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CEP152

Centrosomal protein of 152 kDa · UniProt O94986

Length
1710 aa
Mass
195.6 kDa
Annotated
2026-04-28
21 papers in source corpus 16 papers cited in narrative 16 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CEP152 is a pericentriolar scaffold protein essential for centriole duplication, centrosome integrity, and proper spindle assembly. It forms a ring-like heterotetrameric complex with CEP63 and CEP57 at the proximal end of centrioles, assembled through hydrophobic-motif-driven liquid-liquid phase separation into a cylindrical architecture, and anchored to procentrioles by NuSAP (PMID:23333316, PMID:33208041, PMID:41616107). CEP152 recruits PLK4 to centrosomes via electrostatic interaction between its negatively charged N-terminal domain and PLK4's cryptic polo-box, cooperating hierarchically with CEP192, and actively stimulates PLK4 kinase autophosphorylation and activation to initiate centriole biogenesis (PMID:21059844, PMID:21059850, PMID:24277814, PMID:40372713). CEP152 is also an APC/C substrate whose ubiquitylation during mitosis releases CEP57 to enable pericentrin interaction and microtubule nucleation for spindle assembly, and loss-of-function mutations in CEP152 cause autosomal recessive primary microcephaly (MCPH4) and Seckel syndrome (PMID:34878135, PMID:20598275, PMID:21131973).

Mechanistic history

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

    Establishing that CEP152 (the vertebrate ortholog of Drosophila Asterless) is essential for centriole duplication and cilia formation answered a fundamental question about whether this pericentriolar protein has a structural versus functional role in centriole biogenesis.

    Evidence Cross-species genetic loss-of-function (Drosophila mecD alleles, zebrafish morpholinos) with rescue experiments and immunolocalization

    PMID:18854586

    Open questions at the time
    • Binding partners mediating CEP152's role in duplication were unknown
    • Mechanism by which CEP152 promotes daughter centriole formation was unresolved
    • Mammalian loss-of-function phenotype not yet characterized
  2. 2010 High

    Two independent studies demonstrated that CEP152 directly recruits PLK4 to centrosomes through its N-terminal domain binding PLK4's cryptic polo-box, resolving how the key centriole duplication kinase is positioned at the centrosome.

    Evidence Reciprocal Co-IP, RNAi depletion with centriole duplication failure, overexpression of N-terminal fragments, in vitro PLK4 kinase assay in human and frog cells

    PMID:21059844 PMID:21059850

    Open questions at the time
    • Whether CEP152-PLK4 interaction is sufficient for PLK4 activation or only for recruitment was unclear
    • Relationship to other PLK4 receptors (e.g., CEP192) was unknown
    • Structural basis of the interaction was not determined
  3. 2010 Medium

    Human genetic studies linked CEP152 mutations to both autosomal recessive primary microcephaly (MCPH4) and Seckel syndrome, establishing CEP152 as essential for normal brain development and genome integrity.

    Evidence Homozygosity mapping, exome sequencing in consanguineous families, localization assays with truncation mutants, and DNA-damage response assays in patient cells

    PMID:20598275 PMID:21131973

    Open questions at the time
    • Precise mechanism linking centrosome defects to microcephaly versus genome instability was not disentangled
    • Animal models recapitulating human disease phenotypes were lacking
    • Whether different CEP152 mutations cause distinct clinical presentations through different molecular mechanisms was unclear
  4. 2013 High

    The discovery that CEP152 and CEP192 cooperate hierarchically and competitively to recruit PLK4 via homologous acidic N-terminal motifs, and that CEP57–CEP63–CEP152 form a ring-like complex at the proximal centriole, defined the spatial and biochemical framework for PLK4 positioning.

    Evidence Competitive binding assays, double-depletion epistasis, selective chemical crosslinking, STED superresolution microscopy, domain mapping

    PMID:23333316 PMID:23641073 PMID:24277814

    Open questions at the time
    • How the ring complex assembles around the centriole was unknown
    • Whether PLK4 interaction with CEP152 is purely for recruitment or also regulates kinase activity was unresolved
    • The stoichiometry and dynamics of the CEP57–CEP63–CEP152 complex were not determined
  5. 2018 Medium

    Demonstration that CEP152 is actively excluded from acentriolar MTOCs during meiosis in a CDK1-dependent manner revealed a regulated, cell-type-specific role for CEP152 removal in MTOC remodeling during oocyte spindle formation.

