{"gene":"CEP152","run_date":"2026-06-09T22:57:18","timeline":{"discoveries":[{"year":2010,"finding":"CEP152 interacts with the cryptic Polo-box (CPB) of PLK4 via its N-terminal domain (first 217 residues), and this interaction is required for PLK4 recruitment to centrosomes and for PLK4-induced centriole overduplication.","method":"Co-immunoprecipitation, overexpression of truncated CEP152(1-217) to mislocalize PLK4, siRNA knockdown with centriole duplication readout","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — two independent labs (PMID:21059844 and PMID:21059850) using reciprocal Co-IP, domain-mapping, and loss-of-function with orthogonal readouts, replicated in the same year","pmids":["21059844","21059850"],"is_preprint":false},{"year":2010,"finding":"CEP152 is required for recruitment of CPAP to the centrosome; depletion of CEP152 causes loss of CPAP, monopolar mitotic spindles, and failure of centriole duplication.","method":"siRNA knockdown, immunofluorescence for CPAP and centriole markers, spindle formation assay","journal":"The Journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — single lab (PMID:21059844), clean knockdown with defined phenotypic readouts but not independently replicated for CPAP specifically","pmids":["21059844"],"is_preprint":false},{"year":2010,"finding":"CEP152 can be phosphorylated by PLK4 in vitro, indicating CEP152 is a PLK4 substrate.","method":"In vitro kinase assay with recombinant PLK4 and CEP152","journal":"The Journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — direct in vitro kinase assay in single lab (PMID:21059850); not yet confirmed with mutagenesis of phosphorylation sites","pmids":["21059850"],"is_preprint":false},{"year":2010,"finding":"CEP152 loss-of-function leads to accumulation of genomic defects through replicative stress, enhanced ATM signaling activation, and increased H2AX phosphorylation, identifying CEP152 as a genome maintenance/DNA damage response regulator.","method":"Homozygosity mapping and exome sequencing to identify CEP152 mutations in Seckel syndrome; functional assays measuring ATM signaling and H2AX phosphorylation in patient-derived cells","journal":"Nature genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — patient genetics plus cellular functional assays in single lab (PMID:21131973); two orthogonal readouts (ATM activation, H2AX phosphorylation)","pmids":["21131973"],"is_preprint":false},{"year":2010,"finding":"A CEP152 truncation mutation that removes one-third of the protein prevents its localization to centrosomes, demonstrating that the C-terminal region is required for centrosomal targeting.","method":"Transfection of truncated CEP152 construct in cells, immunofluorescence microscopy","journal":"American journal of human genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — direct localization experiment with defined construct in single study (PMID:20598275)","pmids":["20598275"],"is_preprint":false},{"year":2008,"finding":"CEP152 (vertebrate ortholog of Drosophila Asterless/Asl) is essential for daughter centriole formation; depletion eliminates multiple centriolar markers while only mildly affecting pericentriolar material (PCM) function, placing CEP152 early in centriole duplication. CEP152/Asl localizes closely associated with the centriole wall but is not part of the centriole structure itself.","method":"Loss-of-function allele characterization in Drosophila (mecD asl allele), morpholino knockdown in zebrafish, immunolocalization of centriole markers and PCM components","journal":"Genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multi-organism (Drosophila + zebrafish), multiple centriole markers analyzed, functional rescue with vertebrate Cep152 (PMID:18854586)","pmids":["18854586"],"is_preprint":false},{"year":2013,"finding":"CEP192 and CEP152 cooperate to recruit PLK4 to mammalian centrioles: CEP192 is required for centrosomal recruitment of CEP152 (placing CEP192 upstream), and double-depletion of both proteins completely abolishes PLK4 binding and centriole duplication. PLK4 binding regions of CEP192 and CEP152 (residues 190–240 and 1–46, respectively) are rich in negatively charged amino acids, suggesting electrostatic interactions with PLK4's positively charged polo-box domain.","method":"Sequential siRNA double-depletion, Co-IP, domain-deletion mapping, super-resolution microscopy","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 / Strong — replicated by two independent labs in the same year (PMID:23641073 and PMID:24277814) with reciprocal Co-IP, domain mapping, and epistasis experiments","pmids":["23641073","24277814"],"is_preprint":false},{"year":2013,"finding":"CEP192 and CEP152 serve as two distinct hierarchical scaffolds that recruit PLK4 to distinct subcentrosomal regions in a temporally regulated manner; CEP192 and CEP152 competitively interact with the cryptic polo-box of PLK4 through homologous N-terminal sequences containing acidic-α-helix and N/Q-rich motifs. Expression of either N-terminal fragment alone is sufficient to delocalize PLK4 from centrosomes.","method":"Biochemical competition assays, Co-IP with truncated constructs, live-cell imaging, loss-of-function by depletion with centriole duplication readout","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 / Strong — PMID:24277814, multiple orthogonal methods (Co-IP, domain mapping, competition assay, live imaging, depletion epistasis), corroborated by PMID:23641073","pmids":["24277814","23641073"],"is_preprint":false},{"year":2013,"finding":"CEP57, CEP63, and CEP152 form a ring-like complex localizing around the proximal end of centrioles, as revealed by selective chemical crosslinking and super-resolution microscopy. CEP152 and PLK4 reside in two separable structures at the centrosome, suggesting PLK4 contacts CEP152 only transiently.","method":"Selective chemical crosslinking (SNAP-tag-based), super-resolution (STED) microscopy, pulldown assays","journal":"Current biology : CB","confidence":"High","confidence_rationale":"Tier 1 / Moderate — chemical crosslinking combined with super-resolution imaging and biochemical assays in single lab (PMID:23333316); orthogonal structural and biochemical methods","pmids":["23333316"],"is_preprint":false},{"year":2018,"finding":"In mouse oocytes (acentriolar MTOCs), CEP152 localizes to MTOCs at the germinal vesicle stage and is excluded from MTOCs after germinal vesicle breakdown; this exclusion is regulated by CDK1 activity and is involved in MTOC fragmentation during meiotic spindle formation.","method":"Live-cell imaging, immunofluorescence of staged oocytes, siRNA depletion with CDK1 inhibitor treatment and MTOC/spindle morphology readouts","journal":"FASEB journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization with CDK1 inhibitor functional test in mouse oocytes (PMID:28970258); two orthogonal approaches but single lab","pmids":["28970258"],"is_preprint":false},{"year":2020,"finding":"CEP63 and CEP152 cooperatively form a heterotetrameric complex that undergoes liquid-liquid phase separation (LLPS) to generate higher-order self-assemblies at