{"gene":"CEP97","run_date":"2026-06-09T22:57:18","timeline":{"discoveries":[{"year":2007,"finding":"CEP97 was purified as part of a complex with CP110 and directly recruits CP110 to centrosomes; depletion of CEP97 causes CP110 disappearance from centrosomes, spindle defects, and polyploidy. Loss of CEP97 or CP110 promotes primary cilia formation in cycling cells, and enforced CP110 expression suppresses cilia assembly in quiescent cells, establishing CEP97 and CP110 as collaborative inhibitors of ciliogenesis.","method":"Biochemical complex purification (Co-IP/MS), siRNA depletion, dominant-negative mutant expression, immunofluorescence","journal":"Cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal biochemical purification, siRNA depletion with multiple phenotypic readouts, dominant-negative expression, replicated by multiple subsequent labs","pmids":["17719545"],"is_preprint":false},{"year":2011,"finding":"Kif24, a kinesin-13 subfamily motor protein, specifically interacts with CP110 and CEP97 at centrosomes, preferentially localizes to mother centrioles, and is required for maintaining CP110 at mother centrioles in cycling cells. Kif24 can bind and depolymerize microtubules in vitro, and its ectopic expression specifically remodels centriolar microtubules.","method":"Co-immunoprecipitation, siRNA depletion, in vitro microtubule depolymerization assay, immunofluorescence","journal":"Cell","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — Co-IP, in vitro microtubule assay, siRNA depletion with defined phenotypes, published in high-impact journal with multiple orthogonal methods","pmids":["21620453"],"is_preprint":false},{"year":2012,"finding":"CEP104 interacts with CP110 and CEP97 at the centriole and is required for ciliogenesis, placing CEP104 in the CP110-CEP97 regulatory network at centrioles.","method":"Co-immunoprecipitation, siRNA depletion, immunofluorescence","journal":"Current biology : CB","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — Co-IP and functional depletion, single lab but two orthogonal methods","pmids":["22885064"],"is_preprint":false},{"year":2013,"finding":"MARK4 knockdown arrests the ciliogenesis program before complete removal of the CP110-CEP97 inhibitory complex from the mother centriole, placing MARK4 and ODF2 upstream of CP110-CEP97 removal in the ciliogenesis pathway.","method":"siRNA depletion, immunofluorescence, epistasis analysis","journal":"The Journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — epistasis/pathway placement by sequential knockdown, single lab","pmids":["23400999"],"is_preprint":false},{"year":2014,"finding":"TTBK2 kinase has the potential to phosphorylate CEP97 in vitro, and TTBK2 recruitment to the mother centriole (via Cep164 binding) is required for CP110 and CEP97 removal during ciliogenesis initiation.","method":"In vitro kinase assay, TTBK2 variant expression/rescue, siRNA depletion, immunofluorescence","journal":"Genes to cells : devoted to molecular & cellular mechanisms","confidence":"Medium","confidence_rationale":"Tier 1-2 / Moderate — in vitro kinase assay showing CEP97 phosphorylation by TTBK2, plus siRNA/rescue epistasis; single lab","pmids":["25297623"],"is_preprint":false},{"year":2015,"finding":"WDR8 and Cep135, proximal-end centriolar proteins, are required for unlocking the distal end of the mother centriole from the CP110-CEP97 inhibitory complex, placing them upstream of CP110-CEP97 removal in ciliogenesis.","method":"siRNA depletion, immunofluorescence, epistasis analysis","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — depletion with defined ciliogenesis phenotype and pathway placement relative to CP110-CEP97, single lab","pmids":["26675238"],"is_preprint":false},{"year":2015,"finding":"In cytotoxic T lymphocytes (CTLs), CP110 and CEP97 remain associated with the mother centriole during centrosome docking at the immunological synapse, and no axoneme or transition zone ciliary structures form, establishing that centrosome docking can occur without ciliogenesis when CP110-CEP97 is retained.","method":"High-resolution TEM tomography, immunofluorescence, siRNA depletion","journal":"Current biology : CB","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — TEM tomography and immunofluorescence with functional consequence; single lab","pmids":["26670998"],"is_preprint":false},{"year":2016,"finding":"Crystal structure of CEP104's TOG domain was solved, and biophysical characterization demonstrated direct interactions between CEP104 and CP110, CEP97, EB protein, and tubulin, mapping the interaction network at the centriole distal tip.","method":"X-ray crystallography, biophysical binding assays (ITC/SPR), sequence analysis","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Moderate — crystal structure plus biophysical quantification of direct binding; single lab with multiple orthogonal methods","pmids":["27402853"],"is_preprint":false},{"year":2016,"finding":"In Drosophila, Asterless (Asl, ortholog of Cep152) controls centriole length via the centriole protein Cep97; loss of Asl affects Cep97-dependent centriole length regulation in germline and somatic tissue.","method":"Genetic loss-of-function (Drosophila), immunofluorescence, phenotypic analysis of centriole length","journal":"The Journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis in Drosophila model organism, single lab","pmids":["27185836"],"is_preprint":false},{"year":2018,"finding":"MPP9 is recruited by KIF24 to the distal end of the mother centriole where it forms a ring-like structure and recruits the CP110-CEP97 complex by directly binding CEP97. Upon phosphorylation by TTBK2 at the onset of ciliogenesis, MPP9 is degraded via the ubiquitin-proteasome system, facilitating removal of CP110 and CEP97 from the mother centriole.","method":"Co-immunoprecipitation, super-resolution microscopy, siRNA depletion, ubiquitin-proteasome inhibitor treatment, mouse kidney analysis","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct binding shown by Co-IP, super-resolution localization, in vivo validation in mouse kidneys, multiple orthogonal methods","pmids":["30375385"],"is_preprint":false},{"year":2018,"finding":"LRRC45 depletion does not impair removal of CP110-CEP97 from the mother centriole, establishing LRRC45 acts downstream of CP110-CEP97 removal in ciliogenesis.","method":"siRNA depletion, immunofluorescence, epistasis analysis","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — negative epistasis finding (LRRC45 not required for CP110-CEP97 removal), siRNA with immunofluorescence; single lab","pmids":["30131441"],"is_preprint":false},{"year":2020,"finding":"In Drosophila, Cep97 is essential for formation of full-length centrioles in multiple tissues and interacts with the microtubule deacetylase Sirt2; both Sirt2 deletion and Atat1 (acetylase) deletion affect centriole size, supporting a model whereby Cep97 acts as a protective cap cooperating with the microtubule acetylation machinery to maintain centriole stability. Unlike in vertebrates, Drosophila Cep97 is only transiently removed from basal bodies and its loss strongly impairs ciliogenesis.","method":"Genetic loss-of-function (Drosophila), Co-immunoprecipitation/interaction screen, immunofluorescence, ultrastructural analysis","journal":"Current biology : CB","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic loss-of-function in multiple tissues, identification of Sirt2 as interactor, epistasis with acetylation machinery, multiple orthogonal methods","pmids":["32589908"],"is_preprint":false},{"year":2021,"finding":"CEP97 interacts with Dyrk1a kinase in Xenopus multiciliated cells; Dyrk1a phosphorylates CEP97, which promotes recruitment of Plk1, a critical regulator of centriole disengagement that cooperates with Separase for centriole separation during multiciliogenesis. Knockdown of either CEP97 or Dyrk1a disrupts cilia formation and centriole disengagement, rescued by Separase overexpression.","method":"Co-immunoprecipitation, in vitro kinase assay, morpholino knockdown in Xenopus, rescue experiments with Separase overexpression, immunofluorescence","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — in vitro kinase assay, Co-IP, in vivo knockdown with genetic rescue; multiple orthogonal methods in Xenopus model","pmids":["34787650"],"is_preprint":false},{"year":2021,"finding":"LUBAC-mediated linear ubiquitination of CP110 is required for CP110 