{"gene":"CEP63","run_date":"2026-06-09T22:57:18","timeline":{"discoveries":[{"year":2009,"finding":"ATM and ATR phosphorylate Xenopus CEP63 (XCEP63) on Ser 560 following DNA double-strand breaks, promoting its delocalization from the centrosome and thereby inhibiting centrosome-driven spindle assembly. Mutation of XCEP63 Ser 560 to Ala prevented spindle assembly defects, and CEP63 gene inactivation in DT40 cells impaired spindle assembly and prevented ATM/ATR-dependent mitotic effects.","method":"In vitro Xenopus egg extract spindle assembly assay, site-directed mutagenesis (S560A), cDNA expression library screen for ATM/ATR substrates, CEP63 gene knockout in avian DT40 cells","journal":"Nature cell biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — reconstitution in Xenopus extract, active-site mutagenesis, and genetic knockout with defined phenotype across multiple systems","pmids":["19182792"],"is_preprint":false},{"year":2011,"finding":"Human CEP63 binds to and recruits CDK1 to centrosomes, regulating mitotic entry. RNAi-mediated CEP63 depletion in U2OS cells caused polyploidization through mitotic skipping associated with loss of centrosomal CDK1. CEP63 overexpression induced de novo centrosome amplification during interphase, suppressible by the CDK inhibitor roscovitine.","method":"Co-immunoprecipitation, RNAi knockdown with cell cycle phenotype readout (polyploidy, mitotic skipping), overexpression with CDK inhibitor rescue","journal":"Cancer research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP plus loss-of-function and gain-of-function with pharmacological rescue, single lab","pmids":["21406398"],"is_preprint":false},{"year":2013,"finding":"CEP63 regulates mother-centriole-dependent centriole duplication by binding to CEP152 and recruiting PLK4 to activate centriole biogenesis. Its paralogue DEUP1 (Cep63-derived) uses the same CEP152-binding mechanism to assemble deuterosomes for large-scale de novo centriole biogenesis in multiciliogenesis.","method":"Co-immunoprecipitation, RNAi knockdown in multiciliated cell differentiation assay, phylogenetic analysis, functional rescue experiments","journal":"Nature cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP for CEP63-CEP152-PLK4 interaction, loss-of-function with defined centriole duplication phenotype, replicated across multiple contexts","pmids":["24240477"],"is_preprint":false},{"year":2013,"finding":"CEP57, CEP63, and CEP152 form a ring-like complex localizing around the proximal end of centrioles, as revealed by selective chemical crosslinking combined with superresolution microscopy.","method":"Selective chemical crosslinking, superresolution microscopy (STORM/PALM), proximity-based interaction mapping of 31 centrosomal proteins","journal":"Current biology : CB","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — chemical crosslinking with superresolution imaging, single lab but two orthogonal methods","pmids":["23333316"],"is_preprint":false},{"year":2015,"finding":"CEP63-deficient mice develop microcephaly through p53-dependent apoptosis of neural progenitor cells triggered by centrosome-based mitotic errors (not aberrant DNA damage response). Brain size was rescued by p53 deletion. Additionally, CEP63 loss caused centrosome aberrations in spermatocytes, chromosome entanglements, and defective telomere clustering, leading to failed meiotic recombination and male infertility.","method":"Cep63 knockout mouse model, p53 double knockout epistasis, immunofluorescence of centrosome/chromosome defects, meiotic spread analysis","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic epistasis (p53 rescue of brain size), knockout mouse with defined cellular and organismal phenotypes, multiple orthogonal readouts","pmids":["26158450"],"is_preprint":false},{"year":2016,"finding":"Autophagy controls centrosome number by degrading CEP63. Autophagy-deficient cells accumulate extra centrosomes with multiple CEP63 dots. CEP63 is recruited to autophagosomes via interaction with p62 (a selective autophagy receptor). Upregulation of CEP63 increases centrosome number.","method":"Autophagy-deficient cell lines and p62-/- mouse hematopoietic cells, co-immunoprecipitation of CEP63 with p62, immunofluorescence of autophagosome-CEP63 co-localization, CEP63 overexpression phenotype","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — Co-IP identifying p62 as CEP63 binding partner, loss-of-function in multiple cell systems plus in vivo mouse model, mechanistic link through selective autophagy","pmids":["27869116"],"is_preprint":false},{"year":2020,"finding":"CCDC57 localizes to the proximal end of centrioles and directly interacts with CEP63. Loss of CCDC57 causes failure to localize CEP63 and CEP152 to the centrosome and results in centriole duplication defects. The centrosome-targeting region of CCDC57 is required for its interaction with CEP63 and for centriole duplication and cilium assembly functions.","method":"Proximity mapping (BioID), superresolution imaging, CCDC57 siRNA knockdown with CEP63/CEP152 localization readout, domain truncation analysis","journal":"Cell reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — proximity mapping plus superresolution imaging and domain truncation, single lab","pmids":["32402286"],"is_preprint":false},{"year":2020,"finding":"The CEP63•CEP152 complex undergoes liquid-liquid phase separation to form dynamic condensates at centrosomes. Two hydrophobic motifs, one from CEP63 and one from CEP152, are required for generating phase-separating condensates and high-molecular-weight assemblies. Treatment