centrosomes. Two hydrophobic motifs, one each from CEP63 and CEP152, are required for phase-separating condensates and high-molecular-weight assembly. LLPS disruptor 1,6-hexanediol diminishes endogenous CEP63 and CEP152 centrosome localization.","method":"In vitro reconstitution of purified CEP63•CEP152 complex, FRAP, hexanediol treatment, mutagenesis of hydrophobic motifs, correlative light-electron microscopy (CLEM)","journal":"Cell cycle (Georgetown, Tex.)","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro reconstitution with mutagenesis, FRAP, and structural EM imaging in single lab (PMID:33208041); multiple orthogonal methods","pmids":["33208041"],"is_preprint":false},{"year":2022,"finding":"The APC/C ubiquitin ligase localizes to centrosomes specifically during mitosis, requires CEP152 for this centrosomal recruitment, ubiquitylates CEP152 as a substrate, and thereby releases CEP57 from the inhibitory CEP152-CEP57-CEP63 complex, enabling CEP57 to interact with pericentrin and promote microtubule nucleation.","method":"Co-IP identifying CEP152 as APC/C interaction partner and substrate; functional assays showing APC/C-mediated ubiquitylation of CEP152; immunofluorescence of CEP57-pericentrin interaction upon CEP152 degradation","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP and ubiquitylation assay with functional spindle readout in single lab (PMID:34878135); two orthogonal methods","pmids":["34878135"],"is_preprint":false},{"year":2023,"finding":"At nanoscale resolution, CEP152 (the major PLK4 receptor) develops a complex, non-nine-fold-symmetric pattern at mature centrioles, distinct from CEP57, CEP63, CEP44, and CEP192 which retain ninefold symmetry. This molecular arrangement of CEP152 creates flexibility for PLK4 and procentriole placement, enabling procentrioles to form at variable positions relative to mother centriole microtubule triplets.","method":"Expansion microscopy and super-resolution fluorescence microscopy (U-ExM), quantitative positional mapping of CEP152, PLK4, and other centriole components","journal":"The Journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — high-resolution nanoscale localization with quantitative positional analysis in single lab (PMID:37707473); single method but rigorous imaging approach","pmids":["37707473"],"is_preprint":false},{"year":2025,"finding":"Binding of the N-terminal part of CEP152 to PLK4 increases PLK4 phosphorylation and kinase activation, likely by stabilizing PLK4 dimer formation to promote autophosphorylation. CEP152 degradation disrupts PLK4 localization at the proximal centriole end and reduces phosphorylated PLK4 levels there.","method":"Auxin-inducible degron (AID) system for rapid CEP152 degradation in engineered cell lines; kinase activity assays; immunofluorescence for phospho-PLK4","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro kinase assay with defined domain constructs plus controlled cell-based degradation system (PMID:40372713); single lab, no mutagenesis validation of interaction interface","pmids":["40372713"],"is_preprint":false},{"year":2025,"finding":"PLK4 homodimerization via its CPB is required to maintain CEP152 at S-phase centrosomes; a cancer-associated PLK4 truncation mutation disrupting the CPB prevents PLK4 homodimerization, abrogates CEP152 and CEP192 interaction, reduces centrosomal CEP152 and pericentrin, and causes unfocused spindles and reduced cell viability.","method":"Cancer variant characterization, Co-IP of PLK4 mutants with CEP152/CEP192, immunofluorescence, cell viability assay","journal":"Journal of molecular biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP plus functional spindle and viability readouts in single lab (PMID:40222413); two orthogonal methods","pmids":["40222413"],"is_preprint":false},{"year":2025,"finding":"CEP152, CEP63, and PCNT form aggregates (cartwheel seeds, CSs) that act as seeds for cartwheel assembly independently of centrioles; these CSs form in interphase as nanoscale concentric rings of CEP152 and CEP63, recruit ALMS1 upon mitotic entry, and disassemble under ALMS1 control. ALMS1 depletion abolishes CS formation and eliminates centrioles.","method":"Super-resolution microscopy (U-ExM, SIM), TurboID proximity labeling, Co-IP, ALMS1 depletion/rescue experiments, immunofluorescence of centriole markers","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — preprint with multiple imaging methods and proximity proteomics but not yet peer-reviewed (PMID:40667363 / bio_10.1101_2025.06.26.661604)","pmids":["40667363"],"is_preprint":true},{"year":2022,"finding":"CEP152 is expressed in the centrosome of neuronal progenitors in the ventricular zone during embryonic brain development (E14) and also localizes to excitatory postsynaptic sites (co-localizing with PSD95 and synaptophysin) in differentiated hippocampal neurons, suggesting a role beyond centriole duplication in differentiated neurons.","method":"Immunohistochemistry, subcellular fractionation (postsynaptic density fraction), immunofluorescence co-localization in primary cultured hippocampal neurons","journal":"Developmental neuroscience","confidence":"Low","confidence_rationale":"Tier 3 / Weak — localization data without functional loss-of-function validation at synaptic sites (PMID:35259752); single lab, single method per finding","pmids":["35259752"],"is_preprint":false},{"year":2026,"finding":"Distinct CEP152 variant classes disrupt centriole function by different mechanisms: the p.K897* variant prevents centrosomal localization of CEP152, p.W105* leads to protein degradation, and p.Q32P retains centrosomal targeting but specifically disrupts binding to PLK4, causing centrosome structural abnormalities and mitotic errors in knock-in mouse brains.","method":"In vitro localization assays of mutant CEP152 constructs, Co-IP for PLK4 binding, knock-in mouse models with cortical phenotype analysis, electron microscopy of centriole structure, immunofluorescence for mitotic errors","journal":"EMBO molecular medicine","confidence":"High","confidence_rationale":"Tier 1 / Moderate — multiple orthogonal methods including in vitro mutagenesis, Co-IP, knock-in mouse models, and electron microscopy structural validation in single study (PMID:42086905)","pmids":["42086905"],"is_preprint":false},{"year":2026,"finding":"NuSAP localizes to centrioles and directly interacts with CEP57; NuSAP depletion disrupts centriole tubulin architecture and prevents recruitment of the CEP57-CEP63-CEP152 torus complex to the proximal end of procentrioles, establishing a two-step model where NuSAP-dependent tubulin stabilization is required for initial CEP57 loading upstream of CEP152 torus assembly.","method":"Super-resolution microscopy, TurboID-based proximity proteomics, Co-IP of NuSAP with CEP57, siRNA depletion with immunofluorescence readout","journal":"Advanced science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — proximity proteomics plus reciprocal Co-IP and functional depletion in single lab (PMID:41616107); multiple orthogonal methods","pmids":["41616107"],"is_preprint":false}],"current_model":"CEP152 is a pericentriolar scaffold protein that localizes to the proximal end of centrioles as part of a ring-like CEP57-CEP63-CEP152 torus complex; it recruits PLK4 to centrosomes via electrostatic interactions between its negatively charged N-terminal domain (residues 1–46) and PLK4's cryptic polo-box, and directly activates PLK4 kinase activity through this interaction to initiate centriole duplication once per cell cycle. CEP152 centrosomal localization depends on upstream CEP192 (and NuSAP-stabilized CEP57), while CEP152 itself is required for CPAP recruitment and is ubiquitylated by the APC/C during mitosis to release CEP57 and promote spindle assembly; the CEP63•CEP152 complex can also undergo liquid-liquid phase separation via hydrophobic motifs to form higher-order assemblies, and loss-of-function causes microcephaly and Seckel syndrome through centrosome dysfunction, mitotic errors, and enhanced ATM-mediated DNA damage signaling."