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Showing CDK5RAP2 — CEP215 is a alias.

CDK5RAP2

CDK5 regulatory subunit-associated protein 2 · UniProt Q96SN8

Length
1893 aa
Mass
215.0 kDa
Annotated
2026-06-09
84 papers in source corpus 33 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CDK5RAP2 (CEP215) is a pericentriolar material (PCM) scaffold protein that organizes microtubule nucleation by recruiting and activating the γ-tubulin ring complex (γTuRC) at centrosomes and other microtubule-organizing centers (PMID:17959831, PMID:21135143). It binds γTuRC through a short conserved γ-TuNA/CM1 motif that is required to attach γTuRC to the centrosome and that directly stimulates nucleation by purified γTuRC in vitro; cryo-EM of the reconstituted human complex shows that the CM1 motif binds multiple γTuRC modules (MZT2, GCP2) to drive long-range constriction of the γ-tubulin ring toward the 13-protofilament microtubule geometry, the structural basis of nucleation activation (PMID:21135143, PMID:39321808). Beyond γTuRC, CDK5RAP2 tracks growing microtubule plus-ends through an EB1 interaction and regulates microtubule dynamics, stability, and bundling (PMID:19553473). CDK5RAP2 is held at the centrosome largely through its interdependent interaction with pericentrin, with which it forms a matrix (also containing Cep68) required for centrosome maturation, bipolar spindle formation, and centriole engagement/cohesion that restricts centriole replication (PMID:18042621, PMID:20627074, PMID:25503564, PMID:24466316). It links centrosomes to mitotic spindle poles via conserved CNN1/CNN2 domains and a mitosis-specific N-terminal domain that engages Cep192 and phospho-Aurora A, and binds the minus-end motor HSET/KIFC1 to cluster supernumerary centrosomes into pseudo-bipolar spindles (PMID:20368616, PMID:26987684, PMID:33376154). The protein is delivered to and maintained at the centrosome by dynein-dynactin-mediated transport (PMID:20139723, PMID:23874654), and its centrosomal activity is cell-cycle-regulated by PLK1, both directly and through LRRK1-mediated Ser140 phosphorylation within the γ-tubulin-binding motif that enhances γ-tubulin binding and spindle orientation (PMID:25503564, PMID:26192437, PMID:33170211). In addition to its cytoskeletal roles, CDK5RAP2 acts as a nuclear transcriptional regulator of spindle-checkpoint genes (BUBR1, MAD2) and CENP-A, with loss producing chromosome mis-segregation (PMID:19282672, PMID:33725591). Loss of CDK5RAP2 in mice causes microcephaly through premature neural progenitor cell-cycle exit, apoptosis, and spindle defects, establishing its role in neurogenesis (PMID:20471352, PMID:20460369).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 2007 High

    Established that CDK5RAP2 is a PCM-resident protein that anchors γTuRC to the centrosome, defining its core role in centrosomal microtubule nucleation.

    Evidence Co-IP, RNAi, and microtubule nucleation assays in cultured cells

    PMID:17959831

    Open questions at the time
    • Did not resolve whether binding directly activates nucleation versus only tethering γTuRC
    • Mechanism of the conserved γTuRC-binding sequence not structurally defined
  2. 2007 Medium

    Showed CDK5RAP2 maintains interphase centrosome cohesion through a pericentrin-linked mechanism distinct from rootletin/Cep68 fibers.

    Evidence RNAi, immunofluorescence, and co-IP for pericentrin in cultured cells

    PMID:18042621

    Open questions at the time
    • Molecular nature of the cohesion mechanism left vague
    • Single lab
  3. 2010 High

    Defined the γ-TuNA domain as a direct activator of γTuRC nucleation and mapped its association with NME7, FAM128A/B, and actin, distinguishing activation from γTuRC assembly.

    Evidence In vitro nucleation with purified γTuRC, mutagenesis, and RNAi

    PMID:21135143

    Open questions at the time
    • Structural basis of activation not determined at this stage
    • Role of NME7/FAM128 in activation unresolved
  4. 2010 High

    Identified an EB1-binding motif enabling CDK5RAP2 to track microtubule plus-ends and regulate dynamics, extending its role beyond minus-end nucleation.

    Evidence Co-IP, Ile/Leu-Pro dipeptide mutagenesis, live imaging, and in vitro assembly assays

    PMID:19553473

    Open questions at the time
    • How plus-end and minus-end activities are coordinated in cells unknown
  5. 2010 Medium

    Mapped a CM2-like motif mediating pericentrin/AKAP450 binding that targets CDK5RAP2 to both centrosomes and Golgi, with calmodulin binding dispensable.

    Evidence Mutational analysis, co-IP, and subcellular fractionation

    PMID:20466722

    Open questions at the time
    • Functional role of the Golgi pool not established
    • Single lab
  6. 2010 High

    Defined conserved CNN1/CNN2 domains that recruit PCM for centrosome-spindle pole attachment and link CDK5RAP2 to centriole cohesion and the G2 DNA-damage checkpoint.

    Evidence Domain deletion and gene disruption in DT40 cells with multiple phenotypic readouts

    PMID:20368616

    Open questions at the time
    • Direct PCM components recruited by CNN1 not all identified
    • Mechanistic link to DNA-damage arrest unclear
  7. 2010 High

    Established CDK5RAP2-pericentrin interdependence in neural progenitors and that its loss drives premature differentiation, connecting centrosome function to neurogenesis.

