{"gene":"DCAF11","run_date":"2026-06-09T22:57:19","timeline":{"discoveries":[{"year":2009,"finding":"WDR-23 (DCAF11 ortholog in C. elegans) interacts with the CUL-4/DDB-1 ubiquitin ligase complex to repress SKN-1 protein levels, nuclear accumulation, and transcriptional activity, presumably targeting SKN-1 for proteasomal degradation.","method":"Genetic screen, co-immunoprecipitation, loss-of-function analysis in C. elegans","journal":"Molecular and cellular biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP and genetic epistasis in C. elegans, single lab, multiple genetic methods; degradation described as presumptive","pmids":["19273594"],"is_preprint":false},{"year":2014,"finding":"WDR-23 directly interacts with SKN-1c through a β-propeller structure (top face) and four motifs at the termini of SKN-1c, blocking SKN-1c binding to target DNA promoter sequences in a mechanism independent of the ubiquitin-proteasome system.","method":"Forward genetics, biochemical interaction assays, homology modeling, DNA-binding competition assays","journal":"Molecular and cellular biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct interaction and DNA-binding inhibition demonstrated biochemically; single lab with multiple orthogonal methods","pmids":["24912676"],"is_preprint":false},{"year":2016,"finding":"CRL4(WDR23) (the mammalian DCAF11-containing E3 ligase) binds and ubiquitylates SLBP (stem-loop binding protein) in vitro and in vivo, activating SLBP function in histone mRNA 3' end processing without affecting SLBP protein levels, thereby ensuring histone supply during DNA replication.","method":"In vitro ubiquitylation assay, co-immunoprecipitation, siRNA knockdown, cell-based histone mRNA processing assays","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro reconstitution of ubiquitylation, confirmed in vivo, multiple orthogonal methods in a single rigorous study","pmids":["27203182"],"is_preprint":false},{"year":2016,"finding":"DCAF11 acts as the substrate receptor of CRL4 to mediate proteasomal degradation of SLBP at the end of S phase; this interaction requires phosphorylation of SLBP at Thr61, and DCAF11 cannot bind the Thr61Ala mutant SLBP that is stable at S/G2.","method":"GST pull-down with phosphorylated SLBP fragment, co-immunoprecipitation, ectopic expression, siRNA knockdown","journal":"Cell cycle","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — phospho-dependent interaction confirmed by pull-down and Co-IP with mutant validation; single lab, multiple methods","pmids":["27254819"],"is_preprint":false},{"year":2017,"finding":"CUL4B forms an E3 ligase complex with RBX1, DDB1, and DCAF11 (CRL4B-DCAF11) in human osteosarcoma cells; this complex specifically ubiquitinates p21Cip1 at K16, K154, K161, and K163 (but not K75 or K141), promoting p21 degradation and cell cycle progression.","method":"In vitro and in vivo ubiquitination assays, site-directed mutagenesis of p21 lysine residues, shRNA knockdown of complex components, cell cycle analysis","journal":"Scientific reports","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro ubiquitination reconstitution with mutagenesis to map specific lysines, confirmed in vivo with functional cell cycle readout","pmids":["28446751"],"is_preprint":false},{"year":2017,"finding":"WDR23 (DCAF11) binds the DIDLID sequence within the Neh2 domain of NRF2 to regulate NRF2 stability via the DDB1-CUL4 complex, independent of the KEAP1-binding DLG and ETGE motifs; the conserved C-terminal domain of WDR23 is required for this CUL4 complex-mediated regulation.","method":"Co-immunoprecipitation, domain deletion analysis, human cell culture models, C. elegans genetic experiments","journal":"PLoS genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP and domain mapping in two model systems; single lab but orthogonal approaches","pmids":["28453520"],"is_preprint":false},{"year":2019,"finding":"Nuclear WDR-23B isoform promotes proteasome-dependent ubiquitination and turnover of substrates (including SKN-1), while cytoplasmic WDR-23A performs a proteasome-independent role; GEN-1 (a Holliday junction resolvase) is identified as an evolutionarily conserved WDR-23 substrate.","method":"Isoform-specific C. elegans expression constructs, genetic loss-of-function, double-strand break repair assays, stress survival assays","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — isoform-specific genetic experiments with functional readouts; single lab with multiple genetic methods","pmids":["31409866"],"is_preprint":false},{"year":2019,"finding":"TFEB represses DCAF11 at both protein and mRNA levels, reducing DCAF11-mediated ubiquitination of NRF2 and thereby stabilizing NRF2 protein.","method":"Stable cell lines expressing TFEB, western blot for ubiquitinated NRF2 fractions, mRNA and protein level measurements of DCAF11","journal":"Scientific reports","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single cell model, correlation-based without direct mechanistic reconstitution of TFEB-DCAF11 regulation","pmids":["31586112"],"is_preprint":false},{"year":2020,"finding":"Dcaf11 targets KAP1 (KRAB-associated protein 1) for ubiquitination-mediated degradation in early mouse embryos, leading to activation of the Zscan4 downstream enhancer and removal of heterochromatic H3K9me3 marks at telomere/subtelomere