with 1,6-hexanediol (a phase separation disruptor) diminished endogenous CEP63 and CEP152 localization to centrosomes. In vitro, purified CEP63•CEP152 complex forms cylindrical structures or vesicle-like hollow spheres depending on spatial context.","method":"FRAP, in vitro reconstitution of purified complex, 1,6-hexanediol treatment, hydrophobic motif mutagenesis, 3D-SIM superresolution microscopy, macromolecular crowding assay","journal":"Cell cycle (Georgetown, Tex.)","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro reconstitution with purified proteins, mutagenesis of hydrophobic motifs, FRAP, and pharmacological perturbation; single lab but multiple orthogonal methods","pmids":["33208041"],"is_preprint":false},{"year":2022,"finding":"The APC/C localizes to centrosomes during mitosis in a CEP152-dependent manner and ubiquitylates CEP152, which releases CEP57 from the inhibitory CEP152-CEP63-CEP57 complex. Freed CEP57 then interacts with pericentrin to promote microtubule nucleation and spindle assembly.","method":"Co-immunoprecipitation of APC/C with centrosomal proteins, ubiquitylation assays, epistasis analysis of CEP57-pericentrin interaction after CEP152 degradation","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP, ubiquitylation assay, and functional epistasis; single lab","pmids":["34878135"],"is_preprint":false},{"year":2022,"finding":"CEP63 stabilizes the RNA-binding protein FXR1 by binding it and inhibiting its K63-ubiquitylation-dependent degradation. This stabilization promotes YAP1 expression and cancer stem-like properties in colorectal cancer cells. The KH domain of FXR1 is required for the CEP63-FXR1 interaction. USP36 was identified as a deubiquitinase that stabilizes CEP63 by reducing its K48-linked ubiquitination.","method":"Co-immunoprecipitation, ubiquitylation assays, domain mapping (FXR1 KH domain), in vitro and in vivo tumor growth assays, CEP63 overexpression/knockdown","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP with domain mapping, ubiquitylation assays, single lab with multiple orthogonal methods","pmids":["35989368"],"is_preprint":false},{"year":2025,"finding":"CEP152, CEP63, and PCNT form aggregates that function as cartwheel seeds (CS) for centriole assembly, operating independently of pre-existing centrioles. These seeds form in interphase as nanoscale concentric rings comprising CEP152 and CEP63 from which the cartwheel grows. ALMS1 interacts with CEP152, CEP63, and PCNT and is required for CS assembly and disassembly; depleting ALMS1 abolishes CS assembly and eliminates centrioles, while reintroducing ALMS1 generates de novo centrioles.","method":"ALMS1 co-immunoprecipitation with CEP152/CEP63/PCNT, ALMS1 depletion/re-expression with centriole biogenesis readout, disease-linked ALMS1 mutations, superresolution imaging of cartwheel seeds","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP identifying complex members, loss-of-function and rescue with defined centriole phenotype, superresolution imaging; preprint, not yet peer-reviewed","pmids":["40667363"],"is_preprint":true}],"current_model":"CEP63 is a centrosomal scaffold protein that localizes to the proximal end of centrioles as part of a CEP57-CEP63-CEP152 ring complex; it recruits PLK4 via CEP152 to promote mother-centriole-dependent centriole duplication, recruits CDK1 to regulate mitotic entry, undergoes liquid-liquid phase separation with CEP152 to concentrate at the centrosome, is phosphorylated by ATM/ATR on Ser 560 to delocalize from centrosomes and inhibit spindle assembly after DNA damage, is degraded by selective autophagy via p62 to control centrosome number, and—outside the centrosome—stabilizes the RNA-binding protein FXR1 by blocking its ubiquitin-dependent degradation."},"narrative":{"mechanistic_narrative":"CEP63 is a centrosomal scaffold protein that controls centriole duplication and mitotic fidelity by organizing the proximal end of centrioles within a CEP57–CEP63–CEP152 ring complex [PMID:23333316]. Through direct binding to CEP152 it recruits PLK4 to drive mother-centriole-dependent centriole biogenesis; its paralogue DEUP1 uses the same CEP152-binding mechanism to assemble deuterosomes for de novo centriole production during multiciliogenesis [PMID:24240477]. CEP63 also binds and recruits CDK1 to centrosomes to regulate mitotic entry, with its loss causing polyploidy and its overexpression driving centrosome amplification [PMID:21406398]. Localization of CEP63 and CEP152 to the centrosome is sustained by liquid–liquid phase separation of the CEP63·CEP152 complex, driven by hydrophobic motifs in each protein [PMID:33208041], and CEP63 centrosomal recruitment depends on the upstream proximal-end protein CCDC57 [PMID:32402286]. The DNA-damage kinases ATM and ATR phosphorylate CEP63 on Ser560, delocalizing it from the centrosome to inhibit spindle assembly [PMID:19182792], while selective autophagy degrades CEP63 via the receptor p62 to limit centrosome number [PMID:27869116]. Consistent with these roles, loss of CEP63 in mice produces microcephaly through p53-dependent apoptosis of neural progenitors driven by mitotic errors, as well as meiotic defects and male infertility [PMID:26158450]. Outside the centrosome, CEP63 stabilizes the RNA-binding protein FXR1 by blocking its K63-ubiquitylation-dependent degradation, promoting YAP1 expression and cancer stem-like properties [PMID:35989368].","teleology":[{"year":2009,"claim":"Established CEP63 as a node linking DNA-damage signaling to centrosome-driven spindle control, answering how DSBs restrain mitotic