removal from the mother centriole, with PRPF8 acting as a receptor for linear ubiquitin chains at the distal mother centriole. CEP97, as part of the CP110-CEP97 complex, is targeted by this LUBAC-dependent mechanism.","method":"Co-immunoprecipitation, ubiquitination assays, siRNA depletion, immunofluorescence","journal":"The Journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — biochemical ubiquitination assays and Co-IP, functional depletion; CEP97 implicated as part of complex but direct modification not shown for CEP97 itself","pmids":["34813648"],"is_preprint":false},{"year":2022,"finding":"In Drosophila embryos, CP110 and CEP97 form a complex at the distal end of centrioles whose levels oscillate as centriole MTs grow; altering CP110 or Cep97 levels perturbs the Plk4 oscillation and cartwheel growth at the proximal end, revealing crosstalk between distal-end cap proteins and proximal-end centriole growth machinery.","method":"Live imaging, genetic manipulation (CP110/Cep97 overexpression/depletion), quantitative fluorescence microscopy in Drosophila embryos","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — live imaging and genetic perturbation showing cross-talk, single lab, Drosophila model","pmids":["35707992"],"is_preprint":false},{"year":2022,"finding":"ENKD1 competes with CEP97 for binding to CP110; depletion of ENKD1 enhances the CP110-CEP97 interaction and detains CP110 at the mother centriole, blocking ciliogenesis. Simultaneous knockdown of ENKD1 and CP110 reverses the ciliogenesis defect, placing ENKD1 as a positive regulator of CP110 removal by competing with CEP97.","method":"Co-immunoprecipitation, competitive binding assay, siRNA depletion, double-knockdown epistasis, super-resolution microscopy, mouse knockout","journal":"EMBO reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — competitive binding shown by Co-IP, double-knockdown epistasis, in vivo mouse knockout, super-resolution microscopy; multiple orthogonal methods","pmids":["35301795"],"is_preprint":false},{"year":2022,"finding":"The CP110-CEP97-CEP290 centrosomal complex is required for seeding the initial phosphorylated HSP27 ring during aggresome assembly at the centrosome; limiting amounts of CP110 in senescent cells impairs aggresome formation and aggregation of mutant huntingtin.","method":"High-resolution quantitative microscopy, siRNA depletion, immunofluorescence, functional aggregation assays","journal":"Nature cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — quantitative imaging and functional depletion establishing CP110-CEP97-CEP290 complex requirement for aggresome seeding; single lab","pmids":["35411088"],"is_preprint":false},{"year":2022,"finding":"In C. elegans, homologs of Cep97 and Cep135/BLD10 are expressed in somatic tissues but not in early embryos, identified by proximity-labeling TurboID interactome mapping; their tissue-specific expression explains why these conserved centriolar components had not been previously identified in worm.","method":"TurboID proximity labeling, mass spectrometry, GFP-nanobody indirect proximity labeling in whole animal","journal":"PLoS genetics","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — proximity labeling MS identifies Cep97 homolog in somatic tissues; novel identification but no direct functional assay for Cep97 in worm","pmids":["35442950"],"is_preprint":false},{"year":2023,"finding":"PCM1 and centriolar satellites facilitate efficient removal of CP110 and CEP97 from the distal mother centriole during ciliogenesis initiation; Pcm1-null RPE1 cells show reduced docking of the mother centriole to the ciliary vesicle and impaired CP110 and CEP97 removal.","method":"Genetic knockout (mouse and human RPE1 cells), immunofluorescence, ciliogenesis assays","journal":"eLife","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic KO in both mouse and human cell lines with defined CP110-CEP97 removal phenotype; single lab","pmids":["36790165"],"is_preprint":false},{"year":2023,"finding":"In Drosophila, Cep97 is the central scaffolding unit required to recruit distal tip complex (DTC) components to the distal tip of centrioles; Cep104 and Cep97 cooperate during spermiogenesis to align spermatids and coordinate individualization.","method":"Proximity-labeling screen, genetic loss-of-function (Cep104 null flies), immunofluorescence, interactome mapping","journal":"Current biology : CB","confidence":"High","confidence_rationale":"Tier 2 / Strong — proximity-labeling interactome plus genetic null fly analysis with multiple phenotypic readouts; establishes Cep97 as central scaffold for DTC","pmids":["37729913"],"is_preprint":false},{"year":2024,"finding":"During cerebellar granule cell differentiation, CEP97 is recruited to docked mother centrioles in maturing neurons, capping them and preventing cilia regrowth, establishing a mechanism by which cilia are permanently lost in mature neurons.","method":"Single-cell transcriptomics, immunocytology, subcellular localization analysis across differentiation stages","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — localization tied to functional consequence (no cilia regrowth), single lab, correlative but with defined protein recruitment event","pmids":["39705308"],"is_preprint":false},{"year":2023,"finding":"miR-106b in morphine-stimulated astrocyte-derived extracellular vesicles targets CEP97, reducing CEP97 levels in recipient astrocytes to promote primary ciliogenesis; anti-miR-106b delivery restores CEP97 expression and inhibits ciliogenesis.","method":"miRNA targeting validation, anti-miR delivery, immunofluorescence, in vivo mouse morphine tolerance model","journal":"Molecular therapy : the journal of the American Society of Gene Therapy","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — miRNA-target relationship validated functionally with rescue, in vivo confirmation; single lab","pmids":["37012704"],"is_preprint":false},{"year":2026,"finding":"CDK1 phosphorylates centriolar proteins including Centrobin at the centrosome, and CEP97-CCP110 restricts Centrobin localization to centrioles; CDK1-dependent phosphorylation suppresses Centrobin's centriole elongation activity. CEP97-CCP110 and CDK1 cooperatively restrict centriole elongation by inhibiting Centrobin via distinct mechanisms. Removal of CEP97 during mouse development causes centriole overelongation, impaired ciliogenesis, attenuated Hedgehog signaling, and disrupted heart development.","method":"Centrosome-specific phosphoproteomics, CDK1 inhibition, CEP97 knockout mice, ciliogenesis assays, HH signaling readouts, immunofluorescence","journal":"Genes & development","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — centrosome-specific phosphoproteomics, genetic KO in mice with developmental phenotypes, multiple orthogonal methods demonstrating CEP97-CCP110 restricts Centrobin","pmids":["42140673"],"is_preprint":false},{"year":2026,"finding":"Expansion microscopy of Drosophila S2 cells reveals that Cep97 forms a ring structure at the distal tip of the centriole, clarifying its role as a cap on the growing centriole end.","method":"Expansion microscopy (ExM) of S2 cells and fly tissues","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct ultrastructural imaging with ExM revealing ring geometry; single lab, single method but high-resolution structural result","pmids":["41347334"],"is_preprint":false},{"year":2025,"finding":"CEP76 interacts with CCP110 and CEP97 (identified by proteomics), and CEP76 depletion impairs ciliogenesis; this places CEP76 in the CP110-CEP97 interaction network at the centrosome-cilium interface.","method":"Proximity proteomics, siRNA depletion, ciliary phenotype analysis in RPE1 cells","journal":"Science advances","confidence":"Low","confidence_rationale":"Tier 3 / Weak — proteomics identification of interaction, no direct functional dissection of CEP97-CEP76 relationship; single lab","pmids":["41105778"],"is_preprint":false},{"year":2025,"finding":"EHD1, through its membrane tubulation function, directly promotes CP110/CEP97 removal from the mother centriole cap during ciliogenesis progression, linking membrane tubule formation at the mother centriole to distal cap disassembly.","method":"3D isotropic EM ultrastructure imaging, siRNA depletion of EHD1, quantitative analysis of CP110/CEP97 removal","journal":"bioRxiv (preprint)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct ultrastructural imaging plus functional depletion linking membrane tubulation to CP110/CEP97 removal; preprint, single lab","pmids":["40894589"],"is_preprint":true}],"current_model":"CEP97 is a conserved centriolar distal-tip protein that forms a cap complex with CP110 (and CEP290/CEP104) at the distal end of centrioles to suppress ciliogenesis in cycling cells and restrict centriole elongation by limiting Centrobin activity; its removal from the mother centriole — orchestrated by upstream regulators including MPP9, TTBK2, ENKD1, Dyrk1a (which phosphorylates CEP97 to recruit Plk1/Separase), and membrane-tubulating EHD1 — is required for ciliogenesis initiation, while in Drosophila Cep97 additionally maintains centriole structural integrity in cooperation with the microtubule acetylation machinery (Sirt2/Atat1) and acts as the central scaffold recruiting the distal tip complex."