regions, enabling telomere sister-chromatid exchange and telomere lengthening.","method":"Dcaf11 knockout mice and ESCs, telomere FISH, ChIP for H3K9me3, ubiquitination assays for KAP1, T-SCE analysis, hematopoietic stem cell functional assays","journal":"Cell stem cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — KO mouse model with multiple orthogonal mechanistic readouts (ubiquitination, ChIP, T-SCE, functional HSC assays) in a single rigorous study","pmids":["33357405"],"is_preprint":false},{"year":2020,"finding":"WDR23 (DCAF11) physically interacts with NRF2 in mammalian cells (HeLa and Hep3B) and knockdown of WDR23 stabilizes NRF2 protein and alters expression of drug-metabolizing enzymes; WDR23 isoform 1 localizes to the cytoplasm and isoform 2 to the nucleus.","method":"Co-immunoprecipitation, siRNA knockdown, immunostaining, western blot","journal":"Drug metabolism and pharmacokinetics","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct binding confirmed by Co-IP; replicated across two cell lines; isoform localization by immunostaining","pmids":["32839090"],"is_preprint":false},{"year":2021,"finding":"Electrophilic PROTACs covalently modify specific cysteines in DCAF11, enabling DCAF11 (acting as a CUL4 E3 ligase substrate adaptor) to support ligand-induced proteasomal degradation of multiple endogenous proteins including FKBP12 and the androgen receptor in human prostate cancer cells.","method":"Functional PROTAC screening, mass spectrometry-based cysteine identification, cellular degradation assays, mechanistic target validation","journal":"Journal of the American Chemical Society","confidence":"High","confidence_rationale":"Tier 2 / Strong — covalent cysteine modification mechanistically defined by MS, degradation confirmed for multiple endogenous substrates, multiple orthogonal methods in one study","pmids":["33783207"],"is_preprint":false},{"year":2021,"finding":"DCAF11 mediates polyubiquitination of CENP-A at K49 and K124, with this ubiquitination primed by phosphorylation of CENP-A Ser68; deletion of DCAF11 impairs CENP-A degradation during mitosis and causes CENP-A mislocalization to non-centromeric regions.","method":"Co-immunoprecipitation, ubiquitination assays, site-directed mutagenesis (K49R/K124R), DCAF11 knockout cell lines, immunofluorescence microscopy","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — phospho-dependent substrate recognition confirmed with mutagenesis mapping ubiquitination sites, KO phenotype validated with localization readout; multiple orthogonal methods","pmids":["34758320"],"is_preprint":false},{"year":2021,"finding":"Sp1 regulates CUL4A expression via the Sp1_M4 binding site, modulating the activity of the CRL4A-WDR23 (DCAF11) ubiquitin ligase complex toward NRF2; WDR23 knockdown abrogates the Sp1-dependent effect on NRF2 protein levels.","method":"Keap1/Sp1 knockdown, promoter-reporter assays, Co-IP, western blot, genetic epistasis (double knockdown)","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — epistasis (double KD) and Co-IP support pathway placement; single lab with multiple genetic methods","pmids":["33895141"],"is_preprint":false},{"year":2023,"finding":"Arylidene-indolinone compounds covalently bind DCAF11 as a substrate receptor in the CUL4A/B-RBX1-DDB1-DCAF11 E3 ligase, enabling PROTAC-mediated ubiquitin-proteasome-dependent degradation of target proteins (BRD2/3/4, BTK, BLK).","method":"Target identification by chemical proteomics, cellular degradation assays, mechanistic studies confirming UPS pathway","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — covalent binding to DCAF11 identified by chemical proteomics; degradation mechanism confirmed; single lab","pmids":["38036533"],"is_preprint":false},{"year":2024,"finding":"PLX-3618 induces selective UPS-mediated degradation of BRD4 by forming a BRD4:PLX-3618:DCAF11 ternary complex; mutational studies of DCAF11 provide further mechanistic insights into this degradation mechanism.","method":"Cell-based degradation assays, protein-protein interaction studies (ternary complex), DCAF11 mutagenesis, in vivo tumor models","journal":"Molecular cancer therapeutics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ternary complex formation demonstrated biochemically and validated by mutagenesis; single lab with multiple methods","pmids":["38907538"],"is_preprint":false},{"year":2024,"finding":"Loss of WDR23 (DCAF11) in mouse liver increases IDE (insulin-degrading enzyme) expression via NRF2-mediated transcriptional upregulation, leading to reduced circulating insulin and dysregulated insulin signaling; NRF2 is a direct target of WDR23-CUL4 proteostasis that mediates this hepatic IDE regulatory axis.","method":"Wdr23KO mice, human cell models with WDR23 deletion, IDE chemical inhibition, phosphorylation analysis of insulin signaling cascade proteins","journal":"GeroScience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic KO with defined molecular mechanism (NRF2→IDE) and chemical rescue; single lab, multiple orthogonal approaches","pmids":["38767782"],"is_preprint":false},{"year":2024,"finding":"SNAr covalent warheads appended to small molecule inhibitors can recruit DCAF11 (among other E3 ligases) to induce targeted protein degradation, demonstrating that DCAF11 can accommodate diverse electrophilic