},"narrative":{"mechanistic_narrative":"CEP152 is a pericentriolar scaffold protein that functions as the principal receptor coupling PLK4 to centrioles to license centriole duplication once per cell cycle [PMID:21059844, PMID:21059850, PMID:23641073, PMID:24277814]. It localizes around the proximal end of centrioles as part of a ring-like CEP57-CEP63-CEP152 torus [PMID:23333316], whose assembly requires upstream CEP192 for CEP152 recruitment and NuSAP-dependent tubulin stabilization for initial CEP57 loading [PMID:23641073, PMID:24277814, PMID:41616107]. CEP152 captures PLK4 through electrostatic engagement of its acidic N-terminal segment (residues 1–46) with PLK4's cryptic polo-box, an interaction that hands PLK4 off from CEP192 in a temporally and spatially staged manner and is required for PLK4 recruitment, CPAP loading, and procentriole formation [PMID:21059844, PMID:21059850, PMID:23641073, PMID:24277814]. Beyond tethering, CEP152 binding stimulates PLK4 kinase activity by promoting PLK4 dimerization and autophosphorylation, while reciprocal PLK4 homodimerization maintains CEP152 at S-phase centrosomes [PMID:40372713, PMID:40222413], and CEP152 is itself a PLK4 substrate [PMID:21059850]. CEP152 displays a non-ninefold-symmetric nanoscale arrangement that affords flexibility in procentriole placement [PMID:37707473], and the CEP63•CEP152 complex undergoes liquid-liquid phase separation via hydrophobic motifs to build higher-order centrosomal assemblies [PMID:33208041]. During mitosis CEP152 is ubiquitylated by the centrosome-localized APC/C, releasing CEP57 from the inhibitory torus to engage pericentrin and promote microtubule nucleation [PMID:34878135]. CEP152 loss-of-function causes microcephaly and Seckel syndrome, acting through centrosome dysfunction, mitotic errors, and enhanced ATM-mediated DNA damage signaling, with distinct patient variants disrupting localization, stability, or PLK4 binding [PMID:21131973, PMID:42086905].","teleology":[{"year":2008,"claim":"Established CEP152 as an early, conserved factor in centriole duplication rather than a structural centriole component, defining the biological process it serves.","evidence":"Loss-of-function in Drosophila (Asterless/mecD) and zebrafish morpholino knockdown with centriole marker immunolocalization and vertebrate rescue","pmids":["18854586"],"confidence":"Medium","gaps":["Did not define molecular partners or recruitment hierarchy","Mechanism of action at the centriole wall unresolved"]},{"year":2010,"claim":"Identified CEP152 as the PLK4 receptor and a recruiter of CPAP, placing it mechanistically at the initiation of centriole duplication.","evidence":"Co-IP and domain mapping of CEP152(1-217)–PLK4 cryptic polo-box, mislocalization assays, siRNA depletion with centriole/spindle readouts, and in vitro kinase assay","pmids":["21059844","21059850"],"confidence":"High","gaps":["Phosphorylation sites on CEP152 not mapped by mutagenesis","CPAP recruitment not independently replicated"]},{"year":2010,"claim":"Linked CEP152 loss to human Seckel syndrome and a genome-maintenance defect, connecting centrosome dysfunction to DNA damage signaling and tissue phenotype.","evidence":"Homozygosity mapping/exome sequencing of patients, truncation localization construct, and ATM/H2AX phosphorylation assays in patient cells","pmids":["21131973","20598275"],"confidence":"Medium","gaps":["Causal chain from centrosome defect to ATM activation not fully resolved","C-terminal targeting determinant only coarsely mapped"]},{"year":2013,"claim":"Resolved the recruitment hierarchy and architecture: CEP192 acts upstream of CEP152, both compete for PLK4 via homologous acidic N-terminal motifs, and CEP152 sits in a ring-like CEP57-CEP63-CEP152 torus.","evidence":"Sequential siRNA double-depletion, domain-deletion mapping, biochemical competition assays, chemical crosslinking, and STED super-resolution microscopy","pmids":["23641073","24277814","23333316"],"confidence":"High","gaps":["Temporal handoff mechanism between CEP192 and CEP152 not kinetically defined","Stoichiometry of the torus not established"]},{"year":2018,"claim":"Showed CEP152 behavior at acentriolar MTOCs is CDK1-regulated, extending its role to meiotic spindle organization.","evidence":"Staged mouse oocyte live imaging and immunofluorescence with siRNA depletion and CDK1 inhibition","pmids":["28970258"],"confidence":"Medium","gaps":["Direct CDK1 phosphorylation of CEP152 not demonstrated","Single system, single lab"]},{"year":2020,"claim":"Demonstrated that CEP63•CEP152 forms phase-separating condensates, providing a biophysical basis for higher-order centrosomal assembly.","evidence":"In vitro reconstitution of purified complex, FRAP, hexanediol treatment, hydrophobic-motif mutagenesis, and CLEM","pmids":["33208041"],"confidence":"High","gaps":["In vivo functional consequence of LLPS for PLK4 recruitment not directly tested","Hexanediol effects are non-specific"]},{"year":2022,"claim":"Revealed mitotic regulation of CEP152 by APC/C-mediated ubiquitylation, coupling its degradation to CEP57 release and microtubule nucleation.","evidence":"Co-IP, ubiquitylation assays, and immunofluorescence of CEP57-pericentrin interaction upon CEP152 degradation","pmids":["34878135"],"confidence":"Medium","gaps":["Ubiquitylation sites not mapped","Not independently replicated"]},{"year":2023,"claim":"Mapped CEP152 at nanoscale to a non-ninefold-symmetric pattern distinct from other torus components, explaining flexible procentriole placement.","evidence":"U-ExM expansion and super-resolution microscopy with quantitative positional mapping","pmids":["37707473"],"confidence":"Medium","gaps":["Functional consequence of asymmetry not perturbed","Single imaging method"]},{"year":2025,"claim":"Established that CEP152 binding actively stimulates PLK4 kinase activity and that PLK4 homodimerization reciprocally retains CEP152, defining a mutually reinforcing activation loop.","evidence":"Auxin-inducible degron degradation, kinase assays, phospho-PLK4 immunofluorescence, and Co-IP of cancer-associated PLK4 CPB mutants with viability/spindle readouts","pmids":["40372713","40222413"],"confidence":"Medium","gaps":["Interaction