},"narrative":{"mechanistic_narrative":"CEP97 is a conserved centriolar distal-tip protein that, together with CP110, forms a cap complex at the distal end of centrioles which suppresses ciliogenesis in cycling cells; CEP97 directly recruits CP110 to centrosomes, and loss of either protein triggers ectopic primary cilia formation while enforced CP110 suppresses cilia assembly in quiescent cells [PMID:17719545]. The CEP97-CP110 cap nucleates a broader distal-tip interaction network including the kinesin-13 motor KIF24, which is required to retain CP110 at the mother centriole, and CEP104, which bridges CP110, CEP97, EB protein and tubulin at the centriole tip [PMID:21620453, PMID:22885064, PMID:27402853]. Productive ciliogenesis requires the regulated removal of this cap from the mother centriole, a step controlled by an extensive upstream network: MPP9 forms a ring that recruits the complex by directly binding CEP97 and is degraded upon TTBK2 phosphorylation, ENKD1 competes with CEP97 for CP110 binding to drive CP110 release, and PCM1/centriolar satellites and LUBAC-mediated linear ubiquitination further facilitate cap disassembly [PMID:30375385, PMID:25297623, PMID:35301795, PMID:36790165, PMID:34813648]. CEP97 is itself a phosphorylation substrate: TTBK2 and Dyrk1a phosphorylate CEP97, with Dyrk1a-dependent phosphorylation promoting Plk1 recruitment to drive centriole disengagement during multiciliogenesis [PMID:25297623, PMID:34787650]. Beyond ciliary control, the CEP97-CP110 cap restricts centriole elongation by limiting Centrobin activity in cooperation with CDK1, and CEP97 loss in mice causes centriole overelongation, impaired ciliogenesis, attenuated Hedgehog signaling and disrupted heart development [PMID:42140673]. In Drosophila, Cep97 forms a distal-tip ring and acts as the central scaffold recruiting the distal tip complex, maintaining centriole structural integrity in cooperation with the microtubule acetylation machinery (Sirt2/Atat1) [PMID:32589908, PMID:37729913, PMID:41347334]. CEP97 levels also gate cell-type-specific cilia outcomes, capping docked mother centrioles to permanently prevent cilia regrowth in maturing neurons [PMID:39705308].","teleology":[{"year":2007,"claim":"Established CEP97 as the physical recruiter of CP110 to centrosomes and defined the CEP97-CP110 complex as a collaborative inhibitor of ciliogenesis, answering what molecular activity restrains cilia assembly in cycling cells.","evidence":"Co-IP/MS complex purification, siRNA depletion with spindle/ploidy and ciliogenesis readouts, dominant-negative expression","pmids":["17719545"],"confidence":"High","gaps":["Did not define how the complex is removed to permit ciliogenesis","No structural basis for CEP97-CP110 binding"]},{"year":2011,"claim":"Showed that the kinesin-13 KIF24 partners with CEP97-CP110 and is required to maintain CP110 at mother centrioles, linking the cap to centriolar microtubule remodeling.","evidence":"Co-IP, siRNA depletion, in vitro microtubule depolymerization assay","pmids":["21620453"],"confidence":"High","gaps":["Did not define how KIF24 microtubule activity is regulated","Role of CEP97 in KIF24 recruitment versus retention not separated"]},{"year":2012,"claim":"Added CEP104 to the CEP97-CP110 distal-tip network and tied it functionally to ciliogenesis.","evidence":"Co-IP, siRNA depletion, immunofluorescence","pmids":["22885064"],"confidence":"Medium","gaps":["Direct versus indirect CEP97-CEP104 binding not resolved at this stage","Single lab"]},{"year":2014,"claim":"Identified TTBK2 as a kinase that phosphorylates CEP97 and is required for CP110/CEP97 removal, providing a kinase trigger for cap disassembly at ciliogenesis onset.","evidence":"In vitro kinase assay, TTBK2 rescue/variant expression, siRNA depletion","pmids":["25297623"],"confidence":"Medium","gaps":["Phosphosites on CEP97 and their functional consequence not mapped","In vitro phosphorylation not confirmed at endogenous sites in vivo"]},{"year":2015,"claim":"Placed proximal-end factors WDR8/Cep135 upstream of CP110-CEP97 removal, showing that distal cap disassembly is gated by proximal centriolar signals.","evidence":"siRNA depletion, epistasis analysis, immunofluorescence","pmids":["26675238"],"confidence":"Medium","gaps":["Molecular link between proximal proteins and distal cap removal undefined","Single lab"]},{"year":2015,"claim":"Demonstrated that retention of CEP97-CP110 permits centrosome docking at the immunological synapse without ciliogenesis, dissociating docking from cilia formation.","evidence":"TEM tomography, immunofluorescence, siRNA depletion in CTLs","pmids":["26670998"],"confidence":"Medium","gaps":["Mechanism keeping the cap retained in CTLs not defined","Single lab"]},{"year":2016,"claim":"Provided structural and biophysical mapping of the distal-tip network, demonstrating CEP104 binds CEP97, CP110, EB protein and tubulin directly.","evidence":"X-ray crystallography of CEP104 TOG domain, ITC/SPR binding assays","pmids":["27402853"],"confidence":"High","gaps":["No structure of CEP97 itself","CEP97 binding interface not crystallized"]},{"year":2016,"claim":"Showed in Drosophila that Asterless/Cep152 controls centriole length via Cep97, implicating CEP97 in centriole elongation control.","evidence":"Drosophila genetic loss-of-function, immunofluorescence, centriole length phenotyping","pmids":["27185836"],"confidence":"Medium","gaps":["Mechanism by which Cep97 limits length not defined here","Conservation to vertebrate length control untested"]},{"year":2018,"claim":"Defined MPP9 as a direct CEP97 binder forming a recruiting ring, whose TTBK2-triggered proteasomal degradation enables cap removal, linking the kinase trigger to a degradation step.","evidence":"Co-IP, super-resolution microscopy, proteasome inhibition, mouse kidney analysis","pmids":["30375385"],"confidence":"High","gaps":["E3 ligase for MPP9 not identified","Whether CEP97 is itself degraded versus released unresolved"]},{"year":2018,"claim":"Ordered LRRC45 downstream of CP110-CEP97 removal by showing its depletion does not block cap removal, refining pathway architecture.","evidence":"siRNA depletion, immunofluorescence, epistasis","pmids":["30131441"],"confidence":"Medium","gaps":["Negative result does not place LRRC45's exact step","Single lab"]},{"year":2020,"claim":"Established a structural-integrity role for Drosophila Cep97 as a protective cap cooperating with the microtubule acetylation machinery, distinguishing the fly cap (only transiently removed) from vertebrates.","evidence":"Drosophila genetic loss-of-function in multiple tissues, interaction screen identifying Sirt2, ultrastructural analysis","pmids":["32589908"],"confidence":"High","gaps":["Whether vertebrate CEP97 has an analogous acetylation-linked role untested","Direct CEP97-Sirt2 binding interface not mapped"]},{"year":2021,"claim":"Showed that Dyrk1a phosphorylates CEP97 to recruit Plk1 and drive centriole disengagement during multiciliogenesis, connecting CEP97 phosphorylation to centriole separation machinery.","evidence":"Co-IP, in vitro kinase assay, morpholino knockdown and Separase rescue in Xenopus","pmids":["34787650"],"confidence":"High","gaps":["CEP97 phosphosites recognized by Plk1 docking not mapped","Relationship between Dyrk1a and TTBK2 phosphorylation of CEP97 unresolved"]},{"year":2021,"claim":"Implicated LUBAC-mediated linear ubiquitination and the PRPF8 ubiquitin receptor in removal of the CP110-CEP97 cap, adding a ubiquitin-based disassembly route.","evidence":"Co-IP, ubiquitination