chemistries for covalent engagement.","method":"Chemical biology screening, cellular degradation assays, E3 ligase identification by proteomics","journal":"bioRxiv","confidence":"Low","confidence_rationale":"Tier 3 / Weak — preprint, single lab, DCAF11 recruitment is one of several ligases identified; limited mechanistic detail for DCAF11 specifically","pmids":["bio_10.1101_2024.09.25.615094"],"is_preprint":true}],"current_model":"DCAF11 (WDR23) is a substrate receptor of the CUL4-DDB1 E3 ubiquitin ligase complex (CRL4-DCAF11) that targets multiple substrates—including NRF2/SKN-1, p21, SLBP, CENP-A, and KAP1—for ubiquitination and proteasomal degradation through phosphorylation-dependent recognition mechanisms, and can also directly block SKN-1/NRF DNA-binding independent of the proteasome; additionally, specific cysteines in DCAF11 can be covalently engaged by electrophilic small molecules to redirect the E3 ligase toward neo-substrates for targeted protein degradation."},"narrative":{"mechanistic_narrative":"DCAF11 (WDR23) is the substrate-recognition receptor of a CUL4-DDB1-RBX1 (CRL4) E3 ubiquitin ligase that controls the abundance and activity of a defined set of substrates governing stress response, cell cycle, and chromatin [PMID:19273594, PMID:27203182, PMID:28446751]. Its founding role, defined through the C. elegans ortholog WDR-23, is repression of the NRF2/SKN-1 antioxidant transcription factor: DCAF11 routes NRF2 for CRL4-mediated turnover by engaging the DIDLID sequence in the NRF2 Neh2 domain, distinct from the KEAP1-binding motifs, with the conserved C-terminal domain of WDR23 required for ligase coupling [PMID:28453520, PMID:32839090]; in C. elegans it can additionally bind SKN-1 through its β-propeller and directly block its DNA binding independent of the proteasome [PMID:24912676]. Beyond NRF2, DCAF11 acts through phosphorylation-primed substrate recognition: it degrades SLBP at the end of S phase in a manner requiring SLBP Thr61 phosphorylation [PMID:27254819], ubiquitinates p21Cip1 at defined lysines to promote cell-cycle progression [PMID:28446751], and targets phospho-Ser68-primed CENP-A at K49/K124 to enforce centromeric identity, with its loss causing CENP-A mislocalization [PMID:34758320]. It also degrades KAP1 in early embryos to derepress Zscan4 and enable telomere lengthening [PMID:33357405]. Distinct nuclear and cytoplasmic isoforms partition proteasome-dependent and proteasome-independent functions [PMID:31409866, PMID:32839090]. DCAF11 is a productive handle for targeted protein degradation: specific cysteines can be covalently engaged by electrophilic PROTACs to redirect the ligase toward neo-substrates including FKBP12, the androgen receptor, and BRD4 [PMID:33783207, PMID:38036533, PMID:38907538].","teleology":[{"year":2009,"claim":"Established DCAF11/WDR-23 as a CRL4-associated negative regulator of the NRF2/SKN-1 stress-response transcription factor, defining its core biological role.","evidence":"Genetic screen, Co-IP and loss-of-function epistasis in C. elegans","pmids":["19273594"],"confidence":"Medium","gaps":["Proteasomal degradation was presumptive, not directly reconstituted","Did not map the WDR-23–SKN-1 interaction interface"]},{"year":2014,"claim":"Showed DCAF11 has a proteasome-independent mode—directly binding SKN-1c via its β-propeller and blocking DNA binding—revealing dual mechanisms of substrate control.","evidence":"Forward genetics, biochemical interaction and DNA-binding competition assays, homology modeling in C. elegans","pmids":["24912676"],"confidence":"Medium","gaps":["Structural model based on homology, not experimental structure","Relative contribution of degradation vs. DNA-block in vivo not quantified"]},{"year":2016,"claim":"Defined SLBP as a mammalian substrate, demonstrating DCAF11 both activates SLBP function via ubiquitylation and later degrades it in a phospho-Thr61-dependent manner, linking the ligase to histone supply and cell-cycle timing.","evidence":"In vitro ubiquitylation reconstitution, Co-IP, GST pull-down with phospho-peptides, siRNA, mutant validation","pmids":["27203182","27254819"],"confidence":"High","gaps":["Kinase generating the Thr61 phosphomark not identified","How non-degradative vs. degradative ubiquitylation of SLBP is switched is unresolved"]},{"year":2017,"claim":"Extended the substrate repertoire to cell-cycle regulators (p21Cip1) and mapped the NRF2 recognition determinant, distinguishing the DCAF11 pathway from KEAP1.","evidence":"In vitro/in vivo ubiquitination with lysine-mapping mutagenesis, domain-deletion Co-IP, shRNA, cell-cycle analysis in human cells and C. elegans","pmids":["28446751","28453520"],"confidence":"High","gaps":["Whether p21 and NRF2 recognition require phosphorylation not established","Physiological balance between KEAP1 and DCAF11 control of NRF2 unclear"]},{"year":2019,"claim":"Resolved that nuclear and cytoplasmic WDR-23 isoforms execute proteasome-dependent and proteasome-independent functions respectively, and identified GEN-1 as a conserved substrate.","evidence":"Isoform-specific expression constructs, genetic loss-of-function, DSB-repair and stress assays in C. elegans; TFEB regulation in cells","pmids":["31409866","31586112"],"confidence":"Medium","gaps":["TFEB-DCAF11 regulation is correlative, not mechanistically