBD6/KBTBD7 ubiquitin ligase cooperates with GABARAP proteins to spatially restrict TIAM1-RAC1 signaling. Molecular cell 70 25684205
2007 ELA1 and CUL3 are required along with ELC1 for RNA polymerase II polyubiquitylation and degradation in DNA-damaged yeast cells. Molecular and cellular biology 68 17296727
2021 CUL3 E3 ligases in plant development and environmental response. Nature plants 67 33452490
2008 Coordinated activation of the nuclear ubiquitin ligase Cul3-SPOP by the generation of phosphatidylinositol 5-phosphate. The Journal of biological chemistry 67 18218622
2020 Hippuric Acid Promotes Renal Fibrosis by Disrupting Redox Homeostasis via Facilitation of NRF2-KEAP1-CUL3 Interactions in Chronic Kidney Disease. Antioxidants (Basel, Switzerland) 66 32854194
2008 BTB Protein KLHL12 targets the dopamine D4 receptor for ubiquitination by a Cul3-based E3 ligase. The Journal of biological chemistry 65 18303015
2010 An autoregulatory loop between Nrf2 and Cul3-Rbx1 controls their cellular abundance. The Journal of biological chemistry 59 20452971
2019 Behavioral, circuitry, and molecular aberrations by region-specific deficiency of the high-risk autism gene Cul3. Molecular psychiatry 56 31455858
2019 The miR-15a-5p-XIST-CUL3 regulatory axis is important for sepsis-induced acute kidney injury. Renal failure 56 31658856
2009 Prothymosin-alpha mediates nuclear import of the INrf2/Cul3 Rbx1 complex to degrade nuclear Nrf2. The Journal of biological chemistry 55 19279002
2007 Constitutive turnover of cyclin E by Cul3 maintains quiescence. Molecular and cellular biology 53 17339333
2013 Frequent concerted genetic mechanisms disrupt multiple components of the NRF2 inhibitor KEAP1/CUL3/RBX1 E3-ubiquitin ligase complex in thyroid cancer. Molecular cancer 52 24138990
2020 CRL3s: The BTB-CUL3-RING E3 Ubiquitin Ligases. Advances in experimental medicine and biology 50 31898230
2011 Ubiquitin ligase activity of Cul3-KLHL7 protein is attenuated by autosomal dominant retinitis pigmentosa causative mutation. The Journal of biological chemistry 50 21828050
2019 Impact of KEAP1/NFE2L2/CUL3 mutations on duration of response to EGFR tyrosine kinase inhibitors in EGFR mutated non-small cell lung cancer. Lung cancer (Amsterdam, Netherlands) 49 31319993
2011 Genetic disruption of KEAP1/CUL3 E3 ubiquitin ligase complex components is a key mechanism of NF-kappaB pathway activation in lung cancer. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 49 21795997
2011 Breast cancer metastasis suppressor 1 (BRMS1) is destabilized by the Cul3-SPOP E3 ubiquitin ligase complex. Biochemical and biophysical research communications 49 22085717
2009 The Cul3/Klhdc5 E3 ligase regulates p60/katanin and is required for normal mitosis in mammalian cells. The Journal of biological chemistry 46 19261606
2019 Cul3 and insomniac are required for rapid ubiquitination of postsynaptic targets and retrograde homeostatic signaling. Nature communications 45 31278365
2004 Protein degradation: CUL-3 and BTB--partners in proteolysis. Current biology : CB 43 14738749
2015 Transposon Mutagenesis Screen Identifies Potential Lung Cancer Drivers and CUL3 as a Tumor Suppressor. Molecular cancer research : MCR 41 25995385
2014 Detection of mutations in KLHL3 and CUL3 in families with FHHt (familial hyperkalaemic hypertension or Gordon's syndrome). Clinical science (London, England : 1979) 41 24266877
2013 Aberrant reduction of MiR-141 increased CD47/CUL3 in Hirschsprung's disease. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 40 24334875
2021 Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. Nature communications 37 34031387
2017 GCL and CUL3 Control the Switch between Cell Lineages by Mediating Localized Degradation of an RTK. Developmental cell 37 28743001
2021 Pyrroloquinoline quinone (PQQ) alleviated sepsis-induced acute liver injury, inflammation, oxidative stress and cell apoptosis by downregulating CUL3 expression. Bioengineered 36 34227919
2014 The E3 ligase CUL3/RDX controls centromere maintenance by ubiquitylating and stabilizing CENP-A in a CAL1-dependent manner. Developmental cell 36 24636256
2012 Antioxidant-induced INrf2 (Keap1) tyrosine 85 phosphorylation controls the nuclear export and degradation of the INrf2-Cul3-Rbx1 complex to allow normal Nrf2 activation and repression. Journal of cell science 36 22448038
2005 Requirement of Cul3 for axonal arborization and dendritic elaboration in Drosophila mushroom body neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 35 15843622