    Evidence Reciprocal RNAi phenocopy, co-IP, and cell-cycle analysis in neural progenitors

    PMID:20471352

    Open questions at the time
    • How spindle/centrosome defects translate to fate decisions not fully resolved
  8. 2010 High

    Demonstrated in vivo that Cdk5rap2 loss causes microcephaly via progenitor cell-cycle exit, apoptosis, and spindle abnormalities, and that it restricts centriole amplification.

    Evidence Mouse mutant/KO models with EM, BrdU labeling, and spindle/cilia analysis

    PMID:20460369 PMID:20627074

    Open questions at the time
    • Relative contributions of cohesion versus nucleation defects to microcephaly unresolved
  9. 2010 Medium

    Showed CDK5RAP2 centrosomal localization depends on dynein-dynactin and that it is in turn required for centrosomal dynein, defining bidirectional transport coupling.

    Evidence RNAi, live imaging, and dynein-dynactin perturbation

    PMID:20139723

    Open questions at the time
    • Direct versus indirect dynein dependency not separated
    • Single lab
  10. 2013 Medium

    Demonstrated dynamic, microtubule-dependent centrosomal turnover of CDK5RAP2 via a dynein light chain 8-binding motif.

    Evidence FRAP, co-IP, and dominant-negative dynein-dynactin disruption

    PMID:23874654

    Open questions at the time
    • Functional consequence of turnover dynamics not established
    • Single lab
  11. 2014 High

    Placed CDK5RAP2 in a PLK1-regulated proteolytic circuit (Cep68/SCF-βTrCP, PCNT cleavage) controlling its removal from PCM to govern centriole disengagement and duplication.

    Evidence Co-IP, mass spectrometry, degradation assays, and phospho-site mutagenesis

    PMID:25503564

    Open questions at the time
    • How peripheral versus core PCM pools are differentially regulated mechanistically unclear
  12. 2014 Medium

    Showed CDK5RAP2-pericentrin interdependence drives centrosome maturation and bipolar spindle formation, with γ-tubulin binding dispensable for maturation itself.

    Evidence Knockdown-rescue with domain mutants and immunofluorescence

    PMID:24466316

    Open questions at the time
    • Separating maturation scaffolding from nucleation function incompletely resolved
    • Single lab
  13. 2015 High

    Identified a PLK1>LRRK1>CDK5RAP2 Ser140 phosphorylation cascade that enhances γ-tubulin binding and regulates spindle orientation, linking mitotic kinase signaling to nucleation.

    Evidence In vitro kinase assay, phospho-site mutagenesis, co-IP, and spindle orientation assays

    PMID:26192437

    Open questions at the time
    • Whether other kinases redundantly target the γ-tubulin-binding motif unknown
  14. 2016 High

    Established direct CDK5RAP2-HSET/KIFC1 binding that clusters supernumerary centrosomes into pseudo-bipolar spindles in cancer cells.

    Evidence Proteomics, co-IP, domain deletion, and patient-derived cell validation

    PMID:26987684

    Open questions at the time
    • Whether this clustering function is druggable in vivo not addressed
  15. 2016 High

    Defined functional redundancy between CDK5RAP2 and ASPM in spindle pole focusing that is independent of HSET localization and γ-tubulin activation.

    Evidence CRISPR KO, auxin-inducible degron, RNAi, and immunofluorescence

    PMID:28883092

    Open questions at the time
    • Molecular basis of the pole-focusing activity unidentified
  16. 2009 Medium

    Revealed an unexpected nuclear transcriptional role for CDK5RAP2 in regulating spindle-checkpoint genes BUBR1 and MAD2.

    Evidence RNAi, ChIP at promoters, and immunoblotting

    PMID:19282672

    Open questions at the time
    • How a centrosomal scaffold acts as a transcriptional regulator unexplained
    • Single lab
  17. 2020 High

    Demonstrated the PCNT-CDK5RAP2 matrix becomes essential for acentriolar spindle assembly via a microtubule- and PLK1-dependent process requiring γ-tubulin recruitment.

    Evidence Centrinone-induced centriole loss, CRISPR KO of PCNT and CDK5RAP2, and live imaging

    PMID:33170211

    Open questions at the time
    • Trigger that switches matrix assembly to essential mode unclear
  18. 2020 Medium

    Showed CEP215 localizes to oocyte acentriolar MTOCs in a pericentrin-dependent, Aurora A-sensitive manner and regulates meiotic spindle pole focusing without affecting γ-tubulin recruitment.

    Evidence siRNA, Aurora A inhibition, and super-resolution microscopy in mouse oocytes

    PMID:31895686

    Open questions at the time
    • Why γ-tubulin recruitment is uncoupled in oocytes unexplained
    • Single lab
  19. 2021 Medium

    Connected CDK5RAP2 to cellular senescence via a GSK3β/β-catenin/WIP1 axis through direct GSK3β binding and inhibitory Ser9 phosphorylation.

    Evidence Co-IP, phospho-immunoblotting, and knockdown-rescue with ectopic WIP1

    PMID:34930892

    Open questions at the time
    • Whether this signaling is centrosome-dependent unknown
    • Single lab
  20. 2021 Medium

    Identified CDK5RAP2 as a positive transcriptional regulator of CENP-A whose loss causes chromosome segregation errors.

    Evidence RNAi, ChIP at the CENP-A promoter, and ectopic CENP-A rescue

    PMID:33725591

    Open questions at the time
    • Mechanism of promoter engagement unresolved
    • Single lab
  21. 2024 High

    Provided the structural mechanism of nucleation activation: CM1 binds multiple γTuRC modules to constrict the γ-tubulin ring toward microtubule geometry.