reconstituted","Conservation of GEN-1 targeting in mammals untested"]},{"year":2020,"claim":"Connected DCAF11 to chromatin and telomere biology by showing KAP1 degradation derepresses Zscan4 and drives telomere lengthening, and confirmed direct NRF2 binding with isoform-resolved localization in human cells.","evidence":"Dcaf11 KO mice/ESCs, telomere FISH, H3K9me3 ChIP, KAP1 ubiquitination, T-SCE, HSC assays; Co-IP and immunostaining in HeLa/Hep3B","pmids":["33357405","32839090"],"confidence":"High","gaps":["Recognition signal on KAP1 not defined","Tissue-specific substrate selectivity not mapped"]},{"year":2021,"claim":"Demonstrated phospho-primed recognition of CENP-A enforces centromeric identity, and identified covalent cysteine engagement that converts DCAF11 into a programmable degradation receptor.","evidence":"Ubiquitination assays with site mutagenesis, DCAF11 KO cells, immunofluorescence; PROTAC screening with MS-based cysteine mapping and degradation of FKBP12/AR; Sp1→CUL4A epistasis on NRF2","pmids":["34758320","33783207","33895141"],"confidence":"High","gaps":["Kinase priming CENP-A Ser68 in this context not identified","Structural basis of covalent cysteine ligand engagement undefined"]},{"year":2024,"claim":"Consolidated DCAF11 as a versatile targeted-degradation handle accommodating diverse electrophilic chemistries, and linked WDR23-NRF2 proteostasis to hepatic insulin metabolism via IDE.","evidence":"Chemical proteomics and ternary-complex/mutagenesis studies (BRD2/3/4, BTK, BLK, BRD4); Wdr23 KO mice with NRF2→IDE axis and chemical rescue","pmids":["38036533","38907538","38767782"],"confidence":"Medium","gaps":["Cysteine residues engaged by distinct chemistries not uniformly mapped","Physiological NRF2-IDE axis tested in single model system"]},{"year":null,"claim":"An experimental structure of DCAF11 bound to substrates or covalent ligands, and a unifying account of how phospho-degron recognition is shared across its diverse substrates, remain to be established.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No experimental structure of the DCAF11 β-propeller with any substrate","Common rules of phospho-degron recognition across SLBP, CENP-A, and others not unified","Endogenous substrate landscape likely incomplete"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[2,4,8,11]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0,1,5]},{"term_id":"GO:0016874","term_label":"ligase activity","supporting_discovery_ids":[2,4,11]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[6,9]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[6,9]}],"pathway":[{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[2,4,11]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[3,4,11]},{"term_id":"R-HSA-8953897","term_label":"Cellular responses to stimuli","supporting_discovery_ids":[0,5]},{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[8,11]}],"complexes":["CRL4-DCAF11 (CUL4-DDB1-RBX1-DCAF11) E3 ubiquitin ligase"],"partners":["CUL4A","CUL4B","DDB1","RBX1","NRF2","SLBP","CENP-A","KAP1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q8TEB1","full_name":"DDB1- and CUL4-associated factor 11","aliases":["WD repeat-containing protein 23"],"length_aa":546,"mass_kda":61.7,"function":"May function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/Q8TEB1/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/DCAF11","classification":"Not Classified","n_dependent_lines":2,"n_total_lines":1208,"dependency_fraction":0.0016556291390728477},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"DDB1","stoichiometry":4.0},{"gene":"ANAPC4","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/DCAF11","total_profiled":1310},"omim":[{"mim_id":"613317","title":"DDB1- AND CUL4-ASSOCIATED FACTOR 11; DCAF11","url":"https://www.omim.org/entry/613317"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Nucleoplasm","reliability":"Enhanced"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/DCAF11"},"hgnc":{"alias_symbol":["PRO2389","GL014"],"prev_symbol":["WDR23"]},"alphafold":{"accession":"Q8TEB1","domains":[{"cath_id":"2.130.10.10","chopping":"176-446","consensus_level":"high","plddt":95.4394,"start":176,"end":446}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8TEB1","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8TEB1-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8TEB1-F1-predicted_aligned_error_v6.png","plddt_mean":82.69},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=DCAF11","jax_strain_url":"https://www.jax.org/strain/search?query=DCAF11"},"sequence":{"accession":"Q8TEB1","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8TEB1.