Affinage

CEP170

Centrosomal protein of 170 kDa · UniProt Q5SW79

Length
1584 aa
Mass
175.3 kDa
Annotated
2026-06-09
15 papers in source corpus 10 papers cited in narrative 10 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/7 claims corpus-supported (86%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CEP170 is a forkhead-associated (FHA) domain centrosomal protein that couples microtubule organization to centriole and ciliary biology across mitosis, cilium dynamics, and cortical development (PMID:15616186). It localizes to the subdistal appendages of the mature mother centriole during interphase and to spindle microtubules during mitosis, where it acts as both a Plk1 substrate and a direct microtubule-binding factor (PMID:15616186, PMID:23087211). Its centrosomal and microtubule targeting depend on its C-terminus, through interactions with CCDC120 and on CCDC61-controlled positioning that enables a CEP170-TBK1 complex required for microtubule stability (PMID:30354798, PMID:41888776). CEP170 organizes mitotic microtubules in part by providing the kinesin-13 depolymerase Kif2b a second microtubule-binding site to target it to the spindle, and by supporting proper spindle orientation, astral microtubule stability, and cortical dynein/dynactin localization (PMID:23087211, PMID:39708485). At the primary cilium, CEP170 is recruited to the basal body by WDR62 to bring KIF2A there and drive cilium disassembly, and it associates with the dynein-2 holoenzyme to support intraflagellar transport and hedgehog signalling (PMID:31197141, PMID:31533924, PMID:38533689). Through these activities CEP170 is required for neural progenitor proliferation and neuronal migration during cortical development, with C-terminal truncations producing migration, laminar fate, and dendritic defects (PMID:41888776). CEP170 abundance is post-transcriptionally elevated by NAT10-mediated mRNA acetylation and METTL3-mediated m6A modification, linking its levels to proliferation and chromosomal instability in cancer (PMID:35967285, PMID:39708485).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2004 High

    Established CEP170 as a Plk1 substrate and defined its dual interphase/mitotic localization, framing it as a centrosome-associated regulator of microtubule organization.

    Evidence Y2H, co-IP, in vitro kinase assay, immunoelectron microscopy, and siRNA in cultured cells

    PMID:15616186

    Open questions at the time
    • Functional consequence of Plk1 phosphorylation on CEP170 activity not defined
    • Molecular basis of subdistal appendage targeting not resolved
  2. 2012 High

    Showed CEP170 binds microtubules directly and selectively recruits the depolymerase Kif2b to the spindle, giving it a concrete mechanistic role in spindle microtubule dynamics.

    Evidence In vitro microtubule-binding assay, reciprocal Co-IP and interaction mapping, immunofluorescence

    PMID:23087211

    Open questions at the time
    • Specificity for Kif2b over Kif2a/MCAK structurally unexplained
    • Quantitative contribution to spindle depolymerization not measured
  3. 2015 Medium

    Revealed CEP170 can be hijacked by a bacterial effector, showing its microtubule-organizing function is portable to ectopic sites.

    Evidence Chlamydia IPAM identification, interaction/localization assays, CEP170 siRNA, infectivity assays

    PMID:26220855

    Open questions at the time
    • Direct vs indirect CEP170-IPAM interaction not resolved
    • Mechanism by which CEP170 stimulates inclusion-associated MT assembly unknown
  4. 2018 Medium

    Connected CEP170 centrosomal positioning to a TBK1-dependent microtubule stability function via CCDC61.

    Evidence Ccdc61 siRNA, CEP170 immunofluorescence, CEP170-TBK1 co-IP, MT tip-tracking

    PMID:30354798

    Open questions at the time
    • Whether TBK1 kinase activity acts on CEP170 not established
    • Direct vs CCDC61-bridged CEP170-TBK1 contact not distinguished
  5. 2019 High

    Placed CEP170 in a WDR62→CEP170→KIF2A axis driving cilium disassembly and in WDR62-dependent spermatocyte spindle assembly, linking it to both ciliary and meiotic microtubule control.

    Evidence WDR62 KO mice, cerebral organoids and spermatocytes, Co-IP, KIF2A rescue, cilium/spindle imaging

    PMID:31197141 PMID:31533924

    Open questions at the time
    • How WDR62 stabilizes CEP170 protein levels not defined
    • Timing of CEP170-KIF2A handoff during cell cycle unresolved
  6. 2022 Medium

    Identified CEP170 mRNA as a NAT10 acetylation target, establishing post-transcriptional control of CEP170 abundance as a driver of proliferation and chromosomal instability.

    Evidence acRIP-seq, Ribo-seq, RIP-PCR, knockdown/overexpression rescue, mouse myeloma model

    PMID:35967285

    Open questions at the time
    • Which CEP170 mitotic activity mediates the instability phenotype not pinned down
    • ac4C site(s) on CEP170 mRNA not mapped
  7. 2024 Medium

    Defined a ciliary retrograde-transport role for CEP170 through association with the dynein-2 holoenzyme and support of IFT and hedgehog signalling.