spindle assembly.","evidence":"cDNA library screen for ATM/ATR substrates, Xenopus egg extract spindle assembly with S560A mutagenesis, and CEP63 knockout in DT40 cells","pmids":["19182792"],"confidence":"High","gaps":["Does not define the structural basis of Ser560-dependent delocalization","Does not identify which centrosomal partners are lost upon phosphorylation"]},{"year":2011,"claim":"Showed CEP63 recruits CDK1 to centrosomes to govern mitotic entry, connecting the scaffold to cell-cycle progression and ploidy control.","evidence":"Reciprocal Co-IP, RNAi depletion with polyploidy/mitotic-skipping readout, and overexpression with roscovitine rescue in U2OS cells","pmids":["21406398"],"confidence":"Medium","gaps":["Direct vs. indirect CDK1 binding not resolved","Single lab without orthogonal interaction validation"]},{"year":2013,"claim":"Defined the core mechanism of centriole duplication: CEP63 binds CEP152 to recruit PLK4, with the same module repurposed for deuterosome-based biogenesis.","evidence":"Reciprocal Co-IP, RNAi in multiciliated cell differentiation, phylogenetic analysis, and functional rescue","pmids":["24240477"],"confidence":"High","gaps":["Stoichiometry of the CEP63-CEP152-PLK4 assembly not defined","Does not establish how PLK4 activity is spatially restricted"]},{"year":2013,"claim":"Placed CEP63 architecturally within a CEP57-CEP63-CEP152 ring at the proximal centriole end, providing the spatial framework for its scaffolding role.","evidence":"Selective chemical crosslinking and superresolution microscopy across 31 centrosomal proteins","pmids":["23333316"],"confidence":"Medium","gaps":["Ring geometry inferred from crosslinking distances, not atomic structure","Single lab"]},{"year":2015,"claim":"Demonstrated the organismal consequence of CEP63 loss—microcephaly via p53-dependent neural progenitor apoptosis—and distinguished mitotic-error causation from a DNA-damage-response mechanism.","evidence":"Cep63 knockout mouse with p53 double-knockout epistasis, centrosome/chromosome immunofluorescence, and meiotic spread analysis","pmids":["26158450"],"confidence":"High","gaps":["Does not pinpoint the molecular trigger of mitotic errors in progenitors","Mechanism of telomere clustering failure in meiosis unresolved"]},{"year":2016,"claim":"Identified selective autophagy as a degradative route controlling CEP63 abundance and thereby centrosome number, adding a turnover axis to its regulation.","evidence":"Autophagy-deficient and p62-/- cells, CEP63-p62 Co-IP, autophagosome co-localization, and overexpression phenotype","pmids":["27869116"],"confidence":"High","gaps":["E3 ligase ubiquitylating CEP63 for p62 recognition not identified","Trigger that signals CEP63 for autophagic turnover unknown"]},{"year":2020,"claim":"Identified CCDC57 as an upstream proximal-end factor required to localize CEP63 and CEP152 to centrosomes, defining a recruitment hierarchy.","evidence":"BioID proximity mapping, superresolution imaging, CCDC57 siRNA with CEP63/CEP152 localization readout, and domain truncation","pmids":["32402286"],"confidence":"Medium","gaps":["Whether CCDC57-CEP63 binding is direct vs. mediated not fully resolved","Single lab"]},{"year":2020,"claim":"Revealed that CEP63·CEP152 form phase-separated condensates, explaining how the scaffold concentrates at and maintains centrosomal localization.","evidence":"FRAP, in vitro reconstitution of purified complex, 1,6-hexanediol treatment, hydrophobic-motif mutagenesis, and 3D-SIM","pmids":["33208041"],"confidence":"High","gaps":["Physiological regulation of condensate formation in cells not established","Relationship between in vitro cylindrical/hollow structures and centriole architecture unclear"]},{"year":2022,"claim":"Showed APC/C-mediated ubiquitylation of CEP152 dismantles the inhibitory CEP152-CEP63-CEP57 complex to liberate CEP57 for spindle assembly, integrating CEP63 into mitotic ubiquitin signaling.","evidence":"Co-IP of APC/C with centrosomal proteins, ubiquitylation assays, and epistasis of CEP57-pericentrin interaction","pmids":["34878135"],"confidence":"Medium","gaps":["Direct role of CEP63 in this release step not isolated","Single lab"]},{"year":2022,"claim":"Uncovered a non-centrosomal function: CEP63 stabilizes FXR1 by blocking its K63-ubiquitylation-dependent degradation, linking CEP63 to YAP1-driven cancer stem-like properties.","evidence":"Co-IP, ubiquitylation assays, FXR1 KH-domain mapping, USP36-CEP63 stabilization, and tumor growth assays","pmids":["35989368"],"confidence":"Medium","gaps":["Whether this function requires centrosomal CEP63 or a separate pool is unknown","Single lab"]},{"year":2025,"claim":"Proposed that CEP152-CEP63-PCNT aggregates act as ALMS1-dependent cartwheel seeds enabling de novo centriole assembly independent of pre-existing centrioles.","evidence":"ALMS1 Co-IP with CEP152/CEP63/PCNT, depletion/re-expression with centriole readout, and superresolution imaging (preprint)","pmids":["40667363"],"confidence":"Medium","gaps":["Preprint, not yet peer-reviewed","How seeds template cartwheel symmetry mechanistically unresolved"]},{"year":null,"claim":"How CEP63's distinct activities—centriole duplication scaffold, mitotic-entry regulator, DNA-damage-responsive sensor, autophagy substrate, and FXR1 stabilizer—are coordinated within a cell remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structural model integrating CEP63's binding interfaces","Direct E3 ligase for CEP63 turnover unidentified","Spatial separation of centrosomal vs. FXR1-stabilizing pools