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8TEB1/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8TEB1"}},"corpus_meta":[{"pmid":"19273594","id":"PMC_19273594","title":"The WD40 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of WDR23 proteostasis impacts mitochondrial homeostasis in the mouse brain.","date":"2024","source":"Cellular signalling","url":"https://pubmed.ncbi.nlm.nih.gov/38242270","citation_count":1,"is_preprint":false},{"pmid":"40320794","id":"PMC_40320794","title":"Loss of WDR23 slows the rate of age-related cognitive decline with elevated amyloid burden.","date":"2025","source":"Journal of Alzheimer's disease : JAD","url":"https://pubmed.ncbi.nlm.nih.gov/40320794","citation_count":1,"is_preprint":false},{"pmid":"41628916","id":"PMC_41628916","title":"Arylidene-Thiazoldione Scaffold Acts as the E3 Ligand of DCAF11 for PROTAC Design.","date":"2026","source":"Journal of medicinal chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/41628916","citation_count":0,"is_preprint":false},{"pmid":"41740371","id":"PMC_41740371","title":"Flow-dependent NRF2 dysfunction via KEAP1/WDR23 dual repression contributes to endothelial oxidative damage in venous disease.","date":"2026","source":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","url":"https://pubmed.ncbi.nlm.nih.gov/41740371","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2024.09.25.615094","title":"Discovery of electrophilic degraders that exploit SNAr chemistry","date":"2024-09-27","source":"bioRxiv","url":"https://doi.org/10.1101/2024.09.25.615094","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":14103,"output_tokens":4067,"usd":0.051657,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":11860,"output_tokens":3572,"usd":0.0743,"stage2_stop_reason":"end_turn"},"total_usd":0.125957,"stage1_batch_id":"msgbatch_01ACAxJQabDsht39JXeWG22d","stage2_batch_id":"msgbatch_01QEU22A9U5sbPTgsMzTmvSf","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2009,\n      \"finding\": \"WDR-23 (DCAF11 ortholog in C. elegans) interacts with the CUL-4/DDB-1 ubiquitin ligase complex to repress SKN-1 protein levels, nuclear accumulation, and transcriptional activity, presumably targeting SKN-1 for proteasomal degradation.\",\n      \"method\": \"Genetic screen, co-immunoprecipitation, loss-of-function analysis in C. elegans\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP and genetic epistasis in C. elegans, single lab, multiple genetic methods; degradation described as presumptive\",\n      \"pmids\": [\"19273594\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"WDR-23 directly interacts with SKN-1c through a β-propeller structure (top face) and four motifs at the termini of SKN-1c, blocking SKN-1c binding to target DNA promoter sequences in a mechanism independent of the ubiquitin-proteasome system.\",\n      \"method\": \"Forward genetics, biochemical interaction assays, homology modeling, DNA-binding competition assays\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct interaction and DNA-binding inhibition demonstrated biochemically; single lab with multiple orthogonal methods\",\n      \"pmids\": [\"24912676\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"CRL4(WDR23) (the mammalian DCAF11-containing E3 ligase) binds and ubiquitylates SLBP (stem-loop binding protein) in vitro and in vivo, activating SLBP function in histone mRNA 3' end processing without affecting SLBP protein levels, thereby ensuring histone supply during DNA replication.\",\n      \"method\": \"In vitro ubiquitylation assay, co-immunoprecipitation, siRNA knockdown, cell-based histone mRNA processing assays\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro reconstitution of ubiquitylation, confirmed in vivo, multiple orthogonal methods in a single rigorous study\",\n      \"pmids\": [\"27203182\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"DCAF11 acts as the substrate receptor of CRL4 to mediate proteasomal degradation of SLBP at the end of S phase; this interaction requires phosphorylation of SLBP at Thr61, and DCAF11 cannot bind the Thr61Ala mutant SLBP that is stable at S/G2.\",\n      \"method\": \"GST pull-down with phosphorylated SLBP fragment, co-immunoprecipitation, ectopic expression, siRNA knockdown\",\n      \"journal\": \"Cell cycle\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — phospho-dependent interaction confirmed by pull-down and Co-IP with mutant validation; single lab, multiple methods\",\n      \"pmids\": [\"27254819\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"CUL4B forms an E3 ligase complex with RBX1, DDB1, and DCAF11 (CRL4B-DCAF11) in human osteosarcoma cells; this complex specifically ubiquitinates p21Cip1 at K16, K154, K161, and K163 (but not K75 or K141), promoting p21 degradation and cell cycle progression.\",\n      \"method\": \"In vitro and in vivo ubiquitination assays, site-directed mutagenesis of p21 lysine residues, shRNA knockdown of complex components, cell cycle analysis\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro ubiquitination reconstitution with mutagenesis to map specific lysines, confirmed in vivo with functional cell cycle readout\",\n      \"pmids\": [\"28446751\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"WDR23 (DCAF11) binds the DIDLID sequence within the Neh2 domain of NRF2 to regulate NRF2 stability via the DDB1-CUL4 complex, independent of the KEAP1-binding DLG and ETGE motifs; the conserved C-terminal domain of WDR23 is required for this CUL4 complex-mediated regulation.\",\n      \"method\": \"Co-immunoprecipitation, domain deletion analysis, human cell culture models, C. elegans genetic experiments\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP and domain mapping in two model systems; single lab but orthogonal approaches\",\n      \"pmids\": [\"28453520\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Nuclear WDR-23B isoform promotes proteasome-dependent ubiquitination and turnover of substrates (including SKN-1), while cytoplasmic WDR-23A performs a proteasome-independent role; GEN-1 (a Holliday junction resolvase) is identified as an evolutionarily conserved WDR-23 substrate.