    Evidence Interaction proteomics/Co-IP, CEP170 loss-of-function, IFT assays, Hh reporter, dynein-2 stability analysis

    PMID:38533689

    Open questions at the time
    • Whether CEP170 acts as an assembly factor vs stabilizer of dynein-2 unresolved
    • Direct dynein-2 subunit contact not mapped
  8. 2024 Medium

    Showed METTL3 m6A modification upregulates CEP170, which is required for spindle orientation, astral MT stability, and cortical dynein/dynactin localization, with ASPM as a downstream target.

    Evidence m6A-seq, RNA-seq, MeRIP, synchronization, IF, Co-IP, CEP170 siRNA in esophageal cancer cells

    PMID:39708485

    Open questions at the time
    • Mechanism linking CEP170 to ASPM transcription unclear
    • Direct vs indirect control of cortical dynein/dynactin not separated
  9. 2026 Medium

    Mapped CEP170 centrosomal/MT targeting to a CCDC120-dependent C-terminus and established its requirement for neural progenitor proliferation and neuronal migration in vivo.

    Evidence CRISPR KO cells, in utero electroporation shRNA, Co-IP, MT regrowth assays, flow cytometry, mouse cortex imaging

    PMID:41888776

    Open questions at the time
    • Relative contribution of CCDC120 vs CCDC61 to centrosomal targeting not reconciled
    • Causal link between specific MT defect and migration phenotype not isolated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CEP170's distinct microtubule activities (spindle depolymerase recruitment, cilium disassembly, dynein-2-dependent IFT) are spatially and temporally coordinated by upstream regulators remains unresolved.
  • No structural model of CEP170 domain architecture or its multiple binding interfaces
  • Integration of Plk1 phosphorylation, CCDC61/CCDC120 targeting, and WDR62 recruitment not unified
  • No timeline-described human Mendelian disease link despite cortical and meiotic phenotypes

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 3 GO:0060090 molecular adaptor activity 3
Localization
GO:0005815 microtubule organizing center 3 GO:0005856 cytoskeleton 2 GO:0005929 cilium 2
Pathway
R-HSA-1640170 Cell Cycle 3 R-HSA-1266738 Developmental Biology 2 R-HSA-1852241 Organelle biogenesis and maintenance 2 R-HSA-162582 Signal Transduction 1
Partners
CCDC120CCDC61KIF2AKIF2BPLK1TBK1WDR62

Evidence

Reading pass · 10 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 CEP170 (Cep170) is a forkhead-associated (FHA) domain protein that interacts with Polo-like kinase 1 (Plk1) in vivo and can be phosphorylated by Plk1 in vitro, identifying it as a physiological substrate of Plk1. Cep170 localizes to subdistal appendages of the mature mother centriole during interphase and to spindle microtubules during mitosis. siRNA-mediated depletion and overexpression both impair microtubule organization and cell morphology. Yeast two-hybrid screen, co-immunoprecipitation, in vitro kinase assay, siRNA depletion, immunoelectron microscopy, immunofluorescence Molecular biology of the cell High 15616186
2012 CEP170 binds directly to microtubules in vitro and specifically associates with the kinesin-13 depolymerase Kif2b (but not Kif2a or Kif2c/MCAK) via the C-terminus of Kif2b, providing Kif2b with a second microtubule-binding site to target it to the mitotic spindle. Co-immunoprecipitation, in vitro microtubule-binding assay, protein-protein interaction mapping, immunofluorescence localization Molecular biology of the cell High 23087211
2015 The Chlamydia trachomatis inclusion-localized effector IPAM recruits CEP170 to the inclusion surface and stimulates its microtubule-organizing functions. CEP170 is essential for chlamydial control of host microtubule assembly, inclusion morphogenesis, and bacterial infectivity. Identification of IPAM by localization screen, co-immunoprecipitation/interaction assay, siRNA depletion of CEP170, immunofluorescence of microtubule organization, bacterial infectivity assay Journal of cell science Medium 26220855
2018 Ccdc61 controls the centrosomal localization of CEP170 and is required for the interaction between CEP170 and TANK-binding kinase 1 (TBK1), an interaction required for microtubule stability. Loss of Ccdc61 disrupts spindle symmetry and microtubule organization, in part through mislocalization of CEP170. siRNA depletion of Ccdc61, immunofluorescence of CEP170 localization, co-immunoprecipitation of CEP170-TBK1 complex, microtubule tip-tracking assays Molecular biology of the cell Medium 30354798
2019 WDR62 interacts with CEP170 and promotes CEP170 localization to the basal body of the primary cilium, where CEP170 recruits the microtubule-depolymerizing factor KIF2A to drive cilium disassembly. WDR62 depletion reduces KIF2A's basal body localization, retards cilium disassembly, and causes delayed cell cycle progression in neural progenitor cells; enhanced KIF2A expression partially rescues these deficits. Co-immunoprecipitation, WDR62 knockout mice and cerebral organoids, immunofluorescence of CEP170 and KIF2A localization, cilium length measurement, genetic rescue with KIF2A overexpression Nature communications High 31197141 