interface not validated by mutagenesis","Mechanism of dimer stabilization inferred indirectly"]},{"year":2026,"claim":"Showed distinct CEP152 patient variant classes disrupt centriole function by separable mechanisms (localization, stability, PLK4 binding) with cortical phenotypes in vivo.","evidence":"Mutant localization assays, Co-IP for PLK4 binding, knock-in mouse cortical analysis, and electron microscopy of centriole structure","pmids":["42086905"],"confidence":"High","gaps":["Genotype-phenotype correlation across human variants not exhaustive","Synaptic role of CEP152 (idx 16) not functionally validated"]},{"year":2026,"claim":"Placed NuSAP-dependent tubulin stabilization upstream of CEP57 loading, refining the assembly order of the CEP152-containing torus on procentrioles.","evidence":"Super-resolution microscopy, TurboID proximity proteomics, NuSAP-CEP57 Co-IP, and siRNA depletion","pmids":["41616107"],"confidence":"Medium","gaps":["Direct effect of NuSAP on CEP152 not separated from CEP57 effect","Single lab"]},{"year":null,"claim":"How the structural/biophysical states of CEP152 (LLPS condensates, asymmetric nanopattern, torus stoichiometry) are integrated with cell-cycle-controlled PLK4 activation and APC/C-mediated turnover to ensure exactly one duplication event remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of the CEP152-PLK4 active complex","Quantitative coupling of phase separation to PLK4 activation untested","Non-centriolar (synaptic) function uncharacterized functionally"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,6,7]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[13,14]},{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[8,10]}],"localization":[{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[5,8,12]}],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[0,1,11]},{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[5,8,18]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[3,17]}],"complexes":["CEP57-CEP63-CEP152 torus complex","CEP63•CEP152 heterotetramer"],"partners":["PLK4","CEP192","CEP63","CEP57","CPAP","APC/C","NUSAP","PCNT"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"O94986","full_name":"Centrosomal protein of 152 kDa","aliases":[],"length_aa":1710,"mass_kda":195.6,"function":"Necessary for centrosome duplication; the function also seems to involve CEP63, CDK5RAP2 and WDR62 through a stepwise assembled complex at the centrosome that recruits CDK2 required for centriole duplication (PubMed:26297806). Acts as a molecular scaffold facilitating the interaction of PLK4 and CPAP, 2 molecules involved in centriole formation (PubMed:20852615, PubMed:21059844). Proposed to snatch PLK4 away from PLK4:CEP92 complexes in early G1 daughter centriole and to reposition PLK4 at the outer boundary of a newly forming CEP152 ring structure (PubMed:24997597). Also plays a key role in deuterosome-mediated centriole amplification in multiciliated that can generate more than 100 centrioles (By similarity). Overexpression of CEP152 can drive amplification of centrioles (PubMed:20852615)","subcellular_location":"Cytoplasm, cytoskeleton, microtubule organizing center, centrosome; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole","url":"https://www.uniprot.org/uniprotkb/O94986/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CEP152","classification":"Not Classified","n_dependent_lines":249,"n_total_lines":1208,"dependency_fraction":0.20612582781456953},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/CEP152","total_profiled":1310},"omim":[{"mim_id":"621412","title":"CENTROSOMAL PROTEIN 57-LIKE 1; CEP57L1","url":"https://www.omim.org/entry/621412"},{"mim_id":"620217","title":"CENTROSOMAL PROTEIN, 44-KD; CEP44","url":"https://www.omim.org/entry/620217"},{"mim_id":"616426","title":"CENTROSOMAL PROTEIN, 192-KD; CEP192","url":"https://www.omim.org/entry/616426"},{"mim_id":"615587","title":"NUCLEOPORIN, 188-KD; NUP188","url":"https://www.omim.org/entry/615587"},{"mim_id":"614852","title":"MICROCEPHALY 9, PRIMARY, AUTOSOMAL RECESSIVE; MCPH9","url":"https://www.omim.org/entry/614852"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Centrosome","reliability":"Supported"},{"location":"Basal body","reliability":"Supported"},{"location":"Nucleoplasm","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"bone marrow","ntpm":15.5}],"url":"https://www.proteinatlas.org/search/CEP152"},"hgnc":{"alias_symbol":["KIAA0912","SCKL5","MCPH9"],"prev_symbol":[]},"alphafold":{"accession":"O94986","domains":[{"cath_id":"1.20.5","chopping":"237-349","consensus_level":"medium","plddt":88.8221,"start":237,"end":349}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O94986","model_url":"https://alphafold.ebi.ac.uk/files/AF-O94986-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O94986-F1-predicted_aligned_error_v6.png","plddt_mean":60.53},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CEP152","jax_strain_url":"https://www.jax.org/strain/search?query=CEP152"},"sequence":{"accession":"O94986","fasta_url":"https://rest.uniprot.org/uniprotkb/O94986.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O94986/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O94986"}},"corpus_meta":[{"pmid":"21059844","id":"PMC_21059844","title":"Cep152 acts as a scaffold for recruitment of Plk4 and CPAP to the centrosome.","date":"2010","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/21059844","citation_count":233,"is_preprint":false},{"pmid":"21059850","id":"PMC_21059850","title":"Cep152 interacts with Plk4 and is required for centriole duplication.","date":"2010","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/21059850","citation_count":230,"is_preprint":false},{"pmid":"23641073","id":"PMC_23641073","title":"Human Cep192 and Cep152 cooperate in Plk4 recruitment and centriole duplication.","date":"2013","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/23641073","citation_count":196,"is_preprint":false},{"pmid":"21131973","id":"PMC_21131973","title":"CEP152 is a genome maintenance protein disrupted in Seckel syndrome.","date":"2010","source":"Nature genetics","url":"https://pubmed.ncbi.nlm.nih.gov/21131973","citation_count":180,"is_preprint":false},{"pmid":"24277814","id":"PMC_24277814","title":"Hierarchical recruitment of Plk4 and regulation of centriole biogenesis by two centrosomal scaffolds, Cep192 and Cep152.","date":"2013","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/24277814","citation_count":178,"is_preprint":false},{"pmid":"20598275","id":"PMC_20598275","title":"Mutations in centrosomal protein CEP152 in primary microcephaly families linked to MCPH4.","date":"2010","source":"American journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/20598275","citation_count":148,"is_preprint":false},{"pmid":"18854586","id":"PMC_18854586","title":"Drosophila asterless and vertebrate Cep152 Are orthologs essential for centriole duplication.","date":"2008","source":"Genetics","url":"https://pubmed.ncbi.nlm.nih.gov/18854586","citation_count":136,"is_preprint":false},{"pmid":"23333316","id":"PMC_23333316","title":"Selective chemical