    Evidence Cryo-EM of reconstituted human γTuRC and single-molecule nucleation assays

    PMID:39321808

    Open questions at the time
    • How constriction is regulated by phosphorylation/partners in cells not shown
  22. 2024 Medium

    Placed CDK5RAP2 downstream of the Arl2 GTPase in centrosomal microtubule growth and cortical neurogenesis.

    Evidence Co-IP, proximity ligation, RNAi, and overexpression rescue in mouse cortex

    PMID:39137170

    Open questions at the time
    • Whether Arl2 regulates CDK5RAP2 localization directly unclear
    • Single lab
  23. 2025 High

    Showed CDK5RAP2 self-assembles into micron-scale, PLK-1-regulated scaffolds that recruit/activate γTuRC and HSET to build microtubule asters, with F75 dispensable for recruitment but essential for activation.

    Evidence In vitro reconstitution, F75 mutagenesis, and aster formation assays (preprint)

    PMID:bio_10.1101_2025.02.20.639226

    Open questions at the time
    • Preprint, single lab
    • Whether scaffold self-assembly occurs identically in cells unverified
  24. 2025 Medium

    Revealed cell-cycle-dependent material-state switching of CEP215 at centrosomes, with pericentrin and coiled-coil domains governing dynamicity and spindle pole assembly.

    Evidence FRAP, light-inducible clustering, and coiled-coil truncation mutagenesis

    PMID:40270183

    Open questions at the time
    • Molecular driver of the solid-to-dynamic transition unclear
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CDK5RAP2's distinct activities—centrosomal scaffolding, γTuRC activation, plus-end tracking, and nuclear transcriptional regulation—are integrated and spatially partitioned within one protein remains unresolved.
  • Mechanism connecting cytoplasmic scaffolding to promoter-level transcriptional control unknown
  • Coordination of multiple binding motifs across the cell cycle undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 3 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3 GO:0140110 transcription regulator activity 2
Localization
GO:0005815 microtubule organizing center 3 GO:0005634 nucleus 2 GO:0005794 Golgi apparatus 1 GO:0005856 cytoskeleton 1
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-1640170 Cell Cycle 3 R-HSA-1852241 Organelle biogenesis and maintenance 3
Partners
AKAP450CEP192CEP68EB1GSK3BHSET/KIFC1NEDD1PCNT
Complex memberships
CEP215-Cep68-PCNT complexPCNT-CDK5RAP2 pericentriolar matrixγ-tubulin ring complex (γTuRC)