assays, siRNA depletion, immunofluorescence","pmids":["34813648"],"confidence":"Medium","gaps":["Direct ubiquitination of CEP97 itself not demonstrated","How linear ubiquitin drives physical removal unresolved"]},{"year":2022,"claim":"Revealed crosstalk in Drosophila embryos between the distal CP110-Cep97 cap and proximal Plk4-driven cartwheel growth, showing cap levels feed back on centriole biogenesis.","evidence":"Live imaging, genetic perturbation, quantitative fluorescence in Drosophila embryos","pmids":["35707992"],"confidence":"Medium","gaps":["Molecular mediator of distal-to-proximal crosstalk unknown","Single lab"]},{"year":2022,"claim":"Identified ENKD1 as a competitor with CEP97 for CP110 binding that promotes CP110 release, defining a competition mechanism for cap disassembly.","evidence":"Co-IP, competitive binding assay, double-knockdown epistasis, super-resolution microscopy, mouse knockout","pmids":["35301795"],"confidence":"High","gaps":["How ENKD1 access to CP110 is timed during ciliogenesis unclear","Effect on CEP97 retention versus CP110 retention not fully separated"]},{"year":2022,"claim":"Extended CEP97-CP110 function beyond cilia by showing the CP110-CEP97-CEP290 complex seeds aggresome assembly via a phospho-HSP27 ring at the centrosome.","evidence":"Quantitative microscopy, siRNA depletion, aggregation assays","pmids":["35411088"],"confidence":"Medium","gaps":["Direct role of CEP97 versus CP110/CEP290 in seeding not dissected","Single lab"]},{"year":2022,"claim":"Mapped a Cep97 homolog to somatic tissues in C. elegans by interactome profiling, explaining its prior absence from worm studies.","evidence":"TurboID proximity labeling, mass spectrometry in whole animal","pmids":["35442950"],"confidence":"Medium","gaps":["No direct functional assay for worm Cep97","Tissue-specific function untested"]},{"year":2023,"claim":"Showed PCM1/centriolar satellites facilitate efficient CP110-CEP97 removal and mother-centriole docking to the ciliary vesicle.","evidence":"Mouse and human RPE1 knockouts, ciliogenesis assays, immunofluorescence","pmids":["36790165"],"confidence":"Medium","gaps":["Whether satellites act on the cap directly or via cargo delivery unresolved","Single lab"]},{"year":2023,"claim":"Established Drosophila Cep97 as the central scaffolding subunit recruiting the distal tip complex, and defined a Cep97-Cep104 role in spermiogenesis.","evidence":"Proximity-labeling interactome, Cep104-null fly genetics, immunofluorescence","pmids":["37729913"],"confidence":"High","gaps":["Whether vertebrate CEP97 is the equivalent DTC scaffold untested","DTC assembly order not fully defined"]},{"year":2023,"claim":"Demonstrated a regulatory input where miR-106b in morphine-stimulated EVs targets CEP97 to lower its levels and de-repress ciliogenesis in astrocytes.","evidence":"miRNA target validation, anti-miR rescue, in vivo mouse morphine model, immunofluorescence","pmids":["37012704"],"confidence":"Medium","gaps":["Other CEP97 mRNA regulators not surveyed","Single lab"]},{"year":2024,"claim":"Showed CEP97 is recruited to docked mother centrioles in maturing cerebellar neurons to cap them and permanently prevent cilia regrowth, defining a developmental cilia-loss mechanism.","evidence":"Single-cell transcriptomics, immunocytology, localization across differentiation","pmids":["39705308"],"confidence":"Medium","gaps":["Trigger for CEP97 recruitment in maturing neurons unknown","Correlative localization, no perturbation of CEP97 in neurons"]},{"year":2026,"claim":"Established that CEP97-CP110 restricts centriole elongation by limiting Centrobin in cooperation with CDK1, and that CEP97 loss in mice causes overelongation, ciliogenesis defects, attenuated Hedgehog signaling and heart defects, linking CEP97 to development.","evidence":"Centrosome-specific phosphoproteomics, CDK1 inhibition, CEP97 knockout mice, HH and ciliogenesis readouts","pmids":["42140673"],"confidence":"High","gaps":["Direct CEP97-Centrobin interaction not detailed","Mechanism distinguishing CEP97-CP110 from CDK1 inhibition of Centrobin not fully resolved"]},{"year":2026,"claim":"Resolved Cep97 as a ring structure at the distal tip in Drosophila by expansion microscopy, clarifying its geometry as a cap on the growing centriole end.","evidence":"Expansion microscopy of S2 cells and fly tissues","pmids":["41347334"],"confidence":"Medium","gaps":["Ring geometry not confirmed for vertebrate CEP97","Molecular organization within the ring not resolved"]},{"year":null,"claim":"How CEP97 itself is physically displaced and turned over during cap removal — versus its partner CP110 — and the molecular interface CEP97 uses to bind CP110 remain unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No high-resolution structure of CEP97 or its CP110-binding interface","Whether CEP97 is degraded, released, or sequestered during cap removal not established","Functional phosphosites on CEP97 not mapped"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,9,19]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0,15,22]}],"localization":[{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[0,1,9,23]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[1,7]}],"pathway":[{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[0,9,22]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[22,20]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[22]}],"complexes":["CP110-CEP97 distal-tip cap complex","CP110-CEP97-CEP290 complex","centriole distal tip complex (DTC)"],"partners":["CP110","KIF24","CEP104","MPP9","ENKD1","TTBK2","DYRK1A","SIRT2"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q8IW35","full_name":"Centrosomal protein of 97 kDa","aliases":["Leucine-rich repeat and IQ domain-containing protein 2"],"length_aa":865,"mass_kda":97.0,"function":"Acts as a key negative regulator of ciliogenesis in collaboration with CCP110 by capping the mother centriole thereby preventing cilia formation (PubMed:17719545, PubMed:30375385). Required for recruitment of CCP110 to the centrosome (PubMed:17719545)","subcellular_location":"Cytoplasm, cytoskeleton, microtubule organizing center, centrosome; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole","url":"https://www.uniprot.org/uniprotkb/Q8IW35/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CEP97","classification":"Not Classified","n_dependent_lines":340,"n_total_lines":1208,"dependency_fraction":0.2814569536423841},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"CALM1","stoichiometry":0.2},{"gene":"CALM3","stoichiometry":0.2},{"gene":"TUBA1B","stoichiometry":0.2},{"gene":"TUBB4B","stoichiometry":0.2},{"gene":"VPS35","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/CEP97","total_profiled":1310},"omim":[{"mim_id":"621119","title":"ENKURIN DOMAIN-CONTAINING PROTEIN 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all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/CEP97"},"hgnc":{"alias_symbol":["FLJ23047"],"prev_symbol":["LRRIQ2"]},"alphafold":{"accession":"Q8IW35","domains":[{"cath_id":"1.20.5","chopping":"576-636","consensus_level":"medium","plddt":86.3105,"start":576,"end":636}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8IW35","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8IW35-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8IW35-F1-predicted_aligned_error_v6.png","plddt_mean":58.19},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CEP97","jax_strain_url":"https://www.jax.org/strain/search?query=CEP97"},"sequence":{"accession":"Q8IW35","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8IW35.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8IW35/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8IW35"}},"corpus_meta":[{"pmid":"17719545","id":"PMC_17719545","title":"Cep97 and CP110 suppress a 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TurboID approach identifies tissue-specific centriolar components in C. elegans.","date":"2022","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/35442950","citation_count":27,"is_preprint":false},{"pmid":"35301795","id":"PMC_35301795","title":"ENKD1 promotes CP110 removal through competing with CEP97 to initiate ciliogenesis.","date":"2022","source":"EMBO reports","url":"https://pubmed.ncbi.nlm.nih.gov/35301795","citation_count":26,"is_preprint":false},{"pmid":"34813648","id":"PMC_34813648","title":"LUBAC regulates ciliogenesis by promoting CP110 removal from the mother centriole.","date":"2021","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/34813648","citation_count":21,"is_preprint":false},{"pmid":"37012704","id":"PMC_37012704","title":"Extracellular vesicle-mediated delivery of anti-miR-106b inhibits morphine-induced primary ciliogenesis in the brain.","date":"2023","source":"Molecular therapy : the journal of the American Society of 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Loss of CEP97 or CP110 promotes primary cilia formation in cycling cells, and enforced CP110 expression suppresses cilia assembly in quiescent cells, establishing CEP97 and CP110 as collaborative inhibitors of ciliogenesis.