crosslinking reveals a Cep57-Cep63-Cep152 centrosomal complex.","date":"2013","source":"Current biology : CB","url":"https://pubmed.ncbi.nlm.nih.gov/23333316","citation_count":100,"is_preprint":false},{"pmid":"28970258","id":"PMC_28970258","title":"Distinct roles of Cep192 and Cep152 in acentriolar MTOCs and spindle formation during mouse oocyte maturation.","date":"2018","source":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology","url":"https://pubmed.ncbi.nlm.nih.gov/28970258","citation_count":23,"is_preprint":false},{"pmid":"33208041","id":"PMC_33208041","title":"Phase separation of the Cep63•Cep152 complex underlies the formation of dynamic supramolecular self-assemblies at human centrosomes.","date":"2020","source":"Cell cycle 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England)","url":"https://pubmed.ncbi.nlm.nih.gov/34156311","citation_count":2,"is_preprint":false},{"pmid":"40222413","id":"PMC_40222413","title":"PLK4 Homodimerization is Required for CEP152 Centrosome Localization and Spindle Organization.","date":"2025","source":"Journal of molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/40222413","citation_count":1,"is_preprint":false},{"pmid":"38229970","id":"PMC_38229970","title":"Novel Variants of CEP152 in a Case of Compound-Heterozygous Inheritance of Epilepsy.","date":"2024","source":"Global medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/38229970","citation_count":0,"is_preprint":false},{"pmid":"40667363","id":"PMC_40667363","title":"Centriole biogenesis is seeded by CEP152-CEP63-PCNT aggregates propagating outside the centriole through the Alström syndrome protein ALMS1.","date":"2025","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/40667363","citation_count":0,"is_preprint":false},{"pmid":"42086905","id":"PMC_42086905","title":"Distinct pathophysiological mechanisms of CEP152 variants in microcephaly and brain abnormalities.","date":"2026","source":"EMBO molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/42086905","citation_count":0,"is_preprint":false},{"pmid":"41306914","id":"PMC_41306914","title":"Case Report: Compound heterozygous CEP152 c.3346-5T>C variant and chr15 deletion causing recurrent MCPH-SCKS in a Chinese pregnant woman across two consecutive pregnancies.","date":"2025","source":"Frontiers in genetics","url":"https://pubmed.ncbi.nlm.nih.gov/41306914","citation_count":0,"is_preprint":false},{"pmid":"41616107","id":"PMC_41616107","title":"NuSAP Safeguards Centriole Integrity to Mediate CEP57-CEP152 Torus Recruitment for Proper Engagement.","date":"2026","source":"Advanced science (Weinheim, Baden-Wurttemberg, Germany)","url":"https://pubmed.ncbi.nlm.nih.gov/41616107","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.06.26.661604","title":"Adaptable centriole biogenesis via the intrinsically disordered protein ALMS1","date":"2025-06-27","source":"bioRxiv","url":"https://doi.org/10.1101/2025.06.26.661604","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.10.28.620588","title":"Interactions of N- and C-terminal parts of Ana1 permitting centriole duplication but not elongation","date":"2024-10-31","source":"bioRxiv","url":"https://doi.org/10.1101/2024.10.28.620588","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":13225,"output_tokens":5033,"usd":0.057585,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":13208,"output_tokens":3872,"usd":0.08142,"stage2_stop_reason":"end_turn"},"total_usd":0.139005,"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\": 2010,\n      \"finding\": \"CEP152 interacts with the cryptic Polo-box (CPB) of PLK4 via its N-terminal domain (first 217 residues), and this interaction is required for PLK4 recruitment to centrosomes and for PLK4-induced centriole overduplication.\",\n      \"method\": \"Co-immunoprecipitation, overexpression of truncated CEP152(1-217) to mislocalize PLK4, siRNA knockdown with centriole duplication readout\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — two independent labs (PMID:21059844 and PMID:21059850) using reciprocal Co-IP, domain-mapping, and loss-of-function with orthogonal readouts, replicated in the same year\",\n      \"pmids\": [\"21059844\", \"21059850\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"CEP152 is required for recruitment of CPAP to the centrosome; depletion of CEP152 causes loss of CPAP, monopolar mitotic spindles, and failure of centriole duplication.\",\n      \"method\": \"siRNA knockdown, immunofluorescence for CPAP and centriole markers, spindle formation assay\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — single lab (PMID:21059844), clean knockdown with defined phenotypic readouts but not independently replicated for CPAP specifically\",\n      \"pmids\": [\"21059844\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"CEP152 can be phosphorylated by PLK4 in vitro, indicating CEP152 is a PLK4 substrate.\",\n      \"method\": \"In vitro kinase assay with recombinant PLK4 and CEP152\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — direct in vitro kinase assay in single lab (PMID:21059850); not yet confirmed with mutagenesis of phosphorylation sites\",\n      \"pmids\": [\"21059850\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"CEP152 loss-of-function leads to accumulation of genomic defects through replicative stress, enhanced ATM signaling activation, and increased H2AX phosphorylation, identifying CEP152 as a genome maintenance/DNA damage response regulator.\",\n      \"method\": \"Homozygosity mapping and exome sequencing to identify CEP152 mutations in Seckel syndrome; functional assays measuring ATM signaling and H2AX phosphorylation in patient-derived cells\",\n      \"journal\": \"Nature genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — patient genetics plus cellular functional assays in single lab (PMID:21131973); two orthogonal readouts (ATM activation, H2AX phosphorylation)\",\n      \"pmids\": [\"21131973\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"A CEP152 truncation mutation that removes one-third of the protein prevents its localization to centrosomes, demonstrating that the C-terminal region is required for centrosomal targeting.\",\n      \"method\": \"Transfection of truncated CEP152 construct in cells, immunofluorescence microscopy\",\n      \"journal\": \"American journal of human genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — direct localization experiment with defined construct in single study (PMID:20598275)\",\n      \"pmids\": [\"20598275\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"CEP152 (vertebrate ortholog of Drosophila Asterless/Asl) is essential for daughter centriole formation; depletion eliminates multiple centriolar markers while only mildly affecting pericentriolar material (PCM) function, placing CEP152 early in centriole duplication. CEP152/Asl localizes closely associated with the centriole wall but is not part of the centriole structure itself.