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 CDK5RAP2 localizes throughout the pericentriolar material (PCM) in all cell cycle stages and associates with the γ-tubulin ring complex (γTuRC) via a short conserved sequence. This binding is required for γTuRC attachment to the centrosome (but not γTuRC assembly), and perturbing CDK5RAP2 function delocalizes γ-tubulin from centrosomes and inhibits centrosomal microtubule nucleation, leading to disorganized interphase microtubule arrays and anastral mitotic spindles. Co-immunoprecipitation, overexpression, RNAi knockdown, immunofluorescence, microtubule nucleation assays Molecular biology of the cell High 17959831
2010 CDK5RAP2 contains a γ-TuRC-mediated nucleation activator (γ-TuNA) domain that directly stimulates microtubule nucleation by purified γTuRC in vitro. γ-TuNA associates with γTuRC containing NME7, FAM128A/B, and actin in addition to γ-tubulin and GCP2-6. RNAi depletion of CDK5RAP2 impairs both centrosomal and acentrosomal microtubule nucleation without affecting γTuRC assembly. In vitro microtubule nucleation assay with purified γTuRC, co-immunoprecipitation, RNAi, microtubule regrowth assay, active-site/binding-domain mutagenesis The Journal of cell biology High 21135143
2007 CDK5RAP2 (Cep215) is required for centrosome cohesion during interphase. Unlike rootletin/Cep68 which form centriole-associated fibres, Cep215 associates with centrosomes throughout the cell cycle and functionally interacts with pericentrin to influence centrosome cohesion through a mechanism related to cytoskeletal dynamics. RNAi knockdown, immunofluorescence, co-immunoprecipitation, overexpression Journal of cell science Medium 18042621
2010 CDK5RAP2 localizes to the Golgi complex in an ATP- and centrosome-dependent manner and associates with Golgi membranes independently of microtubules. A CM2-like motif in CDK5RAP2 is essential for centrosomal and Golgi localization by mediating binding to pericentrin (required for both centrosomal and Golgi localization) and AKAP450 (required for Golgi localization). Calmodulin binding to this motif is dispensable for centrosomal and Golgi association. Mutational analysis, co-immunoprecipitation, immunofluorescence, subcellular fractionation The Journal of biological chemistry Medium 20466722
2010 CDK5RAP2 interacts with EB1 via a conserved basic and Ser-rich motif containing an Ile/Leu-Pro dipeptide, enabling CDK5RAP2 to track growing microtubule plus-ends. Mutation of the Ile/Leu-Pro dipeptide abolishes EB1 interaction and plus-end attachment. The CDK5RAP2-EB1 complex regulates microtubule dynamics, stability, and bundling; CDK5RAP2 depletion impairs microtubule dynamic behaviors, and the complex stimulates microtubule assembly and bundle formation in vitro. Co-immunoprecipitation, site-directed mutagenesis, live cell imaging, RNAi, in vitro microtubule assembly assay Molecular biology of the cell High 19553473
2010 CDK5RAP2 loss-of-function in mice causes centriole amplification with a preponderance of unpaired single centrioles and daughter-daughter centriole pairs, indicating CDK5RAP2 is required to maintain centriole engagement and cohesion to restrict centriole replication. Early in mitosis, amplified centrosomes assemble multipolar spindles. Excess mother centrioles also template multiple primary cilia. Mouse knockout model (Cdk5rap2 mutant), electron microscopy, immunofluorescence, cilia analysis Developmental cell High 20627074
2010 CDK5RAP2 links centrosomes to mitotic spindle poles via two evolutionarily conserved domains, CNN1 and CNN2, in vertebrate cells. The CNN1 domain is required for recruiting specific PCM components that mediate centrosome-spindle pole attachment, and also enforces centriole cohesion during interphase and promotes efficient DNA damage-induced G2 cell cycle arrest. Domain deletion mutagenesis, gene disruption in DT40 cells, immunofluorescence, DNA damage response assays The Journal of cell biology High 20368616
2010 Cdk5rap2 interacts with pericentrin in neural progenitor cells, and loss of Cdk5rap2 depletes apical progenitors and increases cell-cycle exit leading to premature neuronal differentiation. Depletion of pericentrin phenocopies Cdk5rap2 knockdown and results in decreased Cdk5rap2 recruitment to the centrosome, establishing a functional epistatic relationship. RNAi knockdown in neural progenitors, co-immunoprecipitation, immunofluorescence, cell cycle analysis Neuron High 20471352
2010 Cdk5rap2 mouse mutants exhibit microcephaly resulting from neurogenic defects including premature cell cycle exit and apoptosis of neuronal progenitors, associated with impaired mitotic progression, abnormal spindle pole number, and abnormal mitotic orientation. The an mutation is a genomic inversion causing an in-frame deletion of exon 4. Mouse mutant model (Hertwig's anemia an/an), BrdU/EdU labeling, immunofluorescence, spindle pole analysis Development (Cambridge, England) High 20460369
2010 CEP215 (CDK5RAP2) is involved in dynein-dependent accumulation of pericentriolar matrix proteins for spindle pole formation. Knockdown of CEP215 results in monopolar spindle formation, decreased inter-pole distance, and centrosome detachment from spindle poles. CEP215 is critical for centrosomal localization of dynein throughout the cell cycle, and its own centrosomal localization depends on the dynein-dynactin complex. RNAi knockdown, immunofluorescence, live cell imaging Cell cycle (Georgetown, Tex.) Medium 20139723
