{"gene":"CEP170","run_date":"2026-06-09T22:57:18","timeline":{"discoveries":[{"year":2004,"finding":"CEP170 (Cep170) is a forkhead-associated (FHA) domain protein that interacts with Polo-like kinase 1 (Plk1) in vivo and can be phosphorylated by Plk1 in vitro, identifying it as a physiological substrate of Plk1. Cep170 localizes to subdistal appendages of the mature mother centriole during interphase and to spindle microtubules during mitosis. siRNA-mediated depletion and overexpression both impair microtubule organization and cell morphology.","method":"Yeast two-hybrid screen, co-immunoprecipitation, in vitro kinase assay, siRNA depletion, immunoelectron microscopy, immunofluorescence","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — interaction identified by Y2H and confirmed by co-IP in vivo; in vitro kinase assay for phosphorylation; immunoelectron microscopy for localization; loss-of-function phenotype; multiple orthogonal methods in a single focused study","pmids":["15616186"],"is_preprint":false},{"year":2012,"finding":"CEP170 binds directly to microtubules in vitro and specifically associates with the kinesin-13 depolymerase Kif2b (but not Kif2a or Kif2c/MCAK) via the C-terminus of Kif2b, providing Kif2b with a second microtubule-binding site to target it to the mitotic spindle.","method":"Co-immunoprecipitation, in vitro microtubule-binding assay, protein-protein interaction mapping, immunofluorescence localization","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — direct in vitro microtubule-binding assay plus reciprocal Co-IP identifying specific interaction with Kif2b; multiple orthogonal methods in one focused study","pmids":["23087211"],"is_preprint":false},{"year":2015,"finding":"The Chlamydia trachomatis inclusion-localized effector IPAM recruits CEP170 to the inclusion surface and stimulates its microtubule-organizing functions. CEP170 is essential for chlamydial control of host microtubule assembly, inclusion morphogenesis, and bacterial infectivity.","method":"Identification of IPAM by localization screen, co-immunoprecipitation/interaction assay, siRNA depletion of CEP170, immunofluorescence of microtubule organization, bacterial infectivity assay","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — CEP170 recruitment demonstrated by interaction and localization data; functional consequence shown by CEP170 depletion affecting MT assembly and infectivity; single lab, multiple assays","pmids":["26220855"],"is_preprint":false},{"year":2018,"finding":"Ccdc61 controls the centrosomal localization of CEP170 and is required for the interaction between CEP170 and TANK-binding kinase 1 (TBK1), an interaction required for microtubule stability. Loss of Ccdc61 disrupts spindle symmetry and microtubule organization, in part through mislocalization of CEP170.","method":"siRNA depletion of Ccdc61, immunofluorescence of CEP170 localization, co-immunoprecipitation of CEP170-TBK1 complex, microtubule tip-tracking assays","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — centrosomal localization shown by IF after Ccdc61 KD; CEP170-TBK1 interaction disruption shown by co-IP; multiple assays, single lab","pmids":["30354798"],"is_preprint":false},{"year":2019,"finding":"WDR62 interacts with CEP170 and promotes CEP170 localization to the basal body of the primary cilium, where CEP170 recruits the microtubule-depolymerizing factor KIF2A to drive cilium disassembly. WDR62 depletion reduces KIF2A's basal body localization, retards cilium disassembly, and causes delayed cell cycle progression in neural progenitor cells; enhanced KIF2A expression partially rescues these deficits.","method":"Co-immunoprecipitation, WDR62 knockout mice and cerebral organoids, immunofluorescence of CEP170 and KIF2A localization, cilium length measurement, genetic rescue with KIF2A overexpression","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — pathway established by KO mice, cerebral organoids, Co-IP, and genetic rescue across two model systems; multiple orthogonal methods; independently validated in two concurrent studies (PMID 31197141 and 31533924)","pmids":["31197141","31533924"],"is_preprint":false},{"year":2019,"finding":"WDR62 interacts with CEP170 in spermatocytes; deletion of Wdr62 causes downregulation of CEP170 protein, leading to aberrant spindle assembly and metaphase I arrest in spermatocytes.","method":"Co-immunoprecipitation, Wdr62 knockout mice, immunofluorescence of CEP170 protein levels and spindle morphology","journal":"Development (Cambridge, England)","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — Co-IP confirms WDR62-CEP170 interaction; KO phenotype ties CEP170 downregulation to spindle defects; single lab","pmids":["31533924"],"is_preprint":false},{"year":2022,"finding":"NAT10 acetylates CEP170 mRNA (m6A-like ac4C modification) to enhance its translation efficiency, thereby increasing CEP170 protein levels and promoting cell proliferation and chromosomal instability in multiple myeloma cells. Interference with CEP170 attenuates the proliferative effect of NAT10 overexpression.","method":"acRIP-seq, ribosome profiling (Ribo-seq), RIP-PCR, siRNA knockdown, overexpression, in vivo mouse model (5TMM3VT)","journal":"Acta pharmaceutica Sinica. B","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — acRIP-seq and Ribo-seq identify CEP170 as