undefined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[2,3,6]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[9]}],"localization":[{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[3,6,7]}],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[1,2,8]},{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[2,10]},{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[5]}],"complexes":["CEP57-CEP63-CEP152 ring complex"],"partners":["CEP152","CEP57","CDK1","PLK4","CCDC57","SQSTM1","FXR1","PCNT"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q96MT8","full_name":"Centrosomal protein of 63 kDa","aliases":[],"length_aa":703,"mass_kda":81.3,"function":"Required for normal spindle assembly (PubMed:21406398, PubMed:21983783, PubMed:26297806, PubMed:35793002). Plays a key role in mother-centriole-dependent centriole duplication; the function seems also to involve CEP152, CDK5RAP2 and WDR62 through a stepwise assembled complex at the centrosome that recruits CDK2 required for centriole duplication (PubMed:21983783, PubMed:26297806). Reported to be required for centrosomal recruitment of CEP152; however, this function has been questioned (PubMed:21983783, PubMed:26297806). Also recruits CDK1 to centrosomes (PubMed:21406398). Plays a role in DNA damage response (PubMed:21406398). Following DNA damage, such as double-strand breaks (DSBs), is removed from centrosomes; this leads to the inactivation of spindle assembly and delay in mitotic progression (PubMed:21406398). Promotes stabilization of FXR1 protein by inhibiting FXR1 ubiquitination (PubMed:35989368)","subcellular_location":"Cytoplasm, cytoskeleton, microtubule organizing center, centrosome; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriolar satellite","url":"https://www.uniprot.org/uniprotkb/Q96MT8/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CEP63","classification":"Not Classified","n_dependent_lines":8,"n_total_lines":1208,"dependency_fraction":0.006622516556291391},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/CEP63","total_profiled":1310},"omim":[{"mim_id":"621412","title":"CENTROSOMAL PROTEIN 57-LIKE 1; CEP57L1","url":"https://www.omim.org/entry/621412"},{"mim_id":"617936","title":"BUTYRYLCHOLINESTERASE DEFICIENCY; BCHED","url":"https://www.omim.org/entry/617936"},{"mim_id":"617148","title":"DEUTEROSOME ASSEMBLY PROTEIN 1; DEUP1","url":"https://www.omim.org/entry/617148"},{"mim_id":"617147","title":"COILED-COIL DOMAIN-CONTAINING PROTEIN 14; CCDC14","url":"https://www.omim.org/entry/617147"},{"mim_id":"617112","title":"KIAA0753 GENE; KIAA0753","url":"https://www.omim.org/entry/617112"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Centrosome","reliability":"Supported"},{"location":"Basal body","reliability":"Supported"},{"location":"Nucleoplasm","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/CEP63"},"hgnc":{"alias_symbol":["FLJ13386"],"prev_symbol":[]},"alphafold":{"accession":"Q96MT8","domains":[],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96MT8","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q96MT8-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q96MT8-F1-predicted_aligned_error_v6.png","plddt_mean":77.31},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CEP63","jax_strain_url":"https://www.jax.org/strain/search?query=CEP63"},"sequence":{"accession":"Q96MT8","fasta_url":"https://rest.uniprot.org/uniprotkb/Q96MT8.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q96MT8/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96MT8"}},"corpus_meta":[{"pmid":"24240477","id":"PMC_24240477","title":"The Cep63 paralogue Deup1 enables massive de novo centriole biogenesis for vertebrate multiciliogenesis.","date":"2013","source":"Nature cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/24240477","citation_count":168,"is_preprint":false},{"pmid":"23333316","id":"PMC_23333316","title":"Selective chemical crosslinking reveals a Cep57-Cep63-Cep152 centrosomal complex.","date":"2013","source":"Current biology : CB","url":"https://pubmed.ncbi.nlm.nih.gov/23333316","citation_count":100,"is_preprint":false},{"pmid":"26158450","id":"PMC_26158450","title":"CEP63 deficiency promotes p53-dependent microcephaly and reveals a role for the centrosome in meiotic recombination.","date":"2015","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/26158450","citation_count":87,"is_preprint":false},{"pmid":"19182792","id":"PMC_19182792","title":"An ATM- and ATR-dependent checkpoint inactivates spindle assembly by targeting CEP63.","date":"2009","source":"Nature cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/19182792","citation_count":58,"is_preprint":false},{"pmid":"21406398","id":"PMC_21406398","title":"Cep63 recruits Cdk1 to the centrosome: implications for regulation of mitotic entry, centrosome amplification, and genome maintenance.","date":"2011","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/21406398","citation_count":51,"is_preprint":false},{"pmid":"22555018","id":"PMC_22555018","title":"Computational investigation of pathogenic nsSNPs in CEP63 protein.","date":"2012","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/22555018","citation_count":47,"is_preprint":false},{"pmid":"27869116","id":"PMC_27869116","title":"Autophagy controls centrosome number by degrading Cep63.","date":"2016","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/27869116","citation_count":28,"is_preprint":false},{"pmid":"32402286","id":"PMC_32402286","title":"CCDC57 Cooperates with Microtubules and Microcephaly Protein CEP63 and Regulates Centriole Duplication and Mitotic