\",\n      \"method\": \"Biochemical complex purification (Co-IP/MS), siRNA depletion, dominant-negative mutant expression, immunofluorescence\",\n      \"journal\": \"Cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal biochemical purification, siRNA depletion with multiple phenotypic readouts, dominant-negative expression, replicated by multiple subsequent labs\",\n      \"pmids\": [\"17719545\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Kif24, a kinesin-13 subfamily motor protein, specifically interacts with CP110 and CEP97 at centrosomes, preferentially localizes to mother centrioles, and is required for maintaining CP110 at mother centrioles in cycling cells. Kif24 can bind and depolymerize microtubules in vitro, and its ectopic expression specifically remodels centriolar microtubules.\",\n      \"method\": \"Co-immunoprecipitation, siRNA depletion, in vitro microtubule depolymerization assay, immunofluorescence\",\n      \"journal\": \"Cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — Co-IP, in vitro microtubule assay, siRNA depletion with defined phenotypes, published in high-impact journal with multiple orthogonal methods\",\n      \"pmids\": [\"21620453\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"CEP104 interacts with CP110 and CEP97 at the centriole and is required for ciliogenesis, placing CEP104 in the CP110-CEP97 regulatory network at centrioles.\",\n      \"method\": \"Co-immunoprecipitation, siRNA depletion, immunofluorescence\",\n      \"journal\": \"Current biology : CB\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — Co-IP and functional depletion, single lab but two orthogonal methods\",\n      \"pmids\": [\"22885064\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"MARK4 knockdown arrests the ciliogenesis program before complete removal of the CP110-CEP97 inhibitory complex from the mother centriole, placing MARK4 and ODF2 upstream of CP110-CEP97 removal in the ciliogenesis pathway.\",\n      \"method\": \"siRNA depletion, immunofluorescence, epistasis analysis\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — epistasis/pathway placement by sequential knockdown, single lab\",\n      \"pmids\": [\"23400999\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"TTBK2 kinase has the potential to phosphorylate CEP97 in vitro, and TTBK2 recruitment to the mother centriole (via Cep164 binding) is required for CP110 and CEP97 removal during ciliogenesis initiation.\",\n      \"method\": \"In vitro kinase assay, TTBK2 variant expression/rescue, siRNA depletion, immunofluorescence\",\n      \"journal\": \"Genes to cells : devoted to molecular & cellular mechanisms\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — in vitro kinase assay showing CEP97 phosphorylation by TTBK2, plus siRNA/rescue epistasis; single lab\",\n      \"pmids\": [\"25297623\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"WDR8 and Cep135, proximal-end centriolar proteins, are required for unlocking the distal end of the mother centriole from the CP110-CEP97 inhibitory complex, placing them upstream of CP110-CEP97 removal in ciliogenesis.\",\n      \"method\": \"siRNA depletion, immunofluorescence, epistasis analysis\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — depletion with defined ciliogenesis phenotype and pathway placement relative to CP110-CEP97, single lab\",\n      \"pmids\": [\"26675238\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"In cytotoxic T lymphocytes (CTLs), CP110 and CEP97 remain associated with the mother centriole during centrosome docking at the immunological synapse, and no axoneme or transition zone ciliary structures form, establishing that centrosome docking can occur without ciliogenesis when CP110-CEP97 is retained.\",\n      \"method\": \"High-resolution TEM tomography, immunofluorescence, siRNA depletion\",\n      \"journal\": \"Current biology : CB\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — TEM tomography and immunofluorescence with functional consequence; single lab\",\n      \"pmids\": [\"26670998\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Crystal structure of CEP104's TOG domain was solved, and biophysical characterization demonstrated direct interactions between CEP104 and CP110, CEP97, EB protein, and tubulin, mapping the interaction network at the centriole distal tip.\",\n      \"method\": \"X-ray crystallography, biophysical binding assays (ITC/SPR), sequence analysis\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — crystal structure plus biophysical quantification of direct binding; single lab with multiple orthogonal methods\",\n      \"pmids\": [\"27402853\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"In Drosophila, Asterless (Asl, ortholog of Cep152) controls centriole length via the centriole protein Cep97; loss of Asl affects Cep97-dependent centriole length regulation in germline and somatic tissue.\",\n      \"method\": \"Genetic loss-of-function (Drosophila), immunofluorescence, phenotypic analysis of centriole length\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis in Drosophila model organism, single lab\",\n      \"pmids\": [\"27185836\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"MPP9 is recruited by KIF24 to the distal end of the mother centriole where it forms a ring-like structure and recruits the CP110-CEP97 complex by directly binding CEP97. Upon phosphorylation by TTBK2 at the onset of ciliogenesis, MPP9 is degraded via the ubiquitin-proteasome system, facilitating removal of CP110 and CEP97 from the mother centriole.\",\n      \"method\": \"Co-immunoprecipitation, super-resolution microscopy, siRNA depletion, ubiquitin-proteasome inhibitor treatment, mouse kidney analysis\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct binding shown by Co-IP, super-resolution localization, in vivo validation in mouse kidneys, multiple orthogonal methods\",\n      \"pmids\": [\"30375385\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"LRRC45 depletion does not impair removal of CP110-CEP97 from the mother centriole, establishing LRRC45 acts downstream of CP110-CEP97 removal in ciliogenesis.\",\n      \"method\": \"siRNA depletion, immunofluorescence, epistasis analysis\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — negative epistasis finding (LRRC45 not required for CP110-CEP97 removal), siRNA with immunofluorescence; single lab\",\n      \"pmids\": [\"30131441\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"In Drosophila, Cep97 is essential for formation of full-length centrioles in multiple tissues and interacts with the microtubule deacetylase Sirt2; both Sirt2 deletion and Atat1 (acetylase) deletion affect centriole size, supporting a model whereby Cep97 acts as a protective cap cooperating with the microtubule acetylation machinery to maintain centriole stability. Unlike in vertebrates, Drosophila Cep97 is only transiently removed from basal bodies and its loss strongly impairs ciliogenesis.\",\n      \"method\": \"Genetic loss-of-function (Drosophila), Co-immunoprecipitation/interaction screen, immunofluorescence, ultrastructural analysis\",\n      \"journal\": \"Current biology : CB\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic loss-of-function in multiple tissues, identification of Sirt2 as interactor, epistasis with acetylation machinery, multiple orthogonal methods\",\n      \"pmids\": [\"32589908\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"CEP97 interacts with Dyrk1a kinase in Xenopus multiciliated cells; Dyrk1a phosphorylates CEP97, which promotes recruitment of Plk1, a critical regulator of centriole disengagement that cooperates with Separase for centriole separation during multiciliogenesis. Knockdown of either CEP97 or Dyrk1a disrupts cilia formation and centriole disengagement, rescued by Separase overexpression.