2020 De novo variants in CUL3 are associated with global developmental delays with or without infantile spasms. Journal of human genetics 34 32341456
2019 Deficiency of the autophagy gene ATG16L1 induces insulin resistance through KLHL9/KLHL13/CUL3-mediated IRS1 degradation. The Journal of biological chemistry 34 31515271
2021 Tangeretin maintains antioxidant activity by reducing CUL3 mediated NRF2 ubiquitination. Food chemistry 33 34237577
2021 ACLY ubiquitination by CUL3-KLHL25 induces the reprogramming of fatty acid metabolism to facilitate iTreg differentiation. eLife 31 34491895
2021 G3BP1 inhibits Cul3SPOP to amplify AR signaling and promote prostate cancer. Nature communications 31 34795264
2019 Cul3-Klhl18 ubiquitin ligase modulates rod transducin translocation during light-dark adaptation. The EMBO journal 31 31696965
2011 The CUL3-KLHL18 ligase regulates mitotic entry and ubiquitylates Aurora-A. Biology open 31 23213400
2019 Disruption of CUL3-mediated ubiquitination causes proximal tubule injury and kidney fibrosis. Scientific reports 28 30872636
2017 Cul3 neddylation is crucial for gradual lipid droplet formation during adipogenesis. Biochimica et biophysica acta. Molecular cell research 28 28499918
2014 New strategies to inhibit KEAP1 and the Cul3-based E3 ubiquitin ligases. Biochemical Society transactions 28 24450635
2022 CUL3/SPOP complex prevents immune escape and enhances chemotherapy sensitivity of ovarian cancer cells through degradation of PD-L1 protein. Journal for immunotherapy of cancer 26 36198437
2017 The CUL3-SPOP-DAXX axis is a novel regulator of VEGFR2 expression in vascular endothelial cells. Scientific reports 26 28216678
2016 Salvianolic acid A ameliorates the integrity of blood-spinal cord barrier via miR-101/Cul3/Nrf2/HO-1 signaling pathway. Brain research 26 28011395
2014 Unique pattern of component gene disruption in the NRF2 inhibitor KEAP1/CUL3/RBX1 E3-ubiquitin ligase complex in serous ovarian cancer. BioMed research international 26 25114896
2023 Structural and biochemical characterization establishes a detailed understanding of KEAP1-CUL3 complex assembly. Free radical biology & medicine 25 37156295
2021 Novel CUL3 Variant Causing Familial Hyperkalemic Hypertension Impairs Regulation and Function of Ubiquitin Ligase Activity. Hypertension (Dallas, Tex. : 1979) 25 34878901
2018 Renal COP9 Signalosome Deficiency Alters CUL3-KLHL3-WNK Signaling Pathway. Journal of the American Society of Nephrology : JASN 24 30301860
2004 Saccharomyces cerevisiae ubiquitin-like protein Rub1 conjugates to cullin proteins Rtt101 and Cul3 in vivo. The Biochemical journal 24 14519104
2001 In vitro ubiquitination of cyclin D1 by ROC1-CUL1 and ROC1-CUL3. FEBS letters 24 11311237
2013 CUL3 gene analysis enables early intervention for pediatric pseudohypoaldosteronism type II in infancy. Pediatric nephrology (Berlin, Germany) 23 23689903
2021 LZTR1: A promising adaptor of the CUL3 family. Oncology letters 22 34113392
2013 A quantitative proteomic analysis uncovers the relevance of CUL3 in bladder cancer aggressiveness. PloS one 22 23308193
2013 Analysis of dimerization of BTB-IVR domains of Keap1 and its interaction with Cul3, by molecular modeling. Bioinformation 21 23847398
2007 Suppression of Hedgehog signaling by Cul3 ligases in proliferation control of retinal precursors. Developmental biology 21 17559828
2023 Exo-miR-1290-induced by COX-2 overexpression promotes cancer-associated fibroblasts activation and tumor progression by CUL3-Nrf2 pathway in lung adenocarcinoma. Cell communication and signaling : CCS 20 37723559
2022 The functions and effects of CUL3-E3 ligases mediated non-degradative ubiquitination. Gene 20 35580799
2009 PEST sequences mediate heat shock factor 2 turnover by interacting with the Cul3 subunit of the Cul3-RING ubiquitin ligase. Cell stress & chaperones 20 19768582
2007 A Cul3-based E3 ligase regulates mitosis and is required to maintain the spindle assembly checkpoint in human cells. Cell cycle (Georgetown, Tex.) 20 18075312
2024 Loss-of-Function Variants in CUL3 Cause a Syndromic Neurodevelopmental Disorder. Annals of neurology 19 39301775
2013 CUL3 and protein kinases: insights from PLK1/KLHL22 interaction. Cell cycle (Georgetown, Tex.) 19 24067371
2020 miR-23a-3p increases endometrial receptivity via CUL3 during embryo implantation. Journal of molecular endocrinology 18 32716006
2016 Cul3-KLHL20 ubiquitin ligase: physiological functions, stress responses, and disease implications. Cell division 18 27042198