\",\n      \"method\": \"Isoform-specific C. elegans expression constructs, genetic loss-of-function, double-strand break repair assays, stress survival assays\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — isoform-specific genetic experiments with functional readouts; single lab with multiple genetic methods\",\n      \"pmids\": [\"31409866\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"TFEB represses DCAF11 at both protein and mRNA levels, reducing DCAF11-mediated ubiquitination of NRF2 and thereby stabilizing NRF2 protein.\",\n      \"method\": \"Stable cell lines expressing TFEB, western blot for ubiquitinated NRF2 fractions, mRNA and protein level measurements of DCAF11\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single cell model, correlation-based without direct mechanistic reconstitution of TFEB-DCAF11 regulation\",\n      \"pmids\": [\"31586112\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Dcaf11 targets KAP1 (KRAB-associated protein 1) for ubiquitination-mediated degradation in early mouse embryos, leading to activation of the Zscan4 downstream enhancer and removal of heterochromatic H3K9me3 marks at telomere/subtelomere regions, enabling telomere sister-chromatid exchange and telomere lengthening.\",\n      \"method\": \"Dcaf11 knockout mice and ESCs, telomere FISH, ChIP for H3K9me3, ubiquitination assays for KAP1, T-SCE analysis, hematopoietic stem cell functional assays\",\n      \"journal\": \"Cell stem cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — KO mouse model with multiple orthogonal mechanistic readouts (ubiquitination, ChIP, T-SCE, functional HSC assays) in a single rigorous study\",\n      \"pmids\": [\"33357405\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"WDR23 (DCAF11) physically interacts with NRF2 in mammalian cells (HeLa and Hep3B) and knockdown of WDR23 stabilizes NRF2 protein and alters expression of drug-metabolizing enzymes; WDR23 isoform 1 localizes to the cytoplasm and isoform 2 to the nucleus.\",\n      \"method\": \"Co-immunoprecipitation, siRNA knockdown, immunostaining, western blot\",\n      \"journal\": \"Drug metabolism and pharmacokinetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct binding confirmed by Co-IP; replicated across two cell lines; isoform localization by immunostaining\",\n      \"pmids\": [\"32839090\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Electrophilic PROTACs covalently modify specific cysteines in DCAF11, enabling DCAF11 (acting as a CUL4 E3 ligase substrate adaptor) to support ligand-induced proteasomal degradation of multiple endogenous proteins including FKBP12 and the androgen receptor in human prostate cancer cells.\",\n      \"method\": \"Functional PROTAC screening, mass spectrometry-based cysteine identification, cellular degradation assays, mechanistic target validation\",\n      \"journal\": \"Journal of the American Chemical Society\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — covalent cysteine modification mechanistically defined by MS, degradation confirmed for multiple endogenous substrates, multiple orthogonal methods in one study\",\n      \"pmids\": [\"33783207\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"DCAF11 mediates polyubiquitination of CENP-A at K49 and K124, with this ubiquitination primed by phosphorylation of CENP-A Ser68; deletion of DCAF11 impairs CENP-A degradation during mitosis and causes CENP-A mislocalization to non-centromeric regions.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitination assays, site-directed mutagenesis (K49R/K124R), DCAF11 knockout cell lines, immunofluorescence microscopy\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — phospho-dependent substrate recognition confirmed with mutagenesis mapping ubiquitination sites, KO phenotype validated with localization readout; multiple orthogonal methods\",\n      \"pmids\": [\"34758320\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Sp1 regulates CUL4A expression via the Sp1_M4 binding site, modulating the activity of the CRL4A-WDR23 (DCAF11) ubiquitin ligase complex toward NRF2; WDR23 knockdown abrogates the Sp1-dependent effect on NRF2 protein levels.\",\n      \"method\": \"Keap1/Sp1 knockdown, promoter-reporter assays, Co-IP, western blot, genetic epistasis (double knockdown)\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — epistasis (double KD) and Co-IP support pathway placement; single lab with multiple genetic methods\",\n      \"pmids\": [\"33895141\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Arylidene-indolinone compounds covalently bind DCAF11 as a substrate receptor in the CUL4A/B-RBX1-DDB1-DCAF11 E3 ligase, enabling PROTAC-mediated ubiquitin-proteasome-dependent degradation of target proteins (BRD2/3/4, BTK, BLK).\",\n      \"method\": \"Target identification by chemical proteomics, cellular degradation assays, mechanistic studies confirming UPS pathway\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — covalent binding to DCAF11 identified by chemical proteomics; degradation mechanism confirmed; single lab\",\n      \"pmids\": [\"38036533\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"PLX-3618 induces selective UPS-mediated degradation of BRD4 by forming a BRD4:PLX-3618:DCAF11 ternary complex; mutational studies of DCAF11 provide further mechanistic insights into this degradation mechanism.