\",\n      \"method\": \"Co-immunoprecipitation, in vitro kinase assay, morpholino knockdown in Xenopus, rescue experiments with Separase overexpression, immunofluorescence\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — in vitro kinase assay, Co-IP, in vivo knockdown with genetic rescue; multiple orthogonal methods in Xenopus model\",\n      \"pmids\": [\"34787650\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"LUBAC-mediated linear ubiquitination of CP110 is required for CP110 removal from the mother centriole, with PRPF8 acting as a receptor for linear ubiquitin chains at the distal mother centriole. CEP97, as part of the CP110-CEP97 complex, is targeted by this LUBAC-dependent mechanism.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitination assays, siRNA depletion, immunofluorescence\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — biochemical ubiquitination assays and Co-IP, functional depletion; CEP97 implicated as part of complex but direct modification not shown for CEP97 itself\",\n      \"pmids\": [\"34813648\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"In Drosophila embryos, CP110 and CEP97 form a complex at the distal end of centrioles whose levels oscillate as centriole MTs grow; altering CP110 or Cep97 levels perturbs the Plk4 oscillation and cartwheel growth at the proximal end, revealing crosstalk between distal-end cap proteins and proximal-end centriole growth machinery.\",\n      \"method\": \"Live imaging, genetic manipulation (CP110/Cep97 overexpression/depletion), quantitative fluorescence microscopy in Drosophila embryos\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — live imaging and genetic perturbation showing cross-talk, single lab, Drosophila model\",\n      \"pmids\": [\"35707992\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"ENKD1 competes with CEP97 for binding to CP110; depletion of ENKD1 enhances the CP110-CEP97 interaction and detains CP110 at the mother centriole, blocking ciliogenesis. Simultaneous knockdown of ENKD1 and CP110 reverses the ciliogenesis defect, placing ENKD1 as a positive regulator of CP110 removal by competing with CEP97.\",\n      \"method\": \"Co-immunoprecipitation, competitive binding assay, siRNA depletion, double-knockdown epistasis, super-resolution microscopy, mouse knockout\",\n      \"journal\": \"EMBO reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — competitive binding shown by Co-IP, double-knockdown epistasis, in vivo mouse knockout, super-resolution microscopy; multiple orthogonal methods\",\n      \"pmids\": [\"35301795\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"The CP110-CEP97-CEP290 centrosomal complex is required for seeding the initial phosphorylated HSP27 ring during aggresome assembly at the centrosome; limiting amounts of CP110 in senescent cells impairs aggresome formation and aggregation of mutant huntingtin.\",\n      \"method\": \"High-resolution quantitative microscopy, siRNA depletion, immunofluorescence, functional aggregation assays\",\n      \"journal\": \"Nature cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — quantitative imaging and functional depletion establishing CP110-CEP97-CEP290 complex requirement for aggresome seeding; single lab\",\n      \"pmids\": [\"35411088\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"In C. elegans, homologs of Cep97 and Cep135/BLD10 are expressed in somatic tissues but not in early embryos, identified by proximity-labeling TurboID interactome mapping; their tissue-specific expression explains why these conserved centriolar components had not been previously identified in worm.\",\n      \"method\": \"TurboID proximity labeling, mass spectrometry, GFP-nanobody indirect proximity labeling in whole animal\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — proximity labeling MS identifies Cep97 homolog in somatic tissues; novel identification but no direct functional assay for Cep97 in worm\",\n      \"pmids\": [\"35442950\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"PCM1 and centriolar satellites facilitate efficient removal of CP110 and CEP97 from the distal mother centriole during ciliogenesis initiation; Pcm1-null RPE1 cells show reduced docking of the mother centriole to the ciliary vesicle and impaired CP110 and CEP97 removal.\",\n      \"method\": \"Genetic knockout (mouse and human RPE1 cells), immunofluorescence, ciliogenesis assays\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic KO in both mouse and human cell lines with defined CP110-CEP97 removal phenotype; single lab\",\n      \"pmids\": [\"36790165\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"In Drosophila, Cep97 is the central scaffolding unit required to recruit distal tip complex (DTC) components to the distal tip of centrioles; Cep104 and Cep97 cooperate during spermiogenesis to align spermatids and coordinate individualization.\",\n      \"method\": \"Proximity-labeling screen, genetic loss-of-function (Cep104 null flies), immunofluorescence, interactome mapping\",\n      \"journal\": \"Current biology : CB\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — proximity-labeling interactome plus genetic null fly analysis with multiple phenotypic readouts; establishes Cep97 as central scaffold for DTC\",\n      \"pmids\": [\"37729913\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"During cerebellar granule cell differentiation, CEP97 is recruited to docked mother centrioles in maturing neurons, capping them and preventing cilia regrowth, establishing a mechanism by which cilia are permanently lost in mature neurons.\",\n      \"method\": \"Single-cell transcriptomics, immunocytology, subcellular localization analysis across differentiation stages\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — localization tied to functional consequence (no cilia regrowth), single lab, correlative but with defined protein recruitment event\",\n      \"pmids\": [\"39705308\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"miR-106b in morphine-stimulated astrocyte-derived extracellular vesicles targets CEP97, reducing CEP97 levels in recipient astrocytes to promote primary ciliogenesis; anti-miR-106b delivery restores CEP97 expression and inhibits ciliogenesis.\",\n      \"method\": \"miRNA targeting validation, anti-miR delivery, immunofluorescence, in vivo mouse morphine tolerance model\",\n      \"journal\": \"Molecular therapy : the journal of the American Society of Gene Therapy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — miRNA-target relationship validated functionally with rescue, in vivo confirmation; single lab\",\n      \"pmids\": [\"37012704\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"CDK1 phosphorylates centriolar proteins including Centrobin at the centrosome, and CEP97-CCP110 restricts Centrobin localization to centrioles; CDK1-dependent phosphorylation suppresses Centrobin's centriole elongation activity. CEP97-CCP110 and CDK1 cooperatively restrict centriole elongation by inhibiting Centrobin via distinct mechanisms. Removal of CEP97 during mouse development causes centriole overelongation, impaired ciliogenesis, attenuated Hedgehog signaling, and disrupted heart development.\",\n      \"method\": \"Centrosome-specific phosphoproteomics, CDK1 inhibition, CEP97 knockout mice, ciliogenesis assays, HH signaling readouts, immunofluorescence\",\n      \"journal\": \"Genes & development\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — centrosome-specific phosphoproteomics, genetic KO in mice with developmental phenotypes, multiple orthogonal methods demonstrating CEP97-CCP110 restricts Centrobin\",\n      \"pmids\": [\"42140673\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"Expansion microscopy of Drosophila S2 cells reveals that Cep97 forms a ring structure at the distal tip of the centriole, clarifying its role as a cap on the growing centriole end.\",\n      \"method\": \"Expansion microscopy (ExM) of S2 cells and fly tissues\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct ultrastructural imaging with ExM revealing ring geometry; single lab, single method but high-resolution structural result\",\n      \"pmids\": [\"41347334\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CEP76 interacts with CCP110 and CEP97 (identified by proteomics), and CEP76 depletion impairs ciliogenesis; this places CEP76 in the CP110-CEP97 interaction network at the centrosome-cilium interface.