Affinage

CEP152

Centrosomal protein of 152 kDa · UniProt O94986

Length
1710 aa
Mass
195.6 kDa
Annotated
2026-06-09
22 papers in source corpus 18 papers cited in narrative 19 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

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).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2008 Medium

    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

    PMID:18854586

    Open questions at the time
    • Did not define molecular partners or recruitment hierarchy
    • Mechanism of action at the centriole wall unresolved
  2. 2010 High

    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

    PMID:21059844 PMID:21059850

    Open questions at the time
    • Phosphorylation sites on CEP152 not mapped by mutagenesis
    • CPAP recruitment not independently replicated
  3. 2010 Medium

    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

    PMID:20598275 PMID:21131973

    Open questions at the time
    • Causal chain from centrosome defect to ATM activation not fully resolved
    • C-terminal targeting determinant only coarsely mapped
  4. 2013 High

    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

    PMID:23333316 PMID:23641073 PMID:24277814

    Open questions at the time
    • Temporal handoff mechanism between CEP192 and CEP152 not kinetically defined
    • Stoichiometry of the torus not established
  5. 2018 Medium

    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

    PMID:28970258

    Open questions at the time
    • Direct CDK1 phosphorylation of CEP152 not demonstrated
    • Single system, single lab
  6. 2020 High

    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

    PMID:33208041

    Open questions at the time
    • In vivo functional consequence of LLPS for PLK4 recruitment not directly tested
    • Hexanediol effects are non-specific
  7. 2022 Medium

    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

    PMID:34878135

    Open questions at the time
    • Ubiquitylation sites not mapped
    • Not independently replicated
  8. 2023 Medium

    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

    PMID:37707473

    Open questions at the time
    • Functional consequence of asymmetry not perturbed
    • Single imaging method
  9. 2025 Medium

    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

    PMID:40222413 PMID:40372713

    Open questions at the time
    • Interaction interface not validated by mutagenesis
    • Mechanism of dimer stabilization inferred indirectly
  10. 2026 High

    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

    PMID:42086905

    Open questions at the time
    • Genotype-phenotype correlation across human variants not exhaustive
    • Synaptic role of CEP152 (idx 16) not functionally validated
  11. 2026 Medium

    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

    PMID:41616107

    Open questions at the time
    • Direct effect of NuSAP on CEP152 not separated from CEP57 effect
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • 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.
  • 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

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0005198 structural molecule activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005815 microtubule organizing center 3
Pathway
R-HSA-1640170 Cell Cycle 3 R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-1643685 Disease 2
Complex memberships
CEP57-CEP63-CEP152 torus complexCEP63•CEP152 heterotetramer

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 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. Co-immunoprecipitation, overexpression of truncated CEP152(1-217) to mislocalize PLK4, siRNA knockdown with centriole duplication readout The Journal of cell biology High 21059844 21059850
2010 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. siRNA knockdown, immunofluorescence for CPAP and centriole markers, spindle formation assay The Journal of cell biology Medium 21059844
2010 CEP152 can be phosphorylated by PLK4 in vitro, indicating CEP152 is a PLK4 substrate. In vitro kinase assay with recombinant PLK4 and CEP152 The Journal of cell biology Medium 21059850
2010 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. Homozygosity mapping and exome sequencing to identify CEP152 mutations in Seckel syndrome; functional assays measuring ATM signaling and H2AX phosphorylation in patient-derived cells Nature genetics Medium 21131973
2010 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. Transfection of truncated CEP152 construct in cells, immunofluorescence microscopy American journal of human genetics Medium 20598275
2008 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. Loss-of-function allele characterization in Drosophila (mecD asl allele), morpholino knockdown in zebrafish, immunolocalization of centriole markers and PCM components Genetics Medium 18854586
2013 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. Sequential siRNA double-depletion, Co-IP, domain-deletion mapping, super-resolution microscopy Journal of cell science High 23641073 24277814
2013 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. Biochemical competition assays, Co-IP with truncated constructs, live-cell imaging, loss-of-function by depletion with centriole duplication readout Proceedings of the National Academy of Sciences of the United States of America High 23641073 24277814
2013 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. Selective chemical crosslinking (SNAP-tag-based), super-resolution (STED) microscopy, pulldown assays Current biology : CB High 23333316
2018 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. Live-cell imaging, immunofluorescence of staged oocytes, siRNA depletion with CDK1 inhibitor treatment and MTOC/spindle morphology readouts FASEB journal Medium 28970258
2020 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. In vitro reconstitution of purified CEP63•CEP152 complex, FRAP, hexanediol treatment, mutagenesis of hydrophobic motifs, correlative light-electron microscopy (CLEM) Cell cycle (Georgetown, Tex.) High 33208041
2022 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. 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 of cell science Medium 34878135
2023 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. Expansion microscopy and super-resolution fluorescence microscopy (U-ExM), quantitative positional mapping of CEP152, PLK4, and other centriole components The Journal of cell biology Medium 37707473
2025 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. Auxin-inducible degron (AID) system for rapid CEP152 degradation in engineered cell lines; kinase activity assays; immunofluorescence for phospho-PLK4 Molecular biology of the cell Medium 40372713
2025 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. Cancer variant characterization, Co-IP of PLK4 mutants with CEP152/CEP192, immunofluorescence, cell viability assay Journal of molecular biology Medium 40222413
2025 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. Super-resolution microscopy (U-ExM, SIM), TurboID proximity labeling, Co-IP, ALMS1 depletion/rescue experiments, immunofluorescence of centriole markers bioRxivpreprint Medium 40667363
2022 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. Immunohistochemistry, subcellular fractionation (postsynaptic density fraction), immunofluorescence co-localization in primary cultured hippocampal neurons Developmental neuroscience Low 35259752
2026 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. 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 EMBO molecular medicine High 42086905
2026 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. Super-resolution microscopy, TurboID-based proximity proteomics, Co-IP of NuSAP with CEP57, siRNA depletion with immunofluorescence readout Advanced science Medium 41616107