Progression.","date":"2020","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/32402286","citation_count":21,"is_preprint":false},{"pmid":"26400686","id":"PMC_26400686","title":"Mutation in CEP63 co-segregating with developmental dyslexia in a Swedish family.","date":"2015","source":"Human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/26400686","citation_count":21,"is_preprint":false},{"pmid":"16410684","id":"PMC_16410684","title":"The transcripts of SFRP1,CEP63 and EIF4G2 genes are frequently downregulated in transitional cell carcinomas of the bladder.","date":"2006","source":"Oncology","url":"https://pubmed.ncbi.nlm.nih.gov/16410684","citation_count":21,"is_preprint":false},{"pmid":"33208041","id":"PMC_33208041","title":"Phase separation of the Cep63•Cep152 complex underlies the formation of dynamic supramolecular self-assemblies at human centrosomes.","date":"2020","source":"Cell cycle (Georgetown, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/33208041","citation_count":19,"is_preprint":false},{"pmid":"34878135","id":"PMC_34878135","title":"The APC/C targets the Cep152-Cep63 complex at the centrosome to regulate mitotic spindle assembly.","date":"2022","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/34878135","citation_count":13,"is_preprint":false},{"pmid":"35989368","id":"PMC_35989368","title":"CEP63 upregulates YAP1 to promote colorectal cancer progression through stabilizing RNA binding protein FXR1.","date":"2022","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/35989368","citation_count":9,"is_preprint":false},{"pmid":"34068194","id":"PMC_34068194","title":"Modifier Genes in Microcephaly: A Report on WDR62, CEP63, RAD50 and PCNT Variants Exacerbating Disease Caused by Biallelic Mutations of ASPM and CENPJ.","date":"2021","source":"Genes","url":"https://pubmed.ncbi.nlm.nih.gov/34068194","citation_count":9,"is_preprint":false},{"pmid":"34296302","id":"PMC_34296302","title":"Cep63 knockout inhibits the malignant phenotypes of papillary thyroid cancer cell line TPC‑1.","date":"2021","source":"Oncology reports","url":"https://pubmed.ncbi.nlm.nih.gov/34296302","citation_count":3,"is_preprint":false},{"pmid":"34156311","id":"PMC_34156311","title":"Polymorphism in miRNA target sites of CEP-63 and CEP-152 ring complex influences expression of CEP genes and favors tumorigenesis in glioma.","date":"2021","source":"Future oncology (London, England)","url":"https://pubmed.ncbi.nlm.nih.gov/34156311","citation_count":2,"is_preprint":false},{"pmid":"33472304","id":"PMC_33472304","title":"[Study on Cep63 expression and apoptosis of thyroid papillary carcinoma cell lines TPC-1].","date":"2021","source":"Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery","url":"https://pubmed.ncbi.nlm.nih.gov/33472304","citation_count":0,"is_preprint":false},{"pmid":"40667363","id":"PMC_40667363","title":"Centriole biogenesis is seeded by CEP152-CEP63-PCNT aggregates propagating outside the centriole through the Alström syndrome protein ALMS1.","date":"2025","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/40667363","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.05.21.655339","title":"The study of differential expressions of MCPH and Seckel syndrome genes and their paralogues","date":"2025-05-27","source":"bioRxiv","url":"https://doi.org/10.1101/2025.05.21.655339","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.06.26.661604","title":"Adaptable centriole biogenesis via the intrinsically disordered protein ALMS1","date":"2025-06-27","source":"bioRxiv","url":"https://doi.org/10.1101/2025.06.26.661604","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":11776,"output_tokens":3102,"usd":0.040929,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10533,"output_tokens":3754,"usd":0.073258,"stage2_stop_reason":"end_turn"},"total_usd":0.114187,"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\": \"ATM and ATR phosphorylate Xenopus CEP63 (XCEP63) on Ser 560 following DNA double-strand breaks, promoting its delocalization from the centrosome and thereby inhibiting centrosome-driven spindle assembly. Mutation of XCEP63 Ser 560 to Ala prevented spindle assembly defects, and CEP63 gene inactivation in DT40 cells impaired spindle assembly and prevented ATM/ATR-dependent mitotic effects.\",\n      \"method\": \"In vitro Xenopus egg extract spindle assembly assay, site-directed mutagenesis (S560A), cDNA expression library screen for ATM/ATR substrates, CEP63 gene knockout in avian DT40 cells\",\n      \"journal\": \"Nature cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — reconstitution in Xenopus extract, active-site mutagenesis, and genetic knockout with defined phenotype across multiple systems\",\n      \"pmids\": [\"19182792\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Human CEP63 binds to and recruits CDK1 to centrosomes, regulating mitotic entry. RNAi-mediated CEP63 depletion in U2OS cells caused polyploidization through mitotic skipping associated with loss of centrosomal CDK1. CEP63 overexpression induced de novo centrosome amplification during interphase, suppressible by the CDK inhibitor roscovitine.\",\n      \"method\": \"Co-immunoprecipitation, RNAi knockdown with cell cycle phenotype readout (polyploidy, mitotic skipping), overexpression with CDK inhibitor rescue\",\n      \"journal\": \"Cancer research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP plus loss-of-function and gain-of-function with pharmacological rescue, single lab\",\n      \"pmids\": [\"21406398\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"CEP63 regulates mother-centriole-dependent centriole duplication by binding to CEP152 and recruiting PLK4 to activate centriole biogenesis. Its paralogue DEUP1 (Cep63-derived) uses the same CEP152-binding mechanism to assemble deuterosomes for large-scale de novo centriole biogenesis in multiciliogenesis.