2013 CDK5RAP2 displays highly dynamic attachment to centrosomes in a microtubule-dependent manner. CDK5RAP2 associates with the retrograde transporter dynein-dynactin and contains a sequence motif that binds dynein light chain 8. Disruption of dynein-dynactin function reduces centrosomal CDK5RAP2 levels. FRAP (live cell imaging), co-immunoprecipitation, dominant-negative dynein-dynactin disruption PloS one Medium 23874654
2014 CEP215 (CDK5RAP2) forms a complex with Cep68 and PCNT (pericentrin). Cep68 degradation via SCF(βTrCP) (initiated by PLK1 phosphorylation at Ser332) allows CEP215 removal from the peripheral PCM to prevent centriole separation following disengagement, while PCNT cleavage mediates CEP215 removal from the core PCM to inhibit centriole disengagement and duplication. Co-immunoprecipitation, mass spectrometry, protein degradation assays, phospho-site mutagenesis Nature cell biology High 25503564
2014 CEP215 and pericentrin are interdependent for their accumulation at spindle poles during mitosis. The CEP215-pericentrin interaction is required for centrosome maturation and subsequent bipolar spindle formation during mitosis. CEP215 interaction with γ-tubulin is dispensable for centrosome maturation. RNAi knockdown-rescue experiments with domain mutants, immunofluorescence PloS one Medium 24466316
2015 LRRK1, activated by PLK1 phosphorylation at Ser1790, phosphorylates CDK5RAP2 at Ser140 within its γ-tubulin-binding motif. This phosphorylation promotes CDK5RAP2-γ-tubulin interaction and CDK5RAP2-dependent microtubule nucleation from centrosomes, thereby regulating mitotic spindle orientation. In vitro kinase assay, phospho-site mutagenesis, co-immunoprecipitation, immunofluorescence, spindle orientation assay Nature cell biology High 26192437
2016 CEP215 directly binds the minus-end-directed microtubule motor HSET (KIFC1). Targeted deletion of the HSET-binding domain of CEP215 causes centrosome detachment and HSET depletion at centrosomes. The CEP215-HSET complex promotes clustering of extra centrosomes into pseudo-bipolar spindles in cancer cells with centrosome amplification. Proteomic profiling, co-immunoprecipitation, targeted domain deletion in vertebrate cells, immunofluorescence Nature communications High 26987684
2009 CDK5RAP2 is required for spindle checkpoint function. CDK5RAP2 knockdown causes chromosome mis-segregation, fails to maintain the spindle checkpoint, reduces expression of spindle checkpoint proteins BUBR1 and MAD2, and increases chromatin-associated CDC20. CDK5RAP2 resides on BUBR1 and MAD2 promoters and regulates their transcription. RNAi knockdown, chromatin immunoprecipitation (ChIP), flow cytometry, immunoblotting Cell cycle (Georgetown, Tex.) Medium 19282672
2017 ASPM functions redundantly with CDK5RAP2 in spindle pole organization during mitotic metaphase in human cells. Depletion of CDK5RAP2 in ASPM knockout cells causes spindle pole unfocusing and delayed anaphase onset. The pole-focusing function of CDK5RAP2 is independent of its known role to localize HSET or to activate the γ-tubulin complex. CRISPR-based gene knockout, auxin-inducible degron, RNAi, immunofluorescence Journal of cell science High 28883092
2020 The PCNT-CDK5RAP2 pericentriolar matrix becomes essential for mitotic spindle assembly when centrioles are absent. In acentriolar cells, PCNT and CDK5RAP2 form foci via a microtubule- and PLK1-dependent process. Foci formation and spindle assembly require PCNT-CDK5RAP2-dependent matrix assembly and the ability of CDK5RAP2 to recruit γ-tubulin complexes. Centriole inhibition (centrinone), CRISPR KO of PCNT and CDK5RAP2, immunofluorescence, live cell imaging The Journal of cell biology High 33170211
2020 CEP215 (CDK5RAP2) localizes to acentriolar MTOCs (aMTOCs) in mouse oocytes in a pericentrin-dependent manner and participates in regulation of meiotic spindle pole focusing. Aurora Kinase A inhibition causes striking loss of the ring-like aMTOC organization and pronounced CEP215 clustering. Unlike in mitotic cells, CEP215 depletion in oocytes does not reduce γ-tubulin at aMTOCs. siRNA knockdown, Aurora Kinase A inhibition, super-resolution microscopy, immunofluorescence Reproduction (Cambridge, England) Medium 31895686
2021 Loss of CDK5RAP2 causes premature cell senescence through a GSK3β/β-catenin/WIP1 pathway. CDK5RAP2 interacts with GSK3β and causes inhibitory Ser9 phosphorylation of GSK3β. Loss of CDK5RAP2 increases GSK3β activity, reducing nuclear β-catenin and thereby downregulating the NF-κB target gene WIP1, which leads to elevated p53 Ser15 phosphorylation and senescence. Ectopic WIP1 expression reverses the senescent phenotype. RNAi knockdown, co-immunoprecipitation, phospho-immunoblotting, rescue experiments with ectopic expression Cell death & disease Medium 34930892
2021 CDK5RAP2 functions as a positive transcriptional regulator of CENP-A. CDK5RAP2 is present in the nucleus, interacts with the CENP-A promoter, and upregulates CENP-A transcription. Loss of CDK5RAP2 reduces centromeric CENP-A levels and causes lagging chromosomes, micronuclei, and chromatin bridges. Exogenous CENP-A expression partially rescues lagging chromosomes in CDK5RAP2 knockdown cells. RNAi knockdown, chromatin immunoprecipitation (ChIP), ectopic expression rescue, immunofluorescence Biomedicine & pharmacotherapy Medium 33725591
2022 Pathogenic LRRK2 causes centrosomal displacement of CDK5RAP2 via a mechanism requiring Rab protein phosphorylation by LRRK2 and RILPL1. The pathogenic LRRK2-mediated centrosomal cohesion deficits are dependent on both the GTP conformation and phosphorylation status of Rab proteins. CDK5RAP2 displacement by LRRK2 does not involve displacement of proteinaceous linker proteins but specifically requires phospho-Rab/RILPL1 centrosomal association. iPSC-derived cells from patients, transiently transfected cell lines, immunofluorescence, LRRK2 kinase inhibition iScience Medium 35721463