    Evidence Immunofluorescence and RNAi in mouse oocytes with CDK1 inhibitor treatment

    PMID:28970258

    Open questions at the time
    • Direct CDK1 phosphorylation sites on CEP152 were not identified
    • Relevance to somatic cell mitotic MTOC dynamics was not explored
    • Whether this mechanism operates in human oocytes was not tested
  6. 2020 High

    In vitro reconstitution showed that the CEP63–CEP152 heterotetrameric complex self-assembles into cylindrical structures via liquid-liquid phase separation driven by hydrophobic motifs, providing a physical mechanism for centrosomal scaffold formation.

    Evidence Purified complex reconstitution, FRAP, 1,6-hexanediol treatment, 3D-SIM superresolution, CLEM, hydrophobic-motif mutagenesis

    PMID:33208041

    Open questions at the time
    • How phase separation is regulated in vivo (e.g., by phosphorylation) was not addressed
    • The role of CEP57 in regulating or modulating phase separation was not tested
    • Whether phase separation is required for centriole duplication per se was not established
  7. 2022 High

    The finding that APC/C ubiquitylates CEP152 at the centrosome during mitosis, releasing CEP57 to interact with pericentrin and promote microtubule nucleation, revealed a second major function for CEP152 beyond centriole duplication — as a regulated inhibitor of spindle assembly.

    Evidence Co-IP, ubiquitylation assays, RNAi/KO with spindle phenotype, proximity ligation assay, immunofluorescence

    PMID:34878135

    Open questions at the time
    • Specific ubiquitylation sites on CEP152 and the degron recognized by APC/C were not mapped
    • Whether APC/C-mediated CEP152 degradation is coupled to centriole licensing in the next cycle was unknown
    • The APC/C activator (Cdh1 vs. Cdc20) mediating CEP152 ubiquitylation was not identified
  8. 2023 Medium

    Nanoscale mapping showed that CEP152 adopts a complex, non-ninefold-symmetric distribution during centriole maturation while being anchored in ninefold symmetry by CEP57/CEP63, explaining how a single molecule can serve as a flexible PLK4 receptor that does not rigidly constrain procentriole placement.

    Evidence Expansion microscopy (U-ExM), STORM superresolution, endogenous tagging, depletion experiments

    PMID:37707473

    Open questions at the time
    • Molecular basis of the symmetry-breaking during maturation was not identified
    • Whether CEP152 flexibility directly determines the site of procentriole emergence was not functionally tested
    • Temporal dynamics of the symmetry transition were not resolved
  9. 2025 Medium

    Rapid auxin-inducible degradation of CEP152 demonstrated that CEP152 binding does not merely recruit PLK4 but actively stimulates PLK4 kinase activation and autophosphorylation, potentially through stabilizing PLK4 dimers, establishing CEP152 as an allosteric activator of centriole duplication initiation.

    Evidence Auxin-inducible degron system, kinase activation assays, phospho-PLK4 immunofluorescence, biochemical binding assays

    PMID:40372713

    Open questions at the time
    • Direct demonstration of CEP152-stabilized PLK4 dimers is lacking
    • Structural mechanism of allosteric activation is unknown
    • Relative contributions of CEP152 versus CEP192 to PLK4 activation were not quantified
  10. 2025 Medium

    Identification that PLK4 homodimerization via its CPB is required to maintain CEP152 at centrosomes during S phase revealed a reciprocal dependency: CEP152 recruits PLK4 but PLK4 also stabilizes CEP152 at centrosomes.

    Evidence PLK4 CPB-truncation/cancer variant expression, Co-IP, immunofluorescence, cell viability assays

    PMID:40222413

    Open questions at the time
    • Whether CEP152 stabilization by PLK4 involves direct phosphorylation was not tested
    • Relevance of cancer-associated PLK4 variants to CEP152 loss in tumors was not explored
    • Single-lab observation not yet independently replicated
  11. 2026 Medium

    Discovery that NuSAP directly interacts with CEP57 and is required for the initial recruitment of the CEP57–CEP63–CEP152 torus to procentrioles identified an upstream factor in ring complex assembly, answering how the scaffold is first nucleated on newly forming centrioles.

    Evidence TurboID proximity proteomics, Co-IP, superresolution microscopy, RNAi depletion with centriole phenotype readouts

    PMID:41616107

    Open questions at the time
    • Direct binding interface between NuSAP and CEP57 is not structurally defined
    • Whether NuSAP acts catalytically or stoichiometrically in torus assembly is unknown
    • Single-lab finding not yet independently replicated