\",\n      \"method\": \"Co-immunoprecipitation, RNAi knockdown in multiciliated cell differentiation assay, phylogenetic analysis, functional rescue experiments\",\n      \"journal\": \"Nature cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP for CEP63-CEP152-PLK4 interaction, loss-of-function with defined centriole duplication phenotype, replicated across multiple contexts\",\n      \"pmids\": [\"24240477\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"CEP57, CEP63, and CEP152 form a ring-like complex localizing around the proximal end of centrioles, as revealed by selective chemical crosslinking combined with superresolution microscopy.\",\n      \"method\": \"Selective chemical crosslinking, superresolution microscopy (STORM/PALM), proximity-based interaction mapping of 31 centrosomal proteins\",\n      \"journal\": \"Current biology : CB\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — chemical crosslinking with superresolution imaging, single lab but two orthogonal methods\",\n      \"pmids\": [\"23333316\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"CEP63-deficient mice develop microcephaly through p53-dependent apoptosis of neural progenitor cells triggered by centrosome-based mitotic errors (not aberrant DNA damage response). Brain size was rescued by p53 deletion. Additionally, CEP63 loss caused centrosome aberrations in spermatocytes, chromosome entanglements, and defective telomere clustering, leading to failed meiotic recombination and male infertility.\",\n      \"method\": \"Cep63 knockout mouse model, p53 double knockout epistasis, immunofluorescence of centrosome/chromosome defects, meiotic spread analysis\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic epistasis (p53 rescue of brain size), knockout mouse with defined cellular and organismal phenotypes, multiple orthogonal readouts\",\n      \"pmids\": [\"26158450\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Autophagy controls centrosome number by degrading CEP63. Autophagy-deficient cells accumulate extra centrosomes with multiple CEP63 dots. CEP63 is recruited to autophagosomes via interaction with p62 (a selective autophagy receptor). Upregulation of CEP63 increases centrosome number.\",\n      \"method\": \"Autophagy-deficient cell lines and p62-/- mouse hematopoietic cells, co-immunoprecipitation of CEP63 with p62, immunofluorescence of autophagosome-CEP63 co-localization, CEP63 overexpression phenotype\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — Co-IP identifying p62 as CEP63 binding partner, loss-of-function in multiple cell systems plus in vivo mouse model, mechanistic link through selective autophagy\",\n      \"pmids\": [\"27869116\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"CCDC57 localizes to the proximal end of centrioles and directly interacts with CEP63. Loss of CCDC57 causes failure to localize CEP63 and CEP152 to the centrosome and results in centriole duplication defects. The centrosome-targeting region of CCDC57 is required for its interaction with CEP63 and for centriole duplication and cilium assembly functions.\",\n      \"method\": \"Proximity mapping (BioID), superresolution imaging, CCDC57 siRNA knockdown with CEP63/CEP152 localization readout, domain truncation analysis\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — proximity mapping plus superresolution imaging and domain truncation, single lab\",\n      \"pmids\": [\"32402286\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"The CEP63•CEP152 complex undergoes liquid-liquid phase separation to form dynamic condensates at centrosomes. Two hydrophobic motifs, one from CEP63 and one from CEP152, are required for generating phase-separating condensates and high-molecular-weight assemblies. Treatment with 1,6-hexanediol (a phase separation disruptor) diminished endogenous CEP63 and CEP152 localization to centrosomes. In vitro, purified CEP63•CEP152 complex forms cylindrical structures or vesicle-like hollow spheres depending on spatial context.\",\n      \"method\": \"FRAP, in vitro reconstitution of purified complex, 1,6-hexanediol treatment, hydrophobic motif mutagenesis, 3D-SIM superresolution microscopy, macromolecular crowding assay\",\n      \"journal\": \"Cell cycle (Georgetown, Tex.)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro reconstitution with purified proteins, mutagenesis of hydrophobic motifs, FRAP, and pharmacological perturbation; single lab but multiple orthogonal methods\",\n      \"pmids\": [\"33208041\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"The APC/C localizes to centrosomes during mitosis in a CEP152-dependent manner and ubiquitylates CEP152, which releases CEP57 from the inhibitory CEP152-CEP63-CEP57 complex. Freed CEP57 then interacts with pericentrin to promote microtubule nucleation and spindle assembly.\",\n      \"method\": \"Co-immunoprecipitation of APC/C with centrosomal proteins, ubiquitylation assays, epistasis analysis of CEP57-pericentrin interaction after CEP152 degradation\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP, ubiquitylation assay, and functional epistasis; single lab\",\n      \"pmids\": [\"34878135\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"CEP63 stabilizes the RNA-binding protein FXR1 by binding it and inhibiting its K63-ubiquitylation-dependent degradation. This stabilization promotes YAP1 expression and cancer stem-like properties in colorectal cancer cells. The KH domain of FXR1 is required for the CEP63-FXR1 interaction. USP36 was identified as a deubiquitinase that stabilizes CEP63 by reducing its K48-linked ubiquitination.