2024 CDK5RAP2's centrosomin motif 1 (CM1) induces partial closure of the γ-TuRC by binding multiple modules containing MZT2, GCP2, and CDK5RAP2, resulting in long-range constriction of the γ-tubulin ring toward the geometry of 13-protofilament microtubules. Additional CDK5RAP2 promotes γ-TuRC decoration and stimulates microtubule-nucleating activities in single-molecule assays. Cryo-EM structure determination, in vitro single-molecule microtubule nucleation assay, reconstituted human γ-TuRC Developmental cell High 39321808
2016 CDK5RAP2 interacts with Hippo signaling pathway components MST1 kinase and the transcriptional regulator TAZ. In patient fibroblasts with CDK5RAP2 mutations, higher levels of TAZ and YAP are observed, but common Hippo target genes are downregulated while BIRC5 (Survivin) is upregulated. Co-immunoprecipitation, patient-derived fibroblasts, immunoblotting Molecular genetics and genomics : MGG Low 28004182
2015 Cep169 is a novel centrosomal protein that directly interacts with CDK5RAP2 through CM1, an evolutionarily conserved domain, and colocalizes with CDK5RAP2 at the PCM and at microtubule plus-ends via EB1. Cep169 regulates microtubule stability; its depletion induces microtubule depolymerization but it is not required for γ-tubulin assembly at centrosomes by CDK5RAP2. Co-immunoprecipitation, RNAi knockdown, immunofluorescence, EB1-binding domain mutagenesis PloS one Medium 26485573
2020 A mitosis-specific centrosome-targeting domain of Cep215 (215N) interacts with Cep192 and phosphorylated Aurora A (pAurA), with Cep192 being essential for targeting 215N to centrosomes and centrosomal localization of 215N and pAurA being mutually dependent. Rescue experiments show Cep215 maintains structural integrity of spindle poles by providing a platform for centrosome maturation molecules, with relatively minor role in γ-tubulin recruitment to mitotic centrosome. Domain deletion analysis, co-immunoprecipitation, immunofluorescence, rescue experiments Journal of cell science Medium 33376154
2024 Arl2 GTPase physically associates with Cdk5rap2 (validated by co-immunoprecipitation and proximity ligation assay). Arl2 knockdown reduces centrosomal microtubule growth and causes delocalization of Cdk5rap2 and γ-tubulin from centrosomes. Cdk5rap2 overexpression rescues neurogenesis defects caused by Arl2 knockdown, placing Cdk5rap2 downstream of Arl2 in cortical development. Co-immunoprecipitation, proximity ligation assay, RNAi knockdown, overexpression rescue, in vivo mouse cortical development assay PLoS biology Medium 39137170
2025 CDK5RAP2 is sufficient to form micron-scale scaffolds around a nanometer-scale nucleator in a PLK-1-regulated manner in vitro. CDK5RAP2 assemblies recruit and activate γTuRCs to generate microtubule asters. F75 in CDK5RAP2 is partially needed for γTuRC recruitment but indispensable for γTuRC activation. CDK5RAP2 scaffolds selectively recruit HSET/KifC1, which enhances α/β-tubulin concentration, microtubule polymerization, and clustering. In vitro reconstitution, mutagenesis (F75), microtubule aster formation assay, PLK1 regulation assay bioRxivpreprint High bio_10.1101_2025.02.20.639226
2025 CEP215 (CDK5RAP2) exhibits a dynamically suppressed, solid-like state in interphase centrosomes that becomes more dynamic in mitosis. Interaction with PCNT is crucial for diffusible molecular dynamicity of CEP215. Truncation of CEP215 coiled-coil domains (CCDs) impairs cluster formation and causes spindle pole assembly and spindle formation defects. FRAP, light-inducible clustering assay, coiled-coil domain truncation mutagenesis, immunofluorescence Journal of cell science Medium 40270183
2024 CDK5RAP2 is required for male germ cell development via maintenance of Sertoli cell microtubule organization and blood-testis barrier (BTB) formation. Complete KO of Cep215 in mice results in arrested male germ cell development around the zygotene stage of meiosis and impaired BTB formation in testes. Conditional/complete knockout mouse model, histological analysis, immunofluorescence FASEB journal Medium 39569992
2020 Cep215 is required for morphological differentiation of astrocytes. Cep215 localizes specifically at glial processes as well as centrosomes in developing astrocytes; its deletion suppresses morphological differentiation without affecting cell proliferation or specification. The microtubule-organizing function of Cep215 is critical for glial process formation. CRISPR KO (P19 cells), RNAi (embryonic hippocampal cultures), immunofluorescence Scientific reports Medium 33046744
2024 In the presence of both CDK5RAP2 and NEDD1, both factors can associate with the 'open' conformation of γ-TuRC simultaneously. NEDD1 does not induce conformational changes in γ-TuRC, while CDK5RAP2 interacts with GCP2 to induce conformational changes that promote microtubule nucleation. Cryo-EM structure of γ-TuRC bound simultaneously to NEDD1 and CDK5RAP2, biochemical pulldown mutants bioRxivpreprint Medium bio_10.1101_2024.11.05.622067
2024 An alternative splice isoform of mouse CDK5RAP2 lacking exon 17 generates a truncated protein without a centrosomal localization signal that localizes diffusely in the cytoplasm. This isoform co-immunoprecipitates with γ-tubulin and MOZART2 and, when overexpressed, induces cytoplasmic microtubule nucleation during microtubule regrowth assays. Co-immunoprecipitation, microtubule regrowth assay, ectopic expression IBRO neuroscience reports Low 36164503