\",\n      \"method\": \"Loss-of-function allele characterization in Drosophila (mecD asl allele), morpholino knockdown in zebrafish, immunolocalization of centriole markers and PCM components\",\n      \"journal\": \"Genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multi-organism (Drosophila + zebrafish), multiple centriole markers analyzed, functional rescue with vertebrate Cep152 (PMID:18854586)\",\n      \"pmids\": [\"18854586\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"CEP192 and CEP152 cooperate to recruit PLK4 to mammalian centrioles: CEP192 is required for centrosomal recruitment of CEP152 (placing CEP192 upstream), and double-depletion of both proteins completely abolishes PLK4 binding and centriole duplication. PLK4 binding regions of CEP192 and CEP152 (residues 190–240 and 1–46, respectively) are rich in negatively charged amino acids, suggesting electrostatic interactions with PLK4's positively charged polo-box domain.\",\n      \"method\": \"Sequential siRNA double-depletion, Co-IP, domain-deletion mapping, super-resolution microscopy\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — replicated by two independent labs in the same year (PMID:23641073 and PMID:24277814) with reciprocal Co-IP, domain mapping, and epistasis experiments\",\n      \"pmids\": [\"23641073\", \"24277814\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"CEP192 and CEP152 serve as two distinct hierarchical scaffolds that recruit PLK4 to distinct subcentrosomal regions in a temporally regulated manner; CEP192 and CEP152 competitively interact with the cryptic polo-box of PLK4 through homologous N-terminal sequences containing acidic-α-helix and N/Q-rich motifs. Expression of either N-terminal fragment alone is sufficient to delocalize PLK4 from centrosomes.\",\n      \"method\": \"Biochemical competition assays, Co-IP with truncated constructs, live-cell imaging, loss-of-function by depletion with centriole duplication readout\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — PMID:24277814, multiple orthogonal methods (Co-IP, domain mapping, competition assay, live imaging, depletion epistasis), corroborated by PMID:23641073\",\n      \"pmids\": [\"24277814\", \"23641073\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"CEP57, CEP63, and CEP152 form a ring-like complex localizing around the proximal end of centrioles, as revealed by selective chemical crosslinking and super-resolution microscopy. CEP152 and PLK4 reside in two separable structures at the centrosome, suggesting PLK4 contacts CEP152 only transiently.\",\n      \"method\": \"Selective chemical crosslinking (SNAP-tag-based), super-resolution (STED) microscopy, pulldown assays\",\n      \"journal\": \"Current biology : CB\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — chemical crosslinking combined with super-resolution imaging and biochemical assays in single lab (PMID:23333316); orthogonal structural and biochemical methods\",\n      \"pmids\": [\"23333316\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"In mouse oocytes (acentriolar MTOCs), CEP152 localizes to MTOCs at the germinal vesicle stage and is excluded from MTOCs after germinal vesicle breakdown; this exclusion is regulated by CDK1 activity and is involved in MTOC fragmentation during meiotic spindle formation.\",\n      \"method\": \"Live-cell imaging, immunofluorescence of staged oocytes, siRNA depletion with CDK1 inhibitor treatment and MTOC/spindle morphology readouts\",\n      \"journal\": \"FASEB journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization with CDK1 inhibitor functional test in mouse oocytes (PMID:28970258); two orthogonal approaches but single lab\",\n      \"pmids\": [\"28970258\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"CEP63 and CEP152 cooperatively form a heterotetrameric complex that undergoes liquid-liquid phase separation (LLPS) to generate higher-order self-assemblies at centrosomes. Two hydrophobic motifs, one each from CEP63 and CEP152, are required for phase-separating condensates and high-molecular-weight assembly. LLPS disruptor 1,6-hexanediol diminishes endogenous CEP63 and CEP152 centrosome localization.\",\n      \"method\": \"In vitro reconstitution of purified CEP63•CEP152 complex, FRAP, hexanediol treatment, mutagenesis of hydrophobic motifs, correlative light-electron microscopy (CLEM)\",\n      \"journal\": \"Cell cycle (Georgetown, Tex.)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro reconstitution with mutagenesis, FRAP, and structural EM imaging in single lab (PMID:33208041); multiple orthogonal methods\",\n      \"pmids\": [\"33208041\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"The APC/C ubiquitin ligase localizes to centrosomes specifically during mitosis, requires CEP152 for this centrosomal recruitment, ubiquitylates CEP152 as a substrate, and thereby releases CEP57 from the inhibitory CEP152-CEP57-CEP63 complex, enabling CEP57 to interact with pericentrin and promote microtubule nucleation.\",\n      \"method\": \"Co-IP identifying CEP152 as APC/C interaction partner and substrate; functional assays showing APC/C-mediated ubiquitylation of CEP152; immunofluorescence of CEP57-pericentrin interaction upon CEP152 degradation\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP and ubiquitylation assay with functional spindle readout in single lab (PMID:34878135); two orthogonal methods\",\n      \"pmids\": [\"34878135\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"At nanoscale resolution, CEP152 (the major PLK4 receptor) develops a complex, non-nine-fold-symmetric pattern at mature centrioles, distinct from CEP57, CEP63, CEP44, and CEP192 which retain ninefold symmetry. This molecular arrangement of CEP152 creates flexibility for PLK4 and procentriole placement, enabling procentrioles to form at variable positions relative to mother centriole microtubule triplets.\",\n      \"method\": \"Expansion microscopy and super-resolution fluorescence microscopy (U-ExM), quantitative positional mapping of CEP152, PLK4, and other centriole components\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — high-resolution nanoscale localization with quantitative positional analysis in single lab (PMID:37707473); single method but rigorous imaging approach\",\n      \"pmids\": [\"37707473\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Binding of the N-terminal part of CEP152 to PLK4 increases PLK4 phosphorylation and kinase activation, likely by stabilizing PLK4 dimer formation to promote autophosphorylation. CEP152 degradation disrupts PLK4 localization at the proximal centriole end and reduces phosphorylated PLK4 levels there.\",\n      \"method\": \"Auxin-inducible degron (AID) system for rapid CEP152 degradation in engineered cell lines; kinase activity assays; immunofluorescence for phospho-PLK4\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro kinase assay with defined domain constructs plus controlled cell-based degradation system (PMID:40372713); single lab, no mutagenesis validation of interaction interface\",\n      \"pmids\": [\"40372713\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"PLK4 homodimerization via its CPB is required to maintain CEP152 at S-phase centrosomes; a cancer-associated PLK4 truncation mutation disrupting the CPB prevents PLK4 homodimerization, abrogates CEP152 and CEP192 interaction, reduces centrosomal CEP152 and pericentrin, and causes unfocused spindles and reduced cell viability.