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitylation assays, domain mapping (FXR1 KH domain), in vitro and in vivo tumor growth assays, CEP63 overexpression/knockdown\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP with domain mapping, ubiquitylation assays, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"35989368\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CEP152, CEP63, and PCNT form aggregates that function as cartwheel seeds (CS) for centriole assembly, operating independently of pre-existing centrioles. These seeds form in interphase as nanoscale concentric rings comprising CEP152 and CEP63 from which the cartwheel grows. ALMS1 interacts with CEP152, CEP63, and PCNT and is required for CS assembly and disassembly; depleting ALMS1 abolishes CS assembly and eliminates centrioles, while reintroducing ALMS1 generates de novo centrioles.\",\n      \"method\": \"ALMS1 co-immunoprecipitation with CEP152/CEP63/PCNT, ALMS1 depletion/re-expression with centriole biogenesis readout, disease-linked ALMS1 mutations, superresolution imaging of cartwheel seeds\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP identifying complex members, loss-of-function and rescue with defined centriole phenotype, superresolution imaging; preprint, not yet peer-reviewed\",\n      \"pmids\": [\"40667363\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"CEP63 is a centrosomal scaffold protein that localizes to the proximal end of centrioles as part of a CEP57-CEP63-CEP152 ring complex; it recruits PLK4 via CEP152 to promote mother-centriole-dependent centriole duplication, recruits CDK1 to regulate mitotic entry, undergoes liquid-liquid phase separation with CEP152 to concentrate at the centrosome, is phosphorylated by ATM/ATR on Ser 560 to delocalize from centrosomes and inhibit spindle assembly after DNA damage, is degraded by selective autophagy via p62 to control centrosome number, and—outside the centrosome—stabilizes the RNA-binding protein FXR1 by blocking its ubiquitin-dependent degradation.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CEP63 is a centrosomal scaffold protein that controls centriole duplication and mitotic fidelity by organizing the proximal end of centrioles within a CEP57–CEP63–CEP152 ring complex [#3]. Through direct binding to CEP152 it recruits PLK4 to drive mother-centriole-dependent centriole biogenesis; its paralogue DEUP1 uses the same CEP152-binding mechanism to assemble deuterosomes for de novo centriole production during multiciliogenesis [#2]. CEP63 also binds and recruits CDK1 to centrosomes to regulate mitotic entry, with its loss causing polyploidy and its overexpression driving centrosome amplification [#1]. Localization of CEP63 and CEP152 to the centrosome is sustained by liquid–liquid phase separation of the CEP63·CEP152 complex, driven by hydrophobic motifs in each protein [#7], and CEP63 centrosomal recruitment depends on the upstream proximal-end protein CCDC57 [#6]. The DNA-damage kinases ATM and ATR phosphorylate CEP63 on Ser560, delocalizing it from the centrosome to inhibit spindle assembly [#0], while selective autophagy degrades CEP63 via the receptor p62 to limit centrosome number [#5]. Consistent with these roles, loss of CEP63 in mice produces microcephaly through p53-dependent apoptosis of neural progenitors driven by mitotic errors, as well as meiotic defects and male infertility [#4]. Outside the centrosome, CEP63 stabilizes the RNA-binding protein FXR1 by blocking its K63-ubiquitylation-dependent degradation, promoting YAP1 expression and cancer stem-like properties [#9].\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"Established CEP63 as a node linking DNA-damage signaling to centrosome-driven spindle control, answering how DSBs restrain mitotic spindle assembly.\",\n      \"evidence\": \"cDNA library screen for ATM/ATR substrates, Xenopus egg extract spindle assembly with S560A mutagenesis, and CEP63 knockout in DT40 cells\",\n      \"pmids\": [\"19182792\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not define the structural basis of Ser560-dependent delocalization\", \"Does not identify which centrosomal partners are lost upon phosphorylation\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Showed CEP63 recruits CDK1 to centrosomes to govern mitotic entry, connecting the scaffold to cell-cycle progression and ploidy control.\",\n      \"evidence\": \"Reciprocal Co-IP, RNAi depletion with polyploidy/mitotic-skipping readout, and overexpression with roscovitine rescue in U2OS cells\",\n      \"pmids\": [\"21406398\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct vs. indirect CDK1 binding not resolved\", \"Single lab without orthogonal interaction validation\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Defined the core mechanism of centriole duplication: CEP63 binds CEP152 to recruit PLK4, with the same module repurposed for deuterosome-based biogenesis.\",\n      \"evidence\": \"Reciprocal Co-IP, RNAi in multiciliated cell differentiation, phylogenetic analysis, and functional rescue\",\n      \"pmids\": [\"24240477\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Stoichiometry of the CEP63-CEP152-PLK4 assembly not defined\", \"Does not establish how PLK4 activity is spatially restricted\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Placed CEP63 architecturally within a CEP57-CEP63-CEP152 ring at the proximal centriole end, providing the spatial framework for its scaffolding role.