Source papers

Stage 0 corpus · 84 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 A centrosomal mechanism involving CDK5RAP2 and CENPJ controls brain size. Nature genetics 447 15793586
2010 CDK5RAP2 stimulates microtubule nucleation by the gamma-tubulin ring complex. The Journal of cell biology 240 21135143
2007 CDK5RAP2 is a pericentriolar protein that functions in centrosomal attachment of the gamma-tubulin ring complex. Molecular biology of the cell 236 17959831
2010 Cdk5rap2 regulates centrosome function and chromosome segregation in neuronal progenitors. Development (Cambridge, England) 219 20460369
2007 Cep68 and Cep215 (Cdk5rap2) are required for centrosome cohesion. Journal of cell science 176 18042621
2010 Cdk5rap2 interacts with pericentrin to maintain the neural progenitor pool in the developing neocortex. Neuron 147 20471352
2010 CDK5RAP2 regulates centriole engagement and cohesion in mice. Developmental cell 142 20627074
2010 Conserved motif of CDK5RAP2 mediates its localization to centrosomes and the Golgi complex. The Journal of biological chemistry 112 20466722
2011 Cdk5rap2 exposes the centrosomal root of microcephaly syndromes. Trends in cell biology 101 21632253
2010 CDK5RAP2 functions in centrosome to spindle pole attachment and DNA damage response. The Journal of cell biology 100 20368616
2001 Purification and properties of two chitinolytic enzymes of Serratia plymuthica HRO-C48. Archives of microbiology 75 11734885
2016 A CEP215-HSET complex links centrosomes with spindle poles and drives centrosome clustering in cancer. Nature communications 73 26987684
2007 Mg2+ binding and archaeosine modification stabilize the G15 C48 Levitt base pair in tRNAs. RNA (New York, N.Y.) 72 17652139
2014 Degradation of Cep68 and PCNT cleavage mediate Cep215 removal from the PCM to allow centriole separation, disengagement and licensing. Nature cell biology 70 25503564
2014 Importance of the CEP215-pericentrin interaction for centrosome maturation during mitosis. PloS one 67 24466316
2015 Development of a novel adjuvanted nasal vaccine: C48/80 associated with chitosan nanoparticles as a path to enhance mucosal immunity. European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 66 25818119
2006 Molecular evolution of the brain size regulator genes CDK5RAP2 and CENPJ. Gene 64 16631324
2015 PLK1-dependent activation of LRRK1 regulates spindle orientation by phosphorylating CDK5RAP2. Nature cell biology 59 26192437
2009 Interaction of CDK5RAP2 with EB1 to track growing microtubule tips and to regulate microtubule dynamics. Molecular biology of the cell 59 19553473
2015 Mutations in CDK5RAP2 cause Seckel syndrome. Molecular genetics & genomic medicine 55 26436113
2006 Transient response to imatinib in a chronic eosinophilic leukemia associated with ins(9;4)(q33;q12q25) and a CDK5RAP2-PDGFRA fusion gene. Genes, chromosomes & cancer 54 16845659
2009 CDK5RAP2 is required for spindle checkpoint function. Cell cycle (Georgetown, Tex.) 40 19282672
2010 CEP215 is involved in the dynein-dependent accumulation of pericentriolar matrix proteins for spindle pole formation. Cell cycle (Georgetown, Tex.) 39 20139723
2020 Centriole-independent mitotic spindle assembly relies on the PCNT-CDK5RAP2 pericentriolar matrix. The Journal of cell biology 37 33170211
2012 A novel nonsense CDK5RAP2 mutation in a Somali child with primary microcephaly and sensorineural hearing loss. American journal of medical genetics. Part A 36 22887808
1979 12alpha-Hydroxysteroid dehydrogenase from Clostridium group P strain C48-50 ATCC No. 29733: partial purification and characterization. Journal of lipid research 35 438663
2020 An update of pathogenic variants in ASPM, WDR62, CDK5RAP2, STIL, CENPJ, and CEP135 underlying autosomal recessive primary microcephaly in 32 consanguineous families from Pakistan. Molecular genetics & genomic medicine 32 32677750
2007 Previously described sequence variant in CDK5RAP2 gene in a Pakistani family with autosomal recessive primary microcephaly. BMC medical genetics 32 17764569
2012 CDK5RAP2 expression during murine and human brain development correlates with pathology in primary autosomal recessive microcephaly. Cerebral cortex (New York, N.Y. : 1991) 30 22806269
2017 Human microcephaly ASPM protein is a spindle pole-focusing factor that functions redundantly with CDK5RAP2. Journal of cell science 28 28883092
2013 Clinical and cellular features in patients with primary autosomal recessive microcephaly and a novel CDK5RAP2 mutation. Orphanet journal of rare diseases 28 23587236
2013 The first case of CDK5RAP2-related primary microcephaly in a non-consanguineous patient identified by next generation sequencing. Brain & development 28 23726037
2011 What's the hype about CDK5RAP2? Cellular and molecular life sciences : CMLS 28 21327915
2011 Intranasal immunization with recombinant HA and mast cell activator C48/80 elicits protective immunity against 2009 pandemic H1N1 influenza in mice. PloS one 25 21625486
2020 CDK5RAP2 primary microcephaly is associated with hypothalamic, retinal and cochlear developmental defects. Journal of medical genetics 23 32015000
2015 Loss of γ-tubulin, GCP-WD/NEDD1 and CDK5RAP2 from the Centrosome of Neurons in Developing Mouse Cerebral and Cerebellar Cortex. Acta histochemica et cytochemica 23 26633906
2013 Dynamic recruitment of CDK5RAP2 to centrosomes requires its association with dynein. PloS one 23 23874654
2024 Partial closure of the γ-tubulin ring complex by CDK5RAP2 activates microtubule nucleation. Developmental cell 22 39321808
2015 Exome sequencing identifies recessive CDK5RAP2 variants in patients with isolated agenesis of corpus callosum. European journal of human genetics : EJHG 22 26197979
2016 CDK5RAP2 interaction with components of the Hippo signaling pathway may play a role in primary microcephaly. Molecular genetics and genomics : MGG 21 28004182
2015 Cep169, a Novel Microtubule Plus-End-Tracking Centrosomal Protein, Binds to CDK5RAP2 and Regulates Microtubule Stability. PloS one 20 26485573
2017 CDK5RAP2 Is Required to Maintain the Germ Cell Pool during Embryonic Development. Stem cell reports 19 28162995
2022 Pathogenic LRRK2 regulates centrosome cohesion via Rab10/RILPL1-mediated CDK5RAP2 displacement. iScience 18 35721463