\",\n      \"method\": \"Cancer variant characterization, Co-IP of PLK4 mutants with CEP152/CEP192, immunofluorescence, cell viability assay\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP plus functional spindle and viability readouts in single lab (PMID:40222413); two orthogonal methods\",\n      \"pmids\": [\"40222413\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CEP152, CEP63, and PCNT form aggregates (cartwheel seeds, CSs) that act as seeds for cartwheel assembly independently of centrioles; these CSs form in interphase as nanoscale concentric rings of CEP152 and CEP63, recruit ALMS1 upon mitotic entry, and disassemble under ALMS1 control. ALMS1 depletion abolishes CS formation and eliminates centrioles.\",\n      \"method\": \"Super-resolution microscopy (U-ExM, SIM), TurboID proximity labeling, Co-IP, ALMS1 depletion/rescue experiments, immunofluorescence of centriole markers\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — preprint with multiple imaging methods and proximity proteomics but not yet peer-reviewed (PMID:40667363 / bio_10.1101_2025.06.26.661604)\",\n      \"pmids\": [\"40667363\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"CEP152 is expressed in the centrosome of neuronal progenitors in the ventricular zone during embryonic brain development (E14) and also localizes to excitatory postsynaptic sites (co-localizing with PSD95 and synaptophysin) in differentiated hippocampal neurons, suggesting a role beyond centriole duplication in differentiated neurons.\",\n      \"method\": \"Immunohistochemistry, subcellular fractionation (postsynaptic density fraction), immunofluorescence co-localization in primary cultured hippocampal neurons\",\n      \"journal\": \"Developmental neuroscience\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — localization data without functional loss-of-function validation at synaptic sites (PMID:35259752); single lab, single method per finding\",\n      \"pmids\": [\"35259752\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"Distinct CEP152 variant classes disrupt centriole function by different mechanisms: the p.K897* variant prevents centrosomal localization of CEP152, p.W105* leads to protein degradation, and p.Q32P retains centrosomal targeting but specifically disrupts binding to PLK4, causing centrosome structural abnormalities and mitotic errors in knock-in mouse brains.\",\n      \"method\": \"In vitro localization assays of mutant CEP152 constructs, Co-IP for PLK4 binding, knock-in mouse models with cortical phenotype analysis, electron microscopy of centriole structure, immunofluorescence for mitotic errors\",\n      \"journal\": \"EMBO molecular medicine\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — multiple orthogonal methods including in vitro mutagenesis, Co-IP, knock-in mouse models, and electron microscopy structural validation in single study (PMID:42086905)\",\n      \"pmids\": [\"42086905\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"NuSAP localizes to centrioles and directly interacts with CEP57; NuSAP depletion disrupts centriole tubulin architecture and prevents recruitment of the CEP57-CEP63-CEP152 torus complex to the proximal end of procentrioles, establishing a two-step model where NuSAP-dependent tubulin stabilization is required for initial CEP57 loading upstream of CEP152 torus assembly.\",\n      \"method\": \"Super-resolution microscopy, TurboID-based proximity proteomics, Co-IP of NuSAP with CEP57, siRNA depletion with immunofluorescence readout\",\n      \"journal\": \"Advanced science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — proximity proteomics plus reciprocal Co-IP and functional depletion in single lab (PMID:41616107); multiple orthogonal methods\",\n      \"pmids\": [\"41616107\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CEP152 is a pericentriolar scaffold protein that localizes to the proximal end of centrioles as part of a ring-like CEP57-CEP63-CEP152 torus complex; it recruits PLK4 to centrosomes via electrostatic interactions between its negatively charged N-terminal domain (residues 1–46) and PLK4's cryptic polo-box, and directly activates PLK4 kinase activity through this interaction to initiate centriole duplication once per cell cycle. CEP152 centrosomal localization depends on upstream CEP192 (and NuSAP-stabilized CEP57), while CEP152 itself is required for CPAP recruitment and is ubiquitylated by the APC/C during mitosis to release CEP57 and promote spindle assembly; the CEP63•CEP152 complex can also undergo liquid-liquid phase separation via hydrophobic motifs to form higher-order assemblies, and loss-of-function causes microcephaly and Seckel syndrome through centrosome dysfunction, mitotic errors, and enhanced ATM-mediated DNA damage signaling.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CEP152 is a pericentriolar scaffold protein that functions as the principal receptor coupling PLK4 to centrioles to license centriole duplication once per cell cycle [#0, #6]. It localizes around the proximal end of centrioles as part of a ring-like CEP57-CEP63-CEP152 torus [#8], whose assembly requires upstream CEP192 for CEP152 recruitment and NuSAP-dependent tubulin stabilization for initial CEP57 loading [#6, #18]. CEP152 captures PLK4 through electrostatic engagement of its acidic N-terminal segment (residues 1\\u201346) with PLK4's cryptic polo-box, an interaction that hands PLK4 off from CEP192 in a temporally and spatially staged manner and is required for PLK4 recruitment, CPAP loading, and procentriole formation [#0, #6, #7, #1]. Beyond tethering, CEP152 binding stimulates PLK4 kinase activity by promoting PLK4 dimerization and autophosphorylation, while reciprocal PLK4 homodimerization maintains CEP152 at S-phase centrosomes [#13, #14], and CEP152 is itself a PLK4 substrate [#2]. CEP152 displays a non-ninefold-symmetric nanoscale arrangement that affords flexibility in procentriole placement [#12], and the CEP63\\u2022CEP152 complex undergoes liquid-liquid phase separation via hydrophobic motifs to build higher-order centrosomal assemblies [#10]. During mitosis CEP152 is ubiquitylated by the centrosome-localized APC/C, releasing CEP57 from the inhibitory torus to engage pericentrin and promote microtubule nucleation [#11]. CEP152 loss-of-function causes microcephaly and Seckel syndrome, acting through centrosome dysfunction, mitotic errors, and enhanced ATM-mediated DNA damage signaling, with distinct patient variants disrupting localization, stability, or PLK4 binding [#3, #17].\",\n  \"teleology\": [\n    {\n      \"year\": 2008,\n      \"claim\": \"Established CEP152 as an early, conserved factor in centriole duplication rather than a structural centriole component, defining the biological process it serves.