\",\n      \"evidence\": \"Selective chemical crosslinking and superresolution microscopy across 31 centrosomal proteins\",\n      \"pmids\": [\"23333316\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Ring geometry inferred from crosslinking distances, not atomic structure\", \"Single lab\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Demonstrated the organismal consequence of CEP63 loss—microcephaly via p53-dependent neural progenitor apoptosis—and distinguished mitotic-error causation from a DNA-damage-response mechanism.\",\n      \"evidence\": \"Cep63 knockout mouse with p53 double-knockout epistasis, centrosome/chromosome immunofluorescence, and meiotic spread analysis\",\n      \"pmids\": [\"26158450\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not pinpoint the molecular trigger of mitotic errors in progenitors\", \"Mechanism of telomere clustering failure in meiosis unresolved\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Identified selective autophagy as a degradative route controlling CEP63 abundance and thereby centrosome number, adding a turnover axis to its regulation.\",\n      \"evidence\": \"Autophagy-deficient and p62-/- cells, CEP63-p62 Co-IP, autophagosome co-localization, and overexpression phenotype\",\n      \"pmids\": [\"27869116\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"E3 ligase ubiquitylating CEP63 for p62 recognition not identified\", \"Trigger that signals CEP63 for autophagic turnover unknown\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Identified CCDC57 as an upstream proximal-end factor required to localize CEP63 and CEP152 to centrosomes, defining a recruitment hierarchy.\",\n      \"evidence\": \"BioID proximity mapping, superresolution imaging, CCDC57 siRNA with CEP63/CEP152 localization readout, and domain truncation\",\n      \"pmids\": [\"32402286\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether CCDC57-CEP63 binding is direct vs. mediated not fully resolved\", \"Single lab\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Revealed that CEP63·CEP152 form phase-separated condensates, explaining how the scaffold concentrates at and maintains centrosomal localization.\",\n      \"evidence\": \"FRAP, in vitro reconstitution of purified complex, 1,6-hexanediol treatment, hydrophobic-motif mutagenesis, and 3D-SIM\",\n      \"pmids\": [\"33208041\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Physiological regulation of condensate formation in cells not established\", \"Relationship between in vitro cylindrical/hollow structures and centriole architecture unclear\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Showed APC/C-mediated ubiquitylation of CEP152 dismantles the inhibitory CEP152-CEP63-CEP57 complex to liberate CEP57 for spindle assembly, integrating CEP63 into mitotic ubiquitin signaling.\",\n      \"evidence\": \"Co-IP of APC/C with centrosomal proteins, ubiquitylation assays, and epistasis of CEP57-pericentrin interaction\",\n      \"pmids\": [\"34878135\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct role of CEP63 in this release step not isolated\", \"Single lab\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Uncovered a non-centrosomal function: CEP63 stabilizes FXR1 by blocking its K63-ubiquitylation-dependent degradation, linking CEP63 to YAP1-driven cancer stem-like properties.\",\n      \"evidence\": \"Co-IP, ubiquitylation assays, FXR1 KH-domain mapping, USP36-CEP63 stabilization, and tumor growth assays\",\n      \"pmids\": [\"35989368\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether this function requires centrosomal CEP63 or a separate pool is unknown\", \"Single lab\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Proposed that CEP152-CEP63-PCNT aggregates act as ALMS1-dependent cartwheel seeds enabling de novo centriole assembly independent of pre-existing centrioles.\",\n      \"evidence\": \"ALMS1 Co-IP with CEP152/CEP63/PCNT, depletion/re-expression with centriole readout, and superresolution imaging (preprint)\",\n      \"pmids\": [\"40667363\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Preprint, not yet peer-reviewed\", \"How seeds template cartwheel symmetry mechanistically unresolved\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How CEP63's distinct activities—centriole duplication scaffold, mitotic-entry regulator, DNA-damage-responsive sensor, autophagy substrate, and FXR1 stabilizer—are coordinated within a cell remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No structural model integrating CEP63's binding interfaces\", \"Direct E3 ligase for CEP63 turnover unidentified\", \"Spatial separation of centrosomal vs. FXR1-stabilizing pools undefined\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [2, 3, 6]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [9]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [3, 6, 7]},\n      {\"term_id\": \"GO:0005813\", \"supporting_discovery_ids\": [2, 3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [1, 2, 8]},\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [2, 10]},\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [5]}\n    ],\n    \"complexes\": [\n      \"CEP57-CEP63-CEP152 ring complex\"\n    ],\n    \"partners\": [\n      \"CEP152\",\n      \"CEP57\",\n      \"CDK1\",\n      \"PLK4\",\n      \"CCDC57\",\n      \"SQSTM1\",\n      \"FXR1\",\n      \"PCNT\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}