Open questions

Synthesis pass · forward-looking unresolved questions
  • A complete structural understanding of the CEP152 ring complex at atomic resolution, the precise mechanism by which CEP152 allosterically activates PLK4, the identity of the APC/C degron on CEP152, and how CEP152 mutations differentially cause microcephaly versus Seckel syndrome remain unresolved.
  • No high-resolution structure of CEP152 or the CEP57–CEP63–CEP152 complex exists
  • The specific CEP152 residues required for PLK4 allosteric activation are unmapped
  • How different patient mutations lead to distinct clinical outcomes is mechanistically unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0098772 molecular function regulator activity 2
Localization
GO:0005815 microtubule organizing center 8 GO:0005856 cytoskeleton 3
Pathway
R-HSA-1640170 Cell Cycle 6 R-HSA-1852241 Organelle biogenesis and maintenance 5
Partners
APC/CCEP192CEP57CEP63NUSAPPCNTPLK4
Complex memberships
CEP57-CEP63-CEP152 torus complex

Evidence

Reading pass · 16 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 and is required for PLK4 recruitment to the centrosome and PLK4-induced centriole overduplication; depletion of CEP152 also causes loss of CPAP from centrosomes, monopolar spindles, and failure of centriole duplication. Co-immunoprecipitation, RNAi knockdown with centriole/spindle phenotype readouts, overexpression of N-terminal domain fragment The Journal of cell biology High 21059844
2010 CEP152 interacts with PLK4 through its N-terminal 217 residues and the cryptic Polo-box of PLK4; depletion of CEP152 prevents centriole duplication, PLK4-induced centriole amplification, and Sas6 localization to the centriole (an early duplication step); CEP152 can be phosphorylated by PLK4 in vitro. Co-immunoprecipitation, in vitro kinase assay, RNAi depletion, overexpression of truncation fragments in human and frog cells The Journal of cell biology High 21059850
2010 CEP152 mutations cause Seckel syndrome; impaired CEP152 function leads to accumulation of genomic defects from replicative stress through enhanced ATM signaling and increased H2AX phosphorylation, identifying CEP152 as a regulator of genomic integrity and DNA-damage response. Homozygosity mapping, exome sequencing, functional cellular assays (H2AX phosphorylation, ATM signaling) Nature genetics Medium 21131973
2010 Mutations in CEP152 cause autosomal recessive primary microcephaly (MCPH4); a truncating mutation prevents CEP152 localization to centrosomes in transfected cells, confirming a centrosomal role in mitosis/cell division underlying microcephaly. Genetic mapping, sequencing, transfection/localization assay with truncation mutant American journal of human genetics Medium 20598275
2008 Cep152 (vertebrate ortholog of Drosophila Asterless/Asl) is essential for cilia formation and daughter centriole formation; it localizes closely to the centriole wall but is not part of the centriole structure, and its loss mildly affects PCM but abolishes centriole duplication. Loss-of-function alleles (mecD in Drosophila), morpholino knockdown in zebrafish, immunolocalization, cross-species rescue experiment Genetics High 18854586
2013 Cep192 and Cep152 cooperate for PLK4 centrosome recruitment: Cep192 recruits Cep152 and PLK4 hierarchically; double depletion completely abolishes PLK4 centriole binding and centriole duplication; the PLK4-binding regions of Cep192 (N-terminal extension) and Cep152 (residues 1–46) are rich in negatively charged residues, suggesting electrostatic interaction with PLK4's positively charged polo-box domain. RNAi double-depletion, Co-immunoprecipitation, truncation/domain mapping, centriole duplication assays Journal of cell science High 23641073
2013 Cep192 and Cep152 competitively interact with PLK4's cryptic polo-box through homologous N-terminal sequences (acidic-α-helix and N/Q-rich motifs), and recruit PLK4 to distinct subcentrosomal regions in a hierarchical, spatiotemporally regulated order; loss of either interaction impairs centriole duplication. Co-immunoprecipitation, competitive binding assays, RNAi, overexpression of N-terminal fragments to delocalize PLK4, cell proliferation assay Proceedings of the National Academy of Sciences of the United States of America High 24277814
2013 Cep57, Cep63, and Cep152 form a ring-like complex at the proximal end of centrioles; Cep152 and Plk4 reside in two separable structures, suggesting Plk4 contacts Cep152 only transiently at the centrosome or in the cytoplasm. Selective chemical crosslinking, superresolution microscopy (STED), protein interaction mapping Current biology : CB High 23333316
2018 In mouse oocytes, Cep152 localizes to acentriolar MTOCs at the germinal vesicle stage and is excluded from MTOCs after germinal vesicle breakdown; this exclusion is regulated by CDK1 activity and is required for MTOC fragmentation during meiotic spindle formation. Immunofluorescence, RNAi depletion in mouse oocytes, CDK1 inhibitor treatment, spindle/MTOC phenotype analysis FASEB journal Medium 28970258
2020 Cep63 and Cep152 form a heterotetrameric complex that self-assembles into a cylindrical architecture around centrioles via liquid-liquid phase separation driven by hydrophobic motifs in each protein; 1,6-hexanediol disrupts their centrosomal localization; purified complex forms cylindrical or hollow-sphere structures. In vitro reconstitution of purified complex, FRAP, 1,6-hexanediol treatment, superresolution microscopy (3D-SIM), CLEM, mutagenesis of hydrophobic motifs Cell cycle (Georgetown, Tex.) High 33208041
2022 The APC/C localizes to centrosomes specifically during mitosis; APC/C recruitment to spindle poles requires Cep152; Cep152 is both an APC/C interaction partner and an APC/C substrate; APC/C-mediated ubiquitylation of Cep152 at the centrosome releases Cep57 from the Cep57-Cep63-Cep152 inhibitory complex, enabling Cep57-pericentrin interaction and microtubule nucleation. Co-immunoprecipitation, ubiquitylation assay, RNAi/KO with spindle-assembly phenotype, proximity ligation, immunofluorescence Journal of cell science High 34878135
2023 At nanoscale resolution, Cep152 develops a complex (non-ninefold-symmetric) distribution during centriole maturation and functions as the major PLK4 receptor; Cep57 and Cep63 anchor Cep152 at the proximal end of the mother centriole in ninefold symmetry; the molecular arrangement of Cep152 creates flexibility for PLK4 and procentriole placement. Expansion microscopy / superresolution microscopy (U-ExM, STORM), endogenous tagging, depletion experiments The Journal of cell biology Medium 37707473
2025 Binding of the CEP152 N-terminal region to PLK4 stimulates PLK4 phosphorylation and kinase activation, potentially stabilizing PLK4 dimer formation to allow autophosphorylation; CEP152 controls the levels and localization of phosphorylated PLK4 at the proximal centriole end. Auxin-inducible degron (AID) rapid degradation of CEP152, kinase activation assays, phospho-PLK4 immunofluorescence, biochemical binding assays Molecular biology of the cell Medium 40372713
2025 PLK4 homodimerization via its CPB is required to maintain CEP152 at centrosomes during S phase; a CPB-truncating PLK4 variant cannot homodimerize, cannot interact with CEP152 or CEP192, reduces CEP152 and pericentrin at centrosomes, and causes unfocused spindles and reduced cell viability. Expression of PLK4 truncation/cancer variant, Co-immunoprecipitation, immunofluorescence, cell viability assay Journal of molecular biology Medium 40222413
2025 CEP152, CEP63, and PCNT form ALMS1-interacting aggregates outside the centriole that act as cartwheel seeds (CSs) for centriole biogenesis; these CSs form concentric rings of CEP152 and CEP63 in interphase from which the cartwheel grows; ALMS1 is required for CS assembly from components and thus for de novo centriole formation. TurboID proximity labeling, Co-IP, superresolution microscopy, ALMS1 depletion and rescue, de novo centriole formation assay bioRxivpreprint Medium 40667363
2026 NuSAP directly interacts with CEP57 and is required for the initial recruitment of the CEP57-CEP63-CEP152 torus complex to the proximal end of procentrioles; NuSAP depletion disrupts centriole tubulin architecture, causes premature centriole disengagement, and disrupts CEP57-CEP63-CEP152 spatial organization. TurboID-based proximity proteomics, Co-immunoprecipitation, superresolution microscopy, RNAi depletion with centriole phenotype readouts Advanced science Medium 41616107