2020 CEP215 and AURKA regulate spindle pole focusing and aMTOC organization in mouse oocytes. Reproduction (Cambridge, England) 18 31895686
2018 CDK5RAP2 gene and tau pathophysiology in late-onset sporadic Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association 16 29360470
2018 CDK5RAP2 Is an Essential Scaffolding Protein of the Corona of the Dictyostelium Centrosome. Cells 16 29690637
2015 Loss of CDK5RAP2 affects neural but not non-neural mESC differentiation into cardiomyocytes. Cell cycle (Georgetown, Tex.) 15 25942099
2023 CDK5RAP2 is a Wnt target gene and promotes stemness and progression of oral squamous cell carcinoma. Cell death & disease 14 36774351
2024 MORC2 regulates RBM39-mediated CDK5RAP2 alternative splicing to promote EMT and metastasis in colon cancer. Cell death & disease 13 39048555
2017 A new association between CDK5RAP2 microcephaly and congenital cataracts. Annals of human genetics 13 29271474
2024 Inhibitory effect of phellodendrine on C48/80-induced allergic reaction in vitro and in vivo. International immunopharmacology 12 38744172
2017 A novel mutation in CDK5RAP2 gene causes primary microcephaly with speech impairment and sparse eyebrows in a consanguineous Pakistani family. European journal of medical genetics 12 28778786
2022 Whole exome sequencing identifies a novel mutation in ASPM and ultra-rare mutation in CDK5RAP2 causing Primary microcephaly in consanguineous Pakistani families. Pakistan journal of medical sciences 11 35035405
2013 Intranasal immunization of mice with inactivated virus and mast cell activator C48/80 elicits protective immunity against influenza H1 but not H5. Immunological investigations 10 24295504
2021 CDK5RAP2 loss-of-function causes premature cell senescence via the GSK3β/β-catenin-WIP1 pathway. Cell death & disease 9 34930892
2023 A novel missense variant in CDK5RAP2 associated with non-obstructive azoospermia. Taiwanese journal of obstetrics & gynecology 7 38008501
2021 Centromeric chromatin integrity is compromised by loss of Cdk5rap2, a transcriptional activator of CENP-A. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 7 33725591
2019 Congenital microcephaly-linked CDK5RAP2 affects eye development. Annals of human genetics 7 31355417
2001 Dermal fibroblast morphology is affected by stretching and not by C48/80. Connective tissue research 7 11913768
2021 A Possible Association Between Zika Virus Infection and CDK5RAP2 Mutation. Frontiers in genetics 6 33815457
2021 Further insights into the spectrum phenotype of TRAPPC9 and CDK5RAP2 genes, segregating independently in a large Tunisian family with intellectual disability and microcephaly. European journal of medical genetics 6 34737153
2020 A novel mitosis-specific Cep215 domain interacts with Cep192 and phosphorylated Aurora A for organization of spindle poles. Journal of cell science 6 33376154
2021 Triple deletion of TP53, PCNT, and CEP215 promotes centriole amplification in the M phase. Cell cycle (Georgetown, Tex.) 5 34233584
2021 Study on degranulation of mast cells under C48/80 treatment by electroporation-assisted and ultrasound-assisted surface-enhanced Raman spectrascopy. Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy 5 34536894
2015 Novel Alternative Splice Variants of Mouse Cdk5rap2. PloS one 5 26322982
2015 Species-Specific Expression of Full-Length and Alternatively Spliced Variant Forms of CDK5RAP2. PloS one 5 26550838
2023 Hominoid SVA-lncRNA AK057321 targets human-specific SVA retrotransposons in SCN8A and CDK5RAP2 to initiate neuronal maturation. Communications biology 4 36997626
2023 Inhibitory effect of daphnetin on the C48/80-induced pseudo-allergic reaction. International immunopharmacology 4 37690236
2025 A Rare Cause of Primary Microcephaly: 4 New Variants in CDK5RAP2 Gene and Review of the Literature. American journal of medical genetics. Part A 3 40243280
2025 Sea buckthorn leaves and gallic acid inhibit C48/80-induced pseudo-allergic reaction via the PLC/IP3 signaling pathway both in vitro and in vivo. International immunopharmacology 2 40163943
2025 Enhancement of CEP215 dynamics for spindle pole assembly during mitosis. Journal of cell science 2 40270183
2024 Arl2 GTPase associates with the centrosomal protein Cdk5rap2 to regulate cortical development via microtubule organization. PLoS biology 2 39137170
2024 Roles of Cep215/Cdk5rap2 in establishing testicular architecture for mouse male germ cell development. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2 39569992
2022 An alternative splice isoform of mouse CDK5RAP2 induced cytoplasmic microtubule nucleation. IBRO neuroscience reports 2 36164503
2020 Cep215 is essential for morphological differentiation of astrocytes. Scientific reports 2 33046744
1981 On the production of 12 alpha-hydroxysteroid dehydrogenase from Clostridium group P, strain C48-50 ATCC 29733. Experientia 2 6941897
2018 The regulatory subunit phr2AB of Dictyostelium discoideum phosphatase PP2A interacts with the centrosomal protein CEP161, a CDK5RAP2 ortholog. Genes to cells : devoted to molecular & cellular mechanisms 1 30133996
2013 [Construction and characterization of ompH gene knockout mutant of avian Pasteurella multocida C48-3]. Wei sheng wu xue bao = Acta microbiologica Sinica 1 23614242
2009 A proof of concept study: human C48-placenta immunoregulatory factor is an effective, single therapeutic agent enabling allogeneic, nonmanipulated murine bone marrow transplantation. Experimental hematology 1 19539693
2026 EGR1 regulates degranulation and mediator release in C48/80-induced pseudo-allergic reactions. Immunologic research 0 42217066
2025 Tomatidine Attenuates C48/80-induced Inflammatory Responses in HMC-1 Cells and is Associated with Modulation of the JNK/AP-1/ NF-κB/Caspase-1 Pathway. Current topics in medicinal chemistry 0 40444630
2025 Identification of CDK5RAP2 as a causative gene of focal epilepsy without microcephaly. Seizure 0 40848503
2025 Expanding the Clinical and Molecular Spectrum of Primary Autosomal Recessive Microcephaly: Novel CDK5RAP2 Gene Variants and Functional Insights on the Intronic Variants. Genes 0 41153337
2025 STARD9 and CDK5RAP2-Novel Candidate Genes for 46,XY Complete Gonadal Dysgenesis. International journal of molecular sciences 0 41373726

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