\",\n      \"method\": \"Proximity proteomics, siRNA depletion, ciliary phenotype analysis in RPE1 cells\",\n      \"journal\": \"Science advances\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — proteomics identification of interaction, no direct functional dissection of CEP97-CEP76 relationship; single lab\",\n      \"pmids\": [\"41105778\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"EHD1, through its membrane tubulation function, directly promotes CP110/CEP97 removal from the mother centriole cap during ciliogenesis progression, linking membrane tubule formation at the mother centriole to distal cap disassembly.\",\n      \"method\": \"3D isotropic EM ultrastructure imaging, siRNA depletion of EHD1, quantitative analysis of CP110/CEP97 removal\",\n      \"journal\": \"bioRxiv (preprint)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct ultrastructural imaging plus functional depletion linking membrane tubulation to CP110/CEP97 removal; preprint, single lab\",\n      \"pmids\": [\"40894589\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"CEP97 is a conserved centriolar distal-tip protein that forms a cap complex with CP110 (and CEP290/CEP104) at the distal end of centrioles to suppress ciliogenesis in cycling cells and restrict centriole elongation by limiting Centrobin activity; its removal from the mother centriole — orchestrated by upstream regulators including MPP9, TTBK2, ENKD1, Dyrk1a (which phosphorylates CEP97 to recruit Plk1/Separase), and membrane-tubulating EHD1 — is required for ciliogenesis initiation, while in Drosophila Cep97 additionally maintains centriole structural integrity in cooperation with the microtubule acetylation machinery (Sirt2/Atat1) and acts as the central scaffold recruiting the distal tip complex.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CEP97 is a conserved centriolar distal-tip protein that, together with CP110, forms a cap complex at the distal end of centrioles which suppresses ciliogenesis in cycling cells; CEP97 directly recruits CP110 to centrosomes, and loss of either protein triggers ectopic primary cilia formation while enforced CP110 suppresses cilia assembly in quiescent cells [#0]. The CEP97-CP110 cap nucleates a broader distal-tip interaction network including the kinesin-13 motor KIF24, which is required to retain CP110 at the mother centriole, and CEP104, which bridges CP110, CEP97, EB protein and tubulin at the centriole tip [#1, #2, #7]. Productive ciliogenesis requires the regulated removal of this cap from the mother centriole, a step controlled by an extensive upstream network: MPP9 forms a ring that recruits the complex by directly binding CEP97 and is degraded upon TTBK2 phosphorylation, ENKD1 competes with CEP97 for CP110 binding to drive CP110 release, and PCM1/centriolar satellites and LUBAC-mediated linear ubiquitination further facilitate cap disassembly [#9, #4, #15, #18, #13]. CEP97 is itself a phosphorylation substrate: TTBK2 and Dyrk1a phosphorylate CEP97, with Dyrk1a-dependent phosphorylation promoting Plk1 recruitment to drive centriole disengagement during multiciliogenesis [#4, #12]. Beyond ciliary control, the CEP97-CP110 cap restricts centriole elongation by limiting Centrobin activity in cooperation with CDK1, and CEP97 loss in mice causes centriole overelongation, impaired ciliogenesis, attenuated Hedgehog signaling and disrupted heart development [#22]. In Drosophila, Cep97 forms a distal-tip ring and acts as the central scaffold recruiting the distal tip complex, maintaining centriole structural integrity in cooperation with the microtubule acetylation machinery (Sirt2/Atat1) [#11, #19, #23]. CEP97 levels also gate cell-type-specific cilia outcomes, capping docked mother centrioles to permanently prevent cilia regrowth in maturing neurons [#20].\",\n  \"teleology\": [\n    {\n      \"year\": 2007,\n      \"claim\": \"Established CEP97 as the physical recruiter of CP110 to centrosomes and defined the CEP97-CP110 complex as a collaborative inhibitor of ciliogenesis, answering what molecular activity restrains cilia assembly in cycling cells.\",\n      \"evidence\": \"Co-IP/MS complex purification, siRNA depletion with spindle/ploidy and ciliogenesis readouts, dominant-negative expression\",\n      \"pmids\": [\"17719545\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not define how the complex is removed to permit ciliogenesis\", \"No structural basis for CEP97-CP110 binding\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Showed that the kinesin-13 KIF24 partners with CEP97-CP110 and is required to maintain CP110 at mother centrioles, linking the cap to centriolar microtubule remodeling.\",\n      \"evidence\": \"Co-IP, siRNA depletion, in vitro microtubule depolymerization assay\",\n      \"pmids\": [\"21620453\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not define how KIF24 microtubule activity is regulated\", \"Role of CEP97 in KIF24 recruitment versus retention not separated\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Added CEP104 to the CEP97-CP110 distal-tip network and tied it functionally to ciliogenesis.\",\n      \"evidence\": \"Co-IP, siRNA depletion, immunofluorescence\",\n      \"pmids\": [\"22885064\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct versus indirect CEP97-CEP104 binding not resolved at this stage\", \"Single lab\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Identified TTBK2 as a kinase that phosphorylates CEP97 and is required for CP110/CEP97 removal, providing a kinase trigger for cap disassembly at ciliogenesis onset.\",\n      \"evidence\": \"In vitro kinase assay, TTBK2 rescue/variant expression, siRNA depletion\",\n      \"pmids\": [\"25297623\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Phosphosites on CEP97 and their functional consequence not mapped\", \"In vitro phosphorylation not confirmed at endogenous sites in vivo\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Placed proximal-end factors WDR8/Cep135 upstream of CP110-CEP97 removal, showing that distal cap disassembly is gated by proximal centriolar signals.\",\n      \"evidence\": \"siRNA depletion, epistasis analysis, immunofluorescence\",\n      \"pmids\": [\"26675238\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular link between proximal proteins and distal cap removal undefined\", \"Single lab\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Demonstrated that retention of CEP97-CP110 permits centrosome docking at the immunological synapse without ciliogenesis, dissociating docking from cilia formation.\",\n      \"evidence\": \"TEM tomography, immunofluorescence, siRNA depletion in CTLs\",\n      \"pmids\": [\"26670998\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism keeping the cap retained in CTLs not defined\", \"Single lab\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Provided structural and biophysical mapping of the distal-tip network, demonstrating CEP104 binds CEP97, CP110, EB protein and tubulin directly.\",\n      \"evidence\": \"X-ray crystallography of CEP104 TOG domain, ITC/SPR binding assays\",\n      \"pmids\": [\"27402853\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No structure of CEP97 itself\", \"CEP97 binding interface not crystallized\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Showed in Drosophila that Asterless/Cep152 controls centriole length via Cep97, implicating CEP97 in centriole elongation control.\",\n      \"evidence\": \"Drosophila genetic loss-of-function, immunofluorescence, centriole length phenotyping\",\n      \"pmids\": [\"27185836\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism by which Cep97 limits length not defined here\", \"Conservation to vertebrate length control untested\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Defined MPP9 as a direct CEP97 binder forming a recruiting ring, whose TTBK2-triggered proteasomal degradation enables cap removal, linking the kinase trigger to a degradation step.\",\n      \"evidence\": \"Co-IP, super-resolution microscopy, proteasome inhibition, mouse kidney analysis\",\n      \"pmids\": [\"30375385\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"E3 ligase for MPP9 not identified\", \"Whether CEP97 is itself degraded versus released unresolved\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Ordered LRRC45 downstream of CP110-CEP97 removal by showing its depletion does not block cap removal, refining pathway architecture.