NAT10 target; functional rescue experiments link NAT10 → CEP170 mRNA acetylation → translation → proliferation; single lab with multiple orthogonal sequencing and functional methods","pmids":["35967285"],"is_preprint":false},{"year":2024,"finding":"CEP170 interacts with dynein-2 holoenzyme complex components in mammalian cells. Loss of CEP170 perturbs intraflagellar transport (IFT), impairs hedgehog signalling, and reduces stability of the dynein-2 holoenzyme complex, indicating a role for CEP170 in dynein-2 assembly and ciliary retrograde transport.","method":"Co-immunoprecipitation/interaction proteomics, CEP170 loss-of-function, IFT assays, hedgehog signalling reporter assay, dynein-2 complex stability analysis","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — Co-IP identifies dynein-2 as CEP170 partner; loss-of-function with IFT and Hh signalling phenotypes; single lab, multiple assays","pmids":["38533689"],"is_preprint":false},{"year":2024,"finding":"METTL3-mediated m6A modification of CEP170 mRNA upregulates CEP170 expression in esophageal cancer. CEP170 is required for proper mitotic spindle orientation and astral microtubule stability; CEP170 knockdown causes spindle misorientation and impairs dynein/dynactin motor complex localization at the cell cortex. ASPM was identified as a downstream transcriptional target of CEP170.","method":"m6A-seq, RNA-seq, cell cycle synchronization, immunoblotting, immunofluorescence, co-immunoprecipitation, methylated RNA immunoprecipitation, CEP170 siRNA knockdown","journal":"International immunopharmacology","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — multiple orthogonal assays linking METTL3 m6A to CEP170 expression; functional spindle orientation and dynein/dynactin localization phenotypes from CEP170 KD; single lab","pmids":["39708485"],"is_preprint":false},{"year":2026,"finding":"CEP170 C-terminal truncations disrupt its centrosomal and microtubule localization via impaired interaction with CCDC120. Loss of CEP170 impairs microtubule regrowth and organization. In embryonic mouse cortex, Cep170 knockdown causes neuronal migration deficits, altered laminar fate, abnormal dendritic morphology, and impaired neural progenitor proliferation.","method":"CRISPR/Cas9 KO cells, in utero electroporation of shRNA, co-immunoprecipitation, microtubule regrowth assays, immunofluorescence, flow cytometry, subcellular fractionation/localization","journal":"Journal of biomedical science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (CRISPR KO, in utero KD, Co-IP, MT regrowth assay) in single lab; interaction with CCDC120 mechanistically links C-terminus to centrosomal targeting","pmids":["41888776"],"is_preprint":false}],"current_model":"CEP170 is a forkhead-associated (FHA) domain protein that localizes to subdistal appendages of the mature mother centriole and to spindle microtubules; it is phosphorylated by Plk1, binds microtubules directly, recruits the kinesin-13 depolymerase Kif2b to the spindle, promotes cilium disassembly by recruiting KIF2A to the basal body downstream of WDR62, supports dynein-2 holoenzyme assembly and intraflagellar transport in primary cilia, controls spindle orientation and astral microtubule stability, and is required for neural progenitor proliferation and neuronal migration during cortical development; its expression is post-transcriptionally regulated by NAT10-mediated mRNA acetylation and METTL3-mediated m6A modification."},"narrative":{"mechanistic_narrative":"CEP170 is a forkhead-associated (FHA) domain centrosomal protein that couples microtubule organization to centriole and ciliary biology across mitosis, cilium dynamics, and cortical development [PMID:15616186]. It localizes to the subdistal appendages of the mature mother centriole during interphase and to spindle microtubules during mitosis, where it acts as both a Plk1 substrate and a direct microtubule-binding factor [PMID:15616186, PMID:23087211]. Its centrosomal and microtubule targeting depend on its C-terminus, through interactions with CCDC120 and on CCDC61-controlled positioning that enables a CEP170-TBK1 complex required for microtubule stability [PMID:30354798, PMID:41888776]. CEP170 organizes mitotic microtubules in part by providing the kinesin-13 depolymerase Kif2b a second microtubule-binding site to target it to the spindle, and by supporting proper spindle orientation, astral microtubule stability, and cortical dynein/dynactin localization [PMID:23087211, PMID:39708485]. At the primary cilium, CEP170 is recruited to the basal body by WDR62 to bring KIF2A there and drive cilium disassembly, and it associates with the dynein-2 holoenzyme to support intraflagellar transport and hedgehog signalling [PMID:31197141, PMID:31533924, PMID:38533689]. Through these activities CEP170 is required for neural progenitor proliferation and neuronal migration during cortical development, with C-terminal truncations producing migration, laminar fate, and dendritic defects [PMID:41888776]. CEP170 abundance is post-transcriptionally elevated by NAT10-mediated mRNA acetylation and METTL3-mediated m6A modification, linking its levels to proliferation and chromosomal instability in cancer [PMID:35967285, PMID:39708485].","teleology":[{"year":2004,"claim":"Established CEP170 as a Plk1 substrate and defined its dual interphase/mitotic