\",\n      \"method\": \"Cell-based degradation assays, protein-protein interaction studies (ternary complex), DCAF11 mutagenesis, in vivo tumor models\",\n      \"journal\": \"Molecular cancer therapeutics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ternary complex formation demonstrated biochemically and validated by mutagenesis; single lab with multiple methods\",\n      \"pmids\": [\"38907538\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Loss of WDR23 (DCAF11) in mouse liver increases IDE (insulin-degrading enzyme) expression via NRF2-mediated transcriptional upregulation, leading to reduced circulating insulin and dysregulated insulin signaling; NRF2 is a direct target of WDR23-CUL4 proteostasis that mediates this hepatic IDE regulatory axis.\",\n      \"method\": \"Wdr23KO mice, human cell models with WDR23 deletion, IDE chemical inhibition, phosphorylation analysis of insulin signaling cascade proteins\",\n      \"journal\": \"GeroScience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic KO with defined molecular mechanism (NRF2→IDE) and chemical rescue; single lab, multiple orthogonal approaches\",\n      \"pmids\": [\"38767782\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"SNAr covalent warheads appended to small molecule inhibitors can recruit DCAF11 (among other E3 ligases) to induce targeted protein degradation, demonstrating that DCAF11 can accommodate diverse electrophilic chemistries for covalent engagement.\",\n      \"method\": \"Chemical biology screening, cellular degradation assays, E3 ligase identification by proteomics\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — preprint, single lab, DCAF11 recruitment is one of several ligases identified; limited mechanistic detail for DCAF11 specifically\",\n      \"pmids\": [\"bio_10.1101_2024.09.25.615094\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"DCAF11 (WDR23) is a substrate receptor of the CUL4-DDB1 E3 ubiquitin ligase complex (CRL4-DCAF11) that targets multiple substrates—including NRF2/SKN-1, p21, SLBP, CENP-A, and KAP1—for ubiquitination and proteasomal degradation through phosphorylation-dependent recognition mechanisms, and can also directly block SKN-1/NRF DNA-binding independent of the proteasome; additionally, specific cysteines in DCAF11 can be covalently engaged by electrophilic small molecules to redirect the E3 ligase toward neo-substrates for targeted protein degradation.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"DCAF11 (WDR23) is the substrate-recognition receptor of a CUL4-DDB1-RBX1 (CRL4) E3 ubiquitin ligase that controls the abundance and activity of a defined set of substrates governing stress response, cell cycle, and chromatin [#0, #2, #4]. Its founding role, defined through the C. elegans ortholog WDR-23, is repression of the NRF2/SKN-1 antioxidant transcription factor: DCAF11 routes NRF2 for CRL4-mediated turnover by engaging the DIDLID sequence in the NRF2 Neh2 domain, distinct from the KEAP1-binding motifs, with the conserved C-terminal domain of WDR23 required for ligase coupling [#5, #9]; in C. elegans it can additionally bind SKN-1 through its \\u03b2-propeller and directly block its DNA binding independent of the proteasome [#1]. Beyond NRF2, DCAF11 acts through phosphorylation-primed substrate recognition: it degrades SLBP at the end of S phase in a manner requiring SLBP Thr61 phosphorylation [#3], ubiquitinates p21Cip1 at defined lysines to promote cell-cycle progression [#4], and targets phospho-Ser68-primed CENP-A at K49/K124 to enforce centromeric identity, with its loss causing CENP-A mislocalization [#11]. It also degrades KAP1 in early embryos to derepress Zscan4 and enable telomere lengthening [#8]. Distinct nuclear and cytoplasmic isoforms partition proteasome-dependent and proteasome-independent functions [#6, #9]. DCAF11 is a productive handle for targeted protein degradation: specific cysteines can be covalently engaged by electrophilic PROTACs to redirect the ligase toward neo-substrates including FKBP12, the androgen receptor, and BRD4 [#10, #13, #14].\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"Established DCAF11/WDR-23 as a CRL4-associated negative regulator of the NRF2/SKN-1 stress-response transcription factor, defining its core biological role.\",\n      \"evidence\": \"Genetic screen, Co-IP and loss-of-function epistasis in C. elegans\",\n      \"pmids\": [\"19273594\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Proteasomal degradation was presumptive, not directly reconstituted\", \"Did not map the WDR-23\\u2013SKN-1 interaction interface\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Showed DCAF11 has a proteasome-independent mode\\u2014directly binding SKN-1c via its \\u03b2-propeller and blocking DNA binding\\u2014revealing dual mechanisms of substrate control.