Source papers

Stage 0 corpus · 22 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Cep152 acts as a scaffold for recruitment of Plk4 and CPAP to the centrosome. The Journal of cell biology 233 21059844
2010 Cep152 interacts with Plk4 and is required for centriole duplication. The Journal of cell biology 230 21059850
2013 Human Cep192 and Cep152 cooperate in Plk4 recruitment and centriole duplication. Journal of cell science 196 23641073
2010 CEP152 is a genome maintenance protein disrupted in Seckel syndrome. Nature genetics 180 21131973
2013 Hierarchical recruitment of Plk4 and regulation of centriole biogenesis by two centrosomal scaffolds, Cep192 and Cep152. Proceedings of the National Academy of Sciences of the United States of America 178 24277814
2010 Mutations in centrosomal protein CEP152 in primary microcephaly families linked to MCPH4. American journal of human genetics 148 20598275
2008 Drosophila asterless and vertebrate Cep152 Are orthologs essential for centriole duplication. Genetics 136 18854586
2013 Selective chemical crosslinking reveals a Cep57-Cep63-Cep152 centrosomal complex. Current biology : CB 100 23333316
2018 Distinct roles of Cep192 and Cep152 in acentriolar MTOCs and spindle formation during mouse oocyte maturation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 23 28970258
2020 Phase separation of the Cep63•Cep152 complex underlies the formation of dynamic supramolecular self-assemblies at human centrosomes. Cell cycle (Georgetown, Tex.) 19 33208041
2022 The APC/C targets the Cep152-Cep63 complex at the centrosome to regulate mitotic spindle assembly. Journal of cell science 13 34878135
2023 Centrosomal organization of Cep152 provides flexibility in Plk4 and procentriole positioning. The Journal of cell biology 12 37707473
2022 Expression Analyses of Cep152, a Responsible Gene Product for Autosomal Recessive Primary Microcephaly, during Mouse Brain Development. Developmental neuroscience 5 35259752
2023 Two novel variants in CEP152 caused Seckel syndrome 5 in a Chinese family. Frontiers in genetics 3 36685824
2025 Binding of CEP152 to PLK4 stimulates kinase activity to promote centriole assembly. Molecular biology of the cell 2 40372713
2021 Polymorphism in miRNA target sites of CEP-63 and CEP-152 ring complex influences expression of CEP genes and favors tumorigenesis in glioma. Future oncology (London, England) 2 34156311
2025 PLK4 Homodimerization is Required for CEP152 Centrosome Localization and Spindle Organization. Journal of molecular biology 1 40222413
2026 NuSAP Safeguards Centriole Integrity to Mediate CEP57-CEP152 Torus Recruitment for Proper Engagement. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 41616107
2026 Distinct pathophysiological mechanisms of CEP152 variants in microcephaly and brain abnormalities. EMBO molecular medicine 0 42086905
2025 Centriole biogenesis is seeded by CEP152-CEP63-PCNT aggregates propagating outside the centriole through the Alström syndrome protein ALMS1. bioRxiv : the preprint server for biology 0 40667363
2025 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. Frontiers in genetics 0 41306914
2024 Novel Variants of CEP152 in a Case of Compound-Heterozygous Inheritance of Epilepsy. Global medical genetics 0 38229970

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