\",\n      \"evidence\": \"Loss-of-function in Drosophila (Asterless/mecD) and zebrafish morpholino knockdown with centriole marker immunolocalization and vertebrate rescue\",\n      \"pmids\": [\"18854586\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Did not define molecular partners or recruitment hierarchy\", \"Mechanism of action at the centriole wall unresolved\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Identified CEP152 as the PLK4 receptor and a recruiter of CPAP, placing it mechanistically at the initiation of centriole duplication.\",\n      \"evidence\": \"Co-IP and domain mapping of CEP152(1-217)\\u2013PLK4 cryptic polo-box, mislocalization assays, siRNA depletion with centriole/spindle readouts, and in vitro kinase assay\",\n      \"pmids\": [\"21059844\", \"21059850\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Phosphorylation sites on CEP152 not mapped by mutagenesis\", \"CPAP recruitment not independently replicated\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Linked CEP152 loss to human Seckel syndrome and a genome-maintenance defect, connecting centrosome dysfunction to DNA damage signaling and tissue phenotype.\",\n      \"evidence\": \"Homozygosity mapping/exome sequencing of patients, truncation localization construct, and ATM/H2AX phosphorylation assays in patient cells\",\n      \"pmids\": [\"21131973\", \"20598275\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Causal chain from centrosome defect to ATM activation not fully resolved\", \"C-terminal targeting determinant only coarsely mapped\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Resolved the recruitment hierarchy and architecture: CEP192 acts upstream of CEP152, both compete for PLK4 via homologous acidic N-terminal motifs, and CEP152 sits in a ring-like CEP57-CEP63-CEP152 torus.\",\n      \"evidence\": \"Sequential siRNA double-depletion, domain-deletion mapping, biochemical competition assays, chemical crosslinking, and STED super-resolution microscopy\",\n      \"pmids\": [\"23641073\", \"24277814\", \"23333316\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Temporal handoff mechanism between CEP192 and CEP152 not kinetically defined\", \"Stoichiometry of the torus not established\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Showed CEP152 behavior at acentriolar MTOCs is CDK1-regulated, extending its role to meiotic spindle organization.\",\n      \"evidence\": \"Staged mouse oocyte live imaging and immunofluorescence with siRNA depletion and CDK1 inhibition\",\n      \"pmids\": [\"28970258\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct CDK1 phosphorylation of CEP152 not demonstrated\", \"Single system, single lab\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Demonstrated that CEP63\\u2022CEP152 forms phase-separating condensates, providing a biophysical basis for higher-order centrosomal assembly.\",\n      \"evidence\": \"In vitro reconstitution of purified complex, FRAP, hexanediol treatment, hydrophobic-motif mutagenesis, and CLEM\",\n      \"pmids\": [\"33208041\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"In vivo functional consequence of LLPS for PLK4 recruitment not directly tested\", \"Hexanediol effects are non-specific\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Revealed mitotic regulation of CEP152 by APC/C-mediated ubiquitylation, coupling its degradation to CEP57 release and microtubule nucleation.\",\n      \"evidence\": \"Co-IP, ubiquitylation assays, and immunofluorescence of CEP57-pericentrin interaction upon CEP152 degradation\",\n      \"pmids\": [\"34878135\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Ubiquitylation sites not mapped\", \"Not independently replicated\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Mapped CEP152 at nanoscale to a non-ninefold-symmetric pattern distinct from other torus components, explaining flexible procentriole placement.\",\n      \"evidence\": \"U-ExM expansion and super-resolution microscopy with quantitative positional mapping\",\n      \"pmids\": [\"37707473\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequence of asymmetry not perturbed\", \"Single imaging method\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Established that CEP152 binding actively stimulates PLK4 kinase activity and that PLK4 homodimerization reciprocally retains CEP152, defining a mutually reinforcing activation loop.\",\n      \"evidence\": \"Auxin-inducible degron degradation, kinase assays, phospho-PLK4 immunofluorescence, and Co-IP of cancer-associated PLK4 CPB mutants with viability/spindle readouts\",\n      \"pmids\": [\"40372713\", \"40222413\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Interaction interface not validated by mutagenesis\", \"Mechanism of dimer stabilization inferred indirectly\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Showed distinct CEP152 patient variant classes disrupt centriole function by separable mechanisms (localization, stability, PLK4 binding) with cortical phenotypes in vivo.\",\n      \"evidence\": \"Mutant localization assays, Co-IP for PLK4 binding, knock-in mouse cortical analysis, and electron microscopy of centriole structure\",\n      \"pmids\": [\"42086905\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Genotype-phenotype correlation across human variants not exhaustive\", \"Synaptic role of CEP152 (idx 16) not functionally validated\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Placed NuSAP-dependent tubulin stabilization upstream of CEP57 loading, refining the assembly order of the CEP152-containing torus on procentrioles.\",\n      \"evidence\": \"Super-resolution microscopy, TurboID proximity proteomics, NuSAP-CEP57 Co-IP, and siRNA depletion\",\n      \"pmids\": [\"41616107\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct effect of NuSAP on CEP152 not separated from CEP57 effect\", \"Single lab\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How the structural/biophysical states of CEP152 (LLPS condensates, asymmetric nanopattern, torus stoichiometry) are integrated with cell-cycle-controlled PLK4 activation and APC/C-mediated turnover to ensure exactly one duplication event remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model of the CEP152-PLK4 active complex\", \"Quantitative coupling of phase separation to PLK4 activation untested\", \"Non-centriolar (synaptic) function uncharacterized functionally\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 6, 7]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [13, 14]},\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [8, 10]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [5, 8, 12]},\n      {\"term_id\": \"GO:0005813\", \"supporting_discovery_ids\": [0, 8]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [0, 1, 11]},\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [5, 8, 18]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [3, 17]}\n    ],\n    \"complexes\": [\n      \"CEP57-CEP63-CEP152 torus complex\",\n      \"CEP63\\u2022CEP152 heterotetramer\"\n    ],\n    \"partners\": [\n      \"PLK4\",\n      \"CEP192\",\n      \"CEP63\",\n      \"CEP57\",\n      \"CPAP\",\n      \"APC/C\",\n      \"NuSAP\",\n      \"PCNT\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}