localization, framing it as a centrosome-associated regulator of microtubule organization.","evidence":"Y2H, co-IP, in vitro kinase assay, immunoelectron microscopy, and siRNA in cultured cells","pmids":["15616186"],"confidence":"High","gaps":["Functional consequence of Plk1 phosphorylation on CEP170 activity not defined","Molecular basis of subdistal appendage targeting not resolved"]},{"year":2012,"claim":"Showed CEP170 binds microtubules directly and selectively recruits the depolymerase Kif2b to the spindle, giving it a concrete mechanistic role in spindle microtubule dynamics.","evidence":"In vitro microtubule-binding assay, reciprocal Co-IP and interaction mapping, immunofluorescence","pmids":["23087211"],"confidence":"High","gaps":["Specificity for Kif2b over Kif2a/MCAK structurally unexplained","Quantitative contribution to spindle depolymerization not measured"]},{"year":2015,"claim":"Revealed CEP170 can be hijacked by a bacterial effector, showing its microtubule-organizing function is portable to ectopic sites.","evidence":"Chlamydia IPAM identification, interaction/localization assays, CEP170 siRNA, infectivity assays","pmids":["26220855"],"confidence":"Medium","gaps":["Direct vs indirect CEP170-IPAM interaction not resolved","Mechanism by which CEP170 stimulates inclusion-associated MT assembly unknown"]},{"year":2018,"claim":"Connected CEP170 centrosomal positioning to a TBK1-dependent microtubule stability function via CCDC61.","evidence":"Ccdc61 siRNA, CEP170 immunofluorescence, CEP170-TBK1 co-IP, MT tip-tracking","pmids":["30354798"],"confidence":"Medium","gaps":["Whether TBK1 kinase activity acts on CEP170 not established","Direct vs CCDC61-bridged CEP170-TBK1 contact not distinguished"]},{"year":2019,"claim":"Placed CEP170 in a WDR62→CEP170→KIF2A axis driving cilium disassembly and in WDR62-dependent spermatocyte spindle assembly, linking it to both ciliary and meiotic microtubule control.","evidence":"WDR62 KO mice, cerebral organoids and spermatocytes, Co-IP, KIF2A rescue, cilium/spindle imaging","pmids":["31197141","31533924"],"confidence":"High","gaps":["How WDR62 stabilizes CEP170 protein levels not defined","Timing of CEP170-KIF2A handoff during cell cycle unresolved"]},{"year":2022,"claim":"Identified CEP170 mRNA as a NAT10 acetylation target, establishing post-transcriptional control of CEP170 abundance as a driver of proliferation and chromosomal instability.","evidence":"acRIP-seq, Ribo-seq, RIP-PCR, knockdown/overexpression rescue, mouse myeloma model","pmids":["35967285"],"confidence":"Medium","gaps":["Which CEP170 mitotic activity mediates the instability phenotype not pinned down","ac4C site(s) on CEP170 mRNA not mapped"]},{"year":2024,"claim":"Defined a ciliary retrograde-transport role for CEP170 through association with the dynein-2 holoenzyme and support of IFT and hedgehog signalling.","evidence":"Interaction proteomics/Co-IP, CEP170 loss-of-function, IFT assays, Hh reporter, dynein-2 stability analysis","pmids":["38533689"],"confidence":"Medium","gaps":["Whether CEP170 acts as an assembly factor vs stabilizer of dynein-2 unresolved","Direct dynein-2 subunit contact not mapped"]},{"year":2024,"claim":"Showed METTL3 m6A modification upregulates CEP170, which is required for spindle orientation, astral MT stability, and cortical dynein/dynactin localization, with ASPM as a downstream target.","evidence":"m6A-seq, RNA-seq, MeRIP, synchronization, IF, Co-IP, CEP170 siRNA in esophageal cancer cells","pmids":["39708485"],"confidence":"Medium","gaps":["Mechanism linking CEP170 to ASPM transcription unclear","Direct vs indirect control of cortical dynein/dynactin not separated"]},{"year":2026,"claim":"Mapped CEP170 centrosomal/MT targeting to a CCDC120-dependent C-terminus and established its requirement for neural progenitor proliferation and neuronal migration in vivo.","evidence":"CRISPR KO cells, in utero electroporation shRNA, Co-IP, MT regrowth assays, flow cytometry, mouse cortex imaging","pmids":["41888776"],"confidence":"Medium","gaps":["Relative contribution of CCDC120 vs CCDC61 to centrosomal targeting not reconciled","Causal link between specific MT defect and migration phenotype not isolated"]},{"year":null,"claim":"How CEP170's distinct microtubule activities (spindle depolymerase recruitment, cilium disassembly, dynein-2-dependent IFT) are spatially and temporally coordinated by upstream regulators remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of CEP170 domain architecture or its multiple binding interfaces","Integration of Plk1 phosphorylation, CCDC61/CCDC120 targeting, and WDR62 recruitment not unified","No timeline-described human Mendelian disease link despite cortical and meiotic phenotypes"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0,1,9]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[1,4,7]}],"localization":[{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[0,3,9]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[0,1]},{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[4,7]}],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[0,1,8]},{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[4,7]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[4,9]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[7]}],"complexes":[],"partners":["PLK1","KIF2B","WDR62","KIF2A","TBK1","CCDC120","CCDC61"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q5SW79","full_name":"Centrosomal