\",\n      \"evidence\": \"Forward genetics, biochemical interaction and DNA-binding competition assays, homology modeling in C. elegans\",\n      \"pmids\": [\"24912676\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Structural model based on homology, not experimental structure\", \"Relative contribution of degradation vs. DNA-block in vivo not quantified\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Defined SLBP as a mammalian substrate, demonstrating DCAF11 both activates SLBP function via ubiquitylation and later degrades it in a phospho-Thr61-dependent manner, linking the ligase to histone supply and cell-cycle timing.\",\n      \"evidence\": \"In vitro ubiquitylation reconstitution, Co-IP, GST pull-down with phospho-peptides, siRNA, mutant validation\",\n      \"pmids\": [\"27203182\", \"27254819\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Kinase generating the Thr61 phosphomark not identified\", \"How non-degradative vs. degradative ubiquitylation of SLBP is switched is unresolved\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Extended the substrate repertoire to cell-cycle regulators (p21Cip1) and mapped the NRF2 recognition determinant, distinguishing the DCAF11 pathway from KEAP1.\",\n      \"evidence\": \"In vitro/in vivo ubiquitination with lysine-mapping mutagenesis, domain-deletion Co-IP, shRNA, cell-cycle analysis in human cells and C. elegans\",\n      \"pmids\": [\"28446751\", \"28453520\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Whether p21 and NRF2 recognition require phosphorylation not established\", \"Physiological balance between KEAP1 and DCAF11 control of NRF2 unclear\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Resolved that nuclear and cytoplasmic WDR-23 isoforms execute proteasome-dependent and proteasome-independent functions respectively, and identified GEN-1 as a conserved substrate.\",\n      \"evidence\": \"Isoform-specific expression constructs, genetic loss-of-function, DSB-repair and stress assays in C. elegans; TFEB regulation in cells\",\n      \"pmids\": [\"31409866\", \"31586112\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"TFEB-DCAF11 regulation is correlative, not mechanistically reconstituted\", \"Conservation of GEN-1 targeting in mammals untested\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Connected DCAF11 to chromatin and telomere biology by showing KAP1 degradation derepresses Zscan4 and drives telomere lengthening, and confirmed direct NRF2 binding with isoform-resolved localization in human cells.\",\n      \"evidence\": \"Dcaf11 KO mice/ESCs, telomere FISH, H3K9me3 ChIP, KAP1 ubiquitination, T-SCE, HSC assays; Co-IP and immunostaining in HeLa/Hep3B\",\n      \"pmids\": [\"33357405\", \"32839090\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Recognition signal on KAP1 not defined\", \"Tissue-specific substrate selectivity not mapped\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Demonstrated phospho-primed recognition of CENP-A enforces centromeric identity, and identified covalent cysteine engagement that converts DCAF11 into a programmable degradation receptor.\",\n      \"evidence\": \"Ubiquitination assays with site mutagenesis, DCAF11 KO cells, immunofluorescence; PROTAC screening with MS-based cysteine mapping and degradation of FKBP12/AR; Sp1\\u2192CUL4A epistasis on NRF2\",\n      \"pmids\": [\"34758320\", \"33783207\", \"33895141\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Kinase priming CENP-A Ser68 in this context not identified\", \"Structural basis of covalent cysteine ligand engagement undefined\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Consolidated DCAF11 as a versatile targeted-degradation handle accommodating diverse electrophilic chemistries, and linked WDR23-NRF2 proteostasis to hepatic insulin metabolism via IDE.\",\n      \"evidence\": \"Chemical proteomics and ternary-complex/mutagenesis studies (BRD2/3/4, BTK, BLK, BRD4); Wdr23 KO mice with NRF2\\u2192IDE axis and chemical rescue\",\n      \"pmids\": [\"38036533\", \"38907538\", \"38767782\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Cysteine residues engaged by distinct chemistries not uniformly mapped\", \"Physiological NRF2-IDE axis tested in single model system\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"An experimental structure of DCAF11 bound to substrates or covalent ligands, and a unifying account of how phospho-degron recognition is shared across its diverse substrates, remain to be established.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"No experimental structure of the DCAF11 \\u03b2-propeller with any substrate\", \"Common rules of phospho-degron recognition across SLBP, CENP-A, and others not unified\", \"Endogenous substrate landscape likely incomplete\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [2, 4, 8, 11]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 1, 5]},\n      {\"term_id\": \"GO:0016874\", \"supporting_discovery_ids\": [2, 4, 11]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [6, 9]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [6, 9]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [2, 4, 11]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [3, 4, 11]},\n      {\"term_id\": \"R-HSA-8953897\", \"supporting_discovery_ids\": [0, 5]},\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [8, 11]}\n    ],\n    \"complexes\": [\"CRL4-DCAF11 (CUL4-DDB1-RBX1-DCAF11) E3 ubiquitin ligase\"],\n    \"partners\": [\"CUL4A\", \"CUL4B\", \"DDB1\", \"RBX1\", \"NRF2\", \"SLBP\", \"CENP-A\", \"KAP1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}