\",\n      \"evidence\": \"siRNA depletion, immunofluorescence, epistasis\",\n      \"pmids\": [\"30131441\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Negative result does not place LRRC45's exact step\", \"Single lab\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Established a structural-integrity role for Drosophila Cep97 as a protective cap cooperating with the microtubule acetylation machinery, distinguishing the fly cap (only transiently removed) from vertebrates.\",\n      \"evidence\": \"Drosophila genetic loss-of-function in multiple tissues, interaction screen identifying Sirt2, ultrastructural analysis\",\n      \"pmids\": [\"32589908\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether vertebrate CEP97 has an analogous acetylation-linked role untested\", \"Direct CEP97-Sirt2 binding interface not mapped\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Showed that Dyrk1a phosphorylates CEP97 to recruit Plk1 and drive centriole disengagement during multiciliogenesis, connecting CEP97 phosphorylation to centriole separation machinery.\",\n      \"evidence\": \"Co-IP, in vitro kinase assay, morpholino knockdown and Separase rescue in Xenopus\",\n      \"pmids\": [\"34787650\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"CEP97 phosphosites recognized by Plk1 docking not mapped\", \"Relationship between Dyrk1a and TTBK2 phosphorylation of CEP97 unresolved\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Implicated LUBAC-mediated linear ubiquitination and the PRPF8 ubiquitin receptor in removal of the CP110-CEP97 cap, adding a ubiquitin-based disassembly route.\",\n      \"evidence\": \"Co-IP, ubiquitination assays, siRNA depletion, immunofluorescence\",\n      \"pmids\": [\"34813648\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct ubiquitination of CEP97 itself not demonstrated\", \"How linear ubiquitin drives physical removal unresolved\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Revealed crosstalk in Drosophila embryos between the distal CP110-Cep97 cap and proximal Plk4-driven cartwheel growth, showing cap levels feed back on centriole biogenesis.\",\n      \"evidence\": \"Live imaging, genetic perturbation, quantitative fluorescence in Drosophila embryos\",\n      \"pmids\": [\"35707992\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular mediator of distal-to-proximal crosstalk unknown\", \"Single lab\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Identified ENKD1 as a competitor with CEP97 for CP110 binding that promotes CP110 release, defining a competition mechanism for cap disassembly.\",\n      \"evidence\": \"Co-IP, competitive binding assay, double-knockdown epistasis, super-resolution microscopy, mouse knockout\",\n      \"pmids\": [\"35301795\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How ENKD1 access to CP110 is timed during ciliogenesis unclear\", \"Effect on CEP97 retention versus CP110 retention not fully separated\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Extended CEP97-CP110 function beyond cilia by showing the CP110-CEP97-CEP290 complex seeds aggresome assembly via a phospho-HSP27 ring at the centrosome.\",\n      \"evidence\": \"Quantitative microscopy, siRNA depletion, aggregation assays\",\n      \"pmids\": [\"35411088\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct role of CEP97 versus CP110/CEP290 in seeding not dissected\", \"Single lab\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Mapped a Cep97 homolog to somatic tissues in C. elegans by interactome profiling, explaining its prior absence from worm studies.\",\n      \"evidence\": \"TurboID proximity labeling, mass spectrometry in whole animal\",\n      \"pmids\": [\"35442950\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No direct functional assay for worm Cep97\", \"Tissue-specific function untested\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Showed PCM1/centriolar satellites facilitate efficient CP110-CEP97 removal and mother-centriole docking to the ciliary vesicle.\",\n      \"evidence\": \"Mouse and human RPE1 knockouts, ciliogenesis assays, immunofluorescence\",\n      \"pmids\": [\"36790165\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether satellites act on the cap directly or via cargo delivery unresolved\", \"Single lab\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Established Drosophila Cep97 as the central scaffolding subunit recruiting the distal tip complex, and defined a Cep97-Cep104 role in spermiogenesis.\",\n      \"evidence\": \"Proximity-labeling interactome, Cep104-null fly genetics, immunofluorescence\",\n      \"pmids\": [\"37729913\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether vertebrate CEP97 is the equivalent DTC scaffold untested\", \"DTC assembly order not fully defined\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Demonstrated a regulatory input where miR-106b in morphine-stimulated EVs targets CEP97 to lower its levels and de-repress ciliogenesis in astrocytes.\",\n      \"evidence\": \"miRNA target validation, anti-miR rescue, in vivo mouse morphine model, immunofluorescence\",\n      \"pmids\": [\"37012704\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Other CEP97 mRNA regulators not surveyed\", \"Single lab\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Showed CEP97 is recruited to docked mother centrioles in maturing cerebellar neurons to cap them and permanently prevent cilia regrowth, defining a developmental cilia-loss mechanism.\",\n      \"evidence\": \"Single-cell transcriptomics, immunocytology, localization across differentiation\",\n      \"pmids\": [\"39705308\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Trigger for CEP97 recruitment in maturing neurons unknown\", \"Correlative localization, no perturbation of CEP97 in neurons\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Established that CEP97-CP110 restricts centriole elongation by limiting Centrobin in cooperation with CDK1, and that CEP97 loss in mice causes overelongation, ciliogenesis defects, attenuated Hedgehog signaling and heart defects, linking CEP97 to development.\",\n      \"evidence\": \"Centrosome-specific phosphoproteomics, CDK1 inhibition, CEP97 knockout mice, HH and ciliogenesis readouts\",\n      \"pmids\": [\"42140673\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct CEP97-Centrobin interaction not detailed\", \"Mechanism distinguishing CEP97-CP110 from CDK1 inhibition of Centrobin not fully resolved\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Resolved Cep97 as a ring structure at the distal tip in Drosophila by expansion microscopy, clarifying its geometry as a cap on the growing centriole end.\",\n      \"evidence\": \"Expansion microscopy of S2 cells and fly tissues\",\n      \"pmids\": [\"41347334\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Ring geometry not confirmed for vertebrate CEP97\", \"Molecular organization within the ring not resolved\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How CEP97 itself is physically displaced and turned over during cap removal — versus its partner CP110 — and the molecular interface CEP97 uses to bind CP110 remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No high-resolution structure of CEP97 or its CP110-binding interface\", \"Whether CEP97 is degraded, released, or sequestered during cap removal not established\", \"Functional phosphosites on CEP97 not mapped\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 9, 19]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 15, 22]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [0, 1, 9, 23]},\n      {\"term_id\": \"GO:0005814\", \"supporting_discovery_ids\": [0, 1, 9]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [1, 7]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [0, 9, 22]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [22, 20]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [22]}\n    ],\n    \"complexes\": [\n      \"CP110-CEP97 distal-tip cap complex\",\n      \"CP110-CEP97-CEP290 complex\",\n      \"centriole distal tip complex (DTC)\"\n    ],\n    \"partners\": [\n      \"CP110\",\n      \"KIF24\",\n      \"CEP104\",\n      \"MPP9\",\n      \"ENKD1\",\n      \"TTBK2\",\n      \"DYRK1A\",\n      \"SIRT2\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}