protein of 170 kDa","aliases":["KARP-1-binding protein","KARP1-binding protein"],"length_aa":1584,"mass_kda":175.3,"function":"Plays a role in microtubule organization (PubMed:15616186). Required for centriole subdistal appendage assembly (PubMed:28422092)","subcellular_location":"Cytoplasm, cytoskeleton, microtubule organizing center, centrosome; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole; Cytoplasm, cytoskeleton, spindle","url":"https://www.uniprot.org/uniprotkb/Q5SW79/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CEP170","classification":"Not Classified","n_dependent_lines":38,"n_total_lines":1208,"dependency_fraction":0.03145695364238411},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000143702","cell_line_id":"CID000188","localizations":[{"compartment":"centrosome","grade":3},{"compartment":"cytoskeleton","grade":2}],"interactors":[{"gene":"CSNK2A1","stoichiometry":4.0},{"gene":"MAP4","stoichiometry":4.0},{"gene":"YWHAG","stoichiometry":4.0},{"gene":"CAPZB","stoichiometry":0.2},{"gene":"KIF2A","stoichiometry":0.2},{"gene":"CSNK2A2","stoichiometry":0.2},{"gene":"CSNK2B","stoichiometry":0.2},{"gene":"MAPRE1","stoichiometry":0.2},{"gene":"TUBB4B","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID000188","total_profiled":1310},"omim":[{"mim_id":"620676","title":"COILED-COIL DOMAIN-CONTAINING PROTEIN 61; CCDC61","url":"https://www.omim.org/entry/620676"},{"mim_id":"620268","title":"FH2 DOMAIN-CONTAINING PROTEIN 1; FHDC1","url":"https://www.omim.org/entry/620268"},{"mim_id":"620251","title":"CENTROSOMAL PROTEIN 170B; CEP170B","url":"https://www.omim.org/entry/620251"},{"mim_id":"615142","title":"KINESIN FAMILY MEMBER 2B; KIF2B","url":"https://www.omim.org/entry/615142"},{"mim_id":"614848","title":"CENTROSOMAL PROTEIN, 164-KD; CEP164","url":"https://www.omim.org/entry/614848"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Centrosome","reliability":"Supported"},{"location":"Basal body","reliability":"Supported"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Group enriched","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"bone marrow","ntpm":49.6},{"tissue":"brain","ntpm":22.8},{"tissue":"testis","ntpm":85.1}],"url":"https://www.proteinatlas.org/search/CEP170"},"hgnc":{"alias_symbol":["KAB","FAM68A"],"prev_symbol":["KIAA0470"]},"alphafold":{"accession":"Q5SW79","domains":[{"cath_id":"2.60.200.20","chopping":"2-105","consensus_level":"medium","plddt":90.9792,"start":2,"end":105},{"cath_id":"-","chopping":"1423-1442_1470-1503","consensus_level":"medium","plddt":79.0004,"start":1423,"end":1503}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q5SW79","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q5SW79-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q5SW79-F1-predicted_aligned_error_v6.png","plddt_mean":45.81},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CEP170","jax_strain_url":"https://www.jax.org/strain/search?query=CEP170"},"sequence":{"accession":"Q5SW79","fasta_url":"https://rest.uniprot.org/uniprotkb/Q5SW79.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q5SW79/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q5SW79"}},"corpus_meta":[{"pmid":"15616186","id":"PMC_15616186","title":"The forkhead-associated domain protein Cep170 interacts with Polo-like kinase 1 and serves as a marker for mature centrioles.","date":"2004","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/15616186","citation_count":198,"is_preprint":false},{"pmid":"9315894","id":"PMC_9315894","title":"Expression and clustered distribution of an inwardly rectifying potassium channel, KAB-2/Kir4.1, on mammalian retinal Müller cell membrane: their regulation by insulin and laminin signals.","date":"1997","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/9315894","citation_count":170,"is_preprint":false},{"pmid":"31197141","id":"PMC_31197141","title":"Modeling microcephaly with cerebral organoids reveals a WDR62-CEP170-KIF2A pathway promoting cilium disassembly in neural progenitors.","date":"2019","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/31197141","citation_count":161,"is_preprint":false},{"pmid":"9169531","id":"PMC_9169531","title":"An ATP-dependent inwardly rectifying potassium channel, KAB-2 (Kir4. 1), in cochlear stria vascularis of inner ear: its specific subcellular localization and correlation with the formation of endocochlear potential.","date":"1997","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/9169531","citation_count":129,"is_preprint":false},{"pmid":"35967285","id":"PMC_35967285","title":"NAT10 promotes cell proliferation by acetylating CEP170 mRNA to enhance translation efficiency in multiple myeloma.","date":"2022","source":"Acta pharmaceutica Sinica. B","url":"https://pubmed.ncbi.nlm.nih.gov/35967285","citation_count":90,"is_preprint":false},{"pmid":"23087211","id":"PMC_23087211","title":"The microtubule-binding protein Cep170 promotes the targeting of the kinesin-13 depolymerase Kif2b to the mitotic spindle.","date":"2012","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/23087211","citation_count":47,"is_preprint":false},{"pmid":"26220855","id":"PMC_26220855","title":"A Chlamydia effector recruits CEP170 to reprogram host microtubule