Source papers

Stage 0 corpus · 21 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 230 21059844
2010 Cep152 interacts with Plk4 and is required for centriole duplication. The Journal of cell biology 228 21059850
2013 Human Cep192 and Cep152 cooperate in Plk4 recruitment and centriole duplication. Journal of cell science 194 23641073
2010 CEP152 is a genome maintenance protein disrupted in Seckel syndrome. Nature genetics 179 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 177 24277814
2010 Mutations in centrosomal protein CEP152 in primary microcephaly families linked to MCPH4. American journal of human genetics 147 20598275
2008 Drosophila asterless and vertebrate Cep152 Are orthologs essential for centriole duplication. Genetics 135 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 12 34878135
2023 Centrosomal organization of Cep152 provides flexibility in Plk4 and procentriole positioning. The Journal of cell biology 10 37707473
2022 Expression Analyses of Cep152, a Responsible Gene Product for Autosomal Recessive Primary Microcephaly, during Mouse Brain Development. Developmental neuroscience 4 35259752
2023 Two novel variants in CEP152 caused Seckel syndrome 5 in a Chinese family. Frontiers in genetics 2 36685824
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
2025 Binding of CEP152 to PLK4 stimulates kinase activity to promote centriole assembly. Molecular biology of the cell 1 40372713
2026 NuSAP Safeguards Centriole Integrity to Mediate CEP57-CEP152 Torus Recruitment for Proper Engagement. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 41616107
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