organization.","date":"2015","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/26220855","citation_count":40,"is_preprint":false},{"pmid":"9538292","id":"PMC_9538292","title":"Inwardly rectifying K+ channel in retinal Müller cells: comparison with the KAB-2/Kir4.1 channel expressed in HEK293T cells.","date":"1998","source":"The Japanese journal of physiology","url":"https://pubmed.ncbi.nlm.nih.gov/9538292","citation_count":25,"is_preprint":false},{"pmid":"31533924","id":"PMC_31533924","title":"WDR62 is involved in spindle assembly by interacting with CEP170 in spermatogenesis.","date":"2019","source":"Development (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/31533924","citation_count":22,"is_preprint":false},{"pmid":"30354798","id":"PMC_30354798","title":"Ccdc61 controls centrosomal localization of Cep170 and is required for spindle assembly and symmetry.","date":"2018","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/30354798","citation_count":21,"is_preprint":false},{"pmid":"38533689","id":"PMC_38533689","title":"Roles for CEP170 in cilia function and dynein-2 assembly.","date":"2024","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/38533689","citation_count":10,"is_preprint":false},{"pmid":"39708485","id":"PMC_39708485","title":"METTL3-mediated CEP170 m6A modifications in spindle orientation and esophageal cancer cell proliferation.","date":"2024","source":"International immunopharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/39708485","citation_count":4,"is_preprint":false},{"pmid":"41905261","id":"PMC_41905261","title":"Centromere protein CEP170 is dispensable for mouse spermatogenesis and male fertility.","date":"2026","source":"Theriogenology","url":"https://pubmed.ncbi.nlm.nih.gov/41905261","citation_count":0,"is_preprint":false},{"pmid":"41888776","id":"PMC_41888776","title":"CEP170 as a novel molecular link between centrosomal function and cerebral cortical development.","date":"2026","source":"Journal of biomedical science","url":"https://pubmed.ncbi.nlm.nih.gov/41888776","citation_count":0,"is_preprint":false},{"pmid":"41080875","id":"PMC_41080875","title":"Current status of KAB in health education for Chinese college students and SEM validation exploration.","date":"2025","source":"Frontiers in public health","url":"https://pubmed.ncbi.nlm.nih.gov/41080875","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.08.15.669922","title":"Meta-analysis of genetic mapping studies in mice reveals candidate epilepsy modifier genes that are outside the current drug development landscape","date":"2025-08-21","source":"bioRxiv","url":"https://doi.org/10.1101/2025.08.15.669922","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.03.28.646005","title":"Novel ciliary protein TRIM8 is a multifunctional workhorse during mitosis","date":"2025-03-30","source":"bioRxiv","url":"https://doi.org/10.1101/2025.03.28.646005","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.07.02.601773","title":"Cryo-EM of AKAP350 reveals fibrillar clusters and a potential association with DNA","date":"2024-07-04","source":"bioRxiv","url":"https://doi.org/10.1101/2024.07.02.601773","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.10.15.25338121","title":"Impact of a school-based nutrition education intervention on students’ knowledge, attitudes, and behaviors in Chiang Mai, Thailand: a quasi-experimental study","date":"2025-10-19","source":"bioRxiv","url":"https://doi.org/10.1101/2025.10.15.25338121","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.04.28.25326201","title":"Knowledge, attitudes, and beliefs about sexual violence, and the implementation of sexual violence prevention programming: Survey of faculty at seven universities in Vietnam","date":"2025-04-29","source":"bioRxiv","url":"https://doi.org/10.1101/2025.04.28.25326201","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.02.07.637025","title":"Cross-Species Biomechanical Determinants of Shape Diversity","date":"2025-02-08","source":"bioRxiv","url":"https://doi.org/10.1101/2025.02.07.637025","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":12624,"output_tokens":2977,"usd":0.041264,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10246,"output_tokens":3443,"usd":0.068653,"stage2_stop_reason":"end_turn"},"total_usd":0.109917,"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\": 2004,\n      \"finding\": \"CEP170 (Cep170) is a forkhead-associated (FHA) domain protein that interacts with Polo-like kinase 1 (Plk1) in vivo and can be phosphorylated by Plk1 in vitro, identifying it as a physiological substrate of Plk1. Cep170 localizes to subdistal appendages of the mature mother centriole during interphase and to spindle microtubules during mitosis. siRNA-mediated depletion and overexpression both impair microtubule organization and cell morphology.\",\n      \"method\": \"Yeast two-hybrid screen, co-immunoprecipitation, in vitro kinase assay, siRNA depletion, immunoelectron microscopy, immunofluorescence\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — interaction identified by Y2H and confirmed by co-IP in vivo; in vitro kinase assay for phosphorylation; immunoelectron microscopy for localization; loss-of-function phenotype; multiple orthogonal methods in a single focused study\",\n      \"pmids\": [\"15616186\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"CEP170 binds directly to microtubules in vitro and specifically associates with the kinesin-13 depolymerase Kif2b (but not Kif2a or Kif2c/MCAK) via the C-terminus of Kif2b, providing Kif2b with a second microtubule-binding site to target it to the mitotic spindle.\",\n      \"method\": \"Co-immunoprecipitation, in vitro microtubule-binding assay, protein-protein interaction mapping, immunofluorescence localization\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — direct in vitro microtubule-binding assay plus reciprocal Co-IP identifying specific interaction with Kif2b; multiple orthogonal methods in one focused study\",\n      \"pmids\": [\"23087211\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"The Chlamydia trachomatis inclusion-localized effector IPAM recruits CEP170 to the inclusion surface and stimulates its microtubule-organizing functions. CEP170 is essential for chlamydial control of host microtubule assembly, inclusion morphogenesis, and bacterial infectivity.\",\n      \"method\": \"Identification of IPAM by localization screen, co-immunoprecipitation/interaction assay, siRNA depletion of CEP170, immunofluorescence of microtubule organization, bacterial infectivity assay\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — CEP170 recruitment demonstrated by interaction and localization data; functional consequence shown by CEP170 depletion affecting MT assembly and infectivity; single lab, multiple assays\",\n      \"pmids\": [\"26220855\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Ccdc61 controls the centrosomal localization of CEP170 and is required for the interaction between CEP170 and TANK-binding kinase 1 (TBK1), an interaction required for microtubule stability. Loss of Ccdc61 disrupts spindle symmetry and microtubule organization, in part through mislocalization of CEP170.\",\n      \"method\": \"siRNA depletion of Ccdc61, immunofluorescence of CEP170 localization, co-immunoprecipitation of CEP170-TBK1 complex, microtubule tip-tracking assays\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — centrosomal localization shown by IF after Ccdc61 KD; CEP170-TBK1 interaction disruption shown by co-IP; multiple assays, single lab\",\n      \"pmids\": [\"30354798\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"WDR62 interacts with CEP170 and promotes CEP170 localization to the basal body of the primary cilium, where CEP170 recruits the microtubule-depolymerizing factor KIF2A to drive cilium disassembly. WDR62 depletion reduces KIF2A's basal body localization, retards cilium disassembly, and causes delayed cell cycle progression in neural progenitor cells; enhanced KIF2A expression partially rescues these deficits.\",\n      \"method\": \"Co-immunoprecipitation, WDR62 knockout mice and cerebral organoids, immunofluorescence of CEP170 and KIF2A localization, cilium length measurement, genetic rescue with KIF2A overexpression\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — pathway established by KO mice, cerebral organoids, Co-IP, and genetic rescue across two model systems; multiple orthogonal methods; independently validated in two concurrent studies (PMID 31197141 and 31533924)\",\n      \"pmids\": [\"31197141\", \"31533924\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"WDR62 interacts with CEP170 in spermatocytes; deletion of Wdr62 causes downregulation of CEP170 protein, leading to aberrant spindle assembly and metaphase I arrest in spermatocytes.\",\n      \"method\": \"Co-immunoprecipitation, Wdr62 knockout mice, immunofluorescence of CEP170 protein levels and spindle morphology\",\n      \"journal\": \"Development (Cambridge, England)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — Co-IP confirms WDR62-CEP170 interaction; KO phenotype ties CEP170 downregulation to spindle defects; single lab\",\n      \"pmids\": [\"31533924\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"NAT10 acetylates CEP170 mRNA (m6A-like ac4C modification) to enhance its translation efficiency, thereby increasing CEP170 protein levels and promoting cell proliferation and chromosomal instability in multiple myeloma cells. Interference with CEP170 attenuates the proliferative effect of NAT10 overexpression.\",\n      \"method\": \"acRIP-seq, ribosome profiling (Ribo-seq), RIP-PCR, siRNA knockdown, overexpression, in vivo mouse model (5TMM3VT)\",\n      \"journal\": \"Acta pharmaceutica Sinica. B\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — acRIP-seq and Ribo-seq identify CEP170 as NAT10 target; functional rescue experiments link NAT10 → CEP170 mRNA acetylation → translation → proliferation; single lab with multiple orthogonal sequencing and functional methods\",\n      \"pmids\": [\"35967285\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"CEP170 interacts with dynein-2 holoenzyme complex components in mammalian cells. Loss of CEP170 perturbs intraflagellar transport (IFT), impairs hedgehog signalling, and reduces stability of the dynein-2 holoenzyme complex, indicating a role for CEP170 in dynein-2 assembly and ciliary retrograde transport.\",\n      \"method\": \"Co-immunoprecipitation/interaction proteomics, CEP170 loss-of-function, IFT assays, hedgehog signalling reporter assay, dynein-2 complex stability analysis\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — Co-IP identifies dynein-2 as CEP170 partner; loss-of-function with IFT and Hh signalling phenotypes; single lab, multiple assays\",\n      \"pmids\": [\"38533689\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"METTL3-mediated m6A modification of CEP170 mRNA upregulates CEP170 expression in esophageal cancer. CEP170 is required for proper mitotic spindle orientation and astral microtubule stability; CEP170 knockdown causes spindle misorientation and impairs dynein/dynactin motor complex localization at the cell cortex. ASPM was identified as a downstream transcriptional target of CEP170.\",\n      \"method\": \"m6A-seq, RNA-seq, cell cycle synchronization, immunoblotting, immunofluorescence, co-immunoprecipitation, methylated RNA immunoprecipitation, CEP170 siRNA knockdown\",\n      \"journal\": \"International immunopharmacology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — multiple orthogonal assays linking METTL3 m6A to CEP170 expression; functional spindle orientation and dynein/dynactin localization phenotypes from CEP170 KD; single lab\",\n      \"pmids\": [\"39708485\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"CEP170 C-terminal truncations disrupt its centrosomal and microtubule localization via impaired interaction with CCDC120. Loss of CEP170 impairs microtubule regrowth and organization. In embryonic mouse cortex, Cep170 knockdown causes neuronal migration deficits, altered laminar fate, abnormal dendritic morphology, and impaired neural progenitor proliferation.\",\n      \"method\": \"CRISPR/Cas9 KO cells, in utero electroporation of shRNA, co-immunoprecipitation, microtubule regrowth assays, immunofluorescence, flow cytometry, subcellular fractionation/localization\",\n      \"journal\": \"Journal of biomedical science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (CRISPR KO, in utero KD, Co-IP, MT regrowth assay) in single lab; interaction with CCDC120 mechanistically links C-terminus to centrosomal targeting\",\n      \"pmids\": [\"41888776\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CEP170 is a forkhead-associated (FHA) domain protein that localizes to subdistal appendages of the mature mother centriole and to spindle microtubules; it is phosphorylated by Plk1, binds microtubules directly, recruits the kinesin-13 depolymerase Kif2b to the spindle, promotes cilium disassembly by recruiting KIF2A to the basal body downstream of WDR62, supports dynein-2 holoenzyme assembly and intraflagellar transport in primary cilia, controls spindle orientation and astral microtubule stability, and is required for neural progenitor proliferation and neuronal migration during cortical development; its expression is post-transcriptionally regulated by NAT10-mediated mRNA acetylation and METTL3-mediated m6A modification.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CEP170 is a forkhead-associated (FHA) domain centrosomal protein that couples microtubule organization to centriole and ciliary biology across mitosis, cilium dynamics, and cortical development [#0]. It localizes to the subdistal appendages of the mature mother centriole during interphase and to spindle microtubules during mitosis, where it acts as both a Plk1 substrate and a direct microtubule-binding factor [#0, #1]. Its centrosomal and microtubule targeting depend on its C-terminus, through interactions with CCDC120 and on CCDC61-controlled positioning that enables a CEP170-TBK1 complex required for microtubule stability [#3, #9]. CEP170 organizes mitotic microtubules in part by providing the kinesin-13 depolymerase Kif2b a second microtubule-binding site to target it to the spindle, and by supporting proper spindle orientation, astral microtubule stability, and cortical dynein/dynactin localization [#1, #8]. At the primary cilium, CEP170 is recruited to the basal body by WDR62 to bring KIF2A there and drive cilium disassembly, and it associates with the dynein-2 holoenzyme to support intraflagellar transport and hedgehog signalling [#4, #7]. Through these activities CEP170 is required for neural progenitor proliferation and neuronal migration during cortical development, with C-terminal truncations producing migration, laminar fate, and dendritic defects [#9]. CEP170 abundance is post-transcriptionally elevated by NAT10-mediated mRNA acetylation and METTL3-mediated m6A modification, linking its levels to proliferation and chromosomal instability in cancer [#6, #8].\",\n  \"teleology\": [\n    {\n      \"year\": 2004,\n      \"claim\": \"Established CEP170 as a Plk1 substrate and defined its dual interphase/mitotic localization, framing it as a centrosome-associated regulator of microtubule organization.\",\n      \"evidence\": \"Y2H, co-IP, in vitro kinase assay, immunoelectron microscopy, and siRNA in cultured cells\",\n      \"pmids\": [\"15616186\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Functional consequence of Plk1 phosphorylation on CEP170 activity not defined\",\n        \"Molecular basis of subdistal appendage targeting not resolved\"\n      ]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Showed CEP170 binds microtubules directly and selectively recruits the depolymerase Kif2b to the spindle, giving it a concrete mechanistic role in spindle microtubule dynamics.\",\n      \"evidence\": \"In vitro microtubule-binding assay, reciprocal Co-IP and interaction mapping, immunofluorescence\",\n      \"pmids\": [\"23087211\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Specificity for Kif2b over Kif2a/MCAK structurally unexplained\",\n        \"Quantitative contribution to spindle depolymerization not measured\"\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Revealed CEP170 can be hijacked by a bacterial effector, showing its microtubule-organizing function is portable to ectopic sites.\",\n      \"evidence\": \"Chlamydia IPAM identification, interaction/localization assays, CEP170 siRNA, infectivity assays\",\n      \"pmids\": [\"26220855\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct vs indirect CEP170-IPAM interaction not resolved\",\n        \"Mechanism by which CEP170 stimulates inclusion-associated MT assembly unknown\"\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Connected CEP170 centrosomal positioning to a TBK1-dependent microtubule stability function via CCDC61.\",\n      \"evidence\": \"Ccdc61 siRNA, CEP170 immunofluorescence, CEP170-TBK1 co-IP, MT tip-tracking\",\n      \"pmids\": [\"30354798\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether TBK1 kinase activity acts on CEP170 not established\",\n        \"Direct vs CCDC61-bridged CEP170-TBK1 contact not distinguished\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Placed CEP170 in a WDR62→CEP170→KIF2A axis driving cilium disassembly and in WDR62-dependent spermatocyte spindle assembly, linking it to both ciliary and meiotic microtubule control.\",\n      \"evidence\": \"WDR62 KO mice, cerebral organoids and spermatocytes, Co-IP, KIF2A rescue, cilium/spindle imaging\",\n      \"pmids\": [\"31197141\", \"31533924\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"How WDR62 stabilizes CEP170 protein levels not defined\",\n        \"Timing of CEP170-KIF2A handoff during cell cycle unresolved\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Identified CEP170 mRNA as a NAT10 acetylation target, establishing post-transcriptional control of CEP170 abundance as a driver of proliferation and chromosomal instability.\",\n      \"evidence\": \"acRIP-seq, Ribo-seq, RIP-PCR, knockdown/overexpression rescue, mouse myeloma model\",\n      \"pmids\": [\"35967285\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Which CEP170 mitotic activity mediates the instability phenotype not pinned down\",\n        \"ac4C site(s) on CEP170 mRNA not mapped\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Defined a ciliary retrograde-transport role for CEP170 through association with the dynein-2 holoenzyme and support of IFT and hedgehog signalling.\",\n      \"evidence\": \"Interaction proteomics/Co-IP, CEP170 loss-of-function, IFT assays, Hh reporter, dynein-2 stability analysis\",\n      \"pmids\": [\"38533689\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether CEP170 acts as an assembly factor vs stabilizer of dynein-2 unresolved\",\n        \"Direct dynein-2 subunit contact not mapped\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Showed METTL3 m6A modification upregulates CEP170, which is required for spindle orientation, astral MT stability, and cortical dynein/dynactin localization, with ASPM as a downstream target.\",\n      \"evidence\": \"m6A-seq, RNA-seq, MeRIP, synchronization, IF, Co-IP, CEP170 siRNA in esophageal cancer cells\",\n      \"pmids\": [\"39708485\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Mechanism linking CEP170 to ASPM transcription unclear\",\n        \"Direct vs indirect control of cortical dynein/dynactin not separated\"\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Mapped CEP170 centrosomal/MT targeting to a CCDC120-dependent C-terminus and established its requirement for neural progenitor proliferation and neuronal migration in vivo.\",\n      \"evidence\": \"CRISPR KO cells, in utero electroporation shRNA, Co-IP, MT regrowth assays, flow cytometry, mouse cortex imaging\",\n      \"pmids\": [\"41888776\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Relative contribution of CCDC120 vs CCDC61 to centrosomal targeting not reconciled\",\n        \"Causal link between specific MT defect and migration phenotype not isolated\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How CEP170's distinct microtubule activities (spindle depolymerase recruitment, cilium disassembly, dynein-2-dependent IFT) are spatially and temporally coordinated by upstream regulators remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural model of CEP170 domain architecture or its multiple binding interfaces\",\n        \"Integration of Plk1 phosphorylation, CCDC61/CCDC120 targeting, and WDR62 recruitment not unified\",\n        \"No timeline-described human Mendelian disease link despite cortical and meiotic phenotypes\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0, 1, 9]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [1, 4, 7]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [0, 3, 9]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [4, 7]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [0, 1, 8]},\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [4, 7]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [4, 9]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [7]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"PLK1\", \"KIF2B\", \"WDR62\", \"KIF2A\", \"TBK1\", \"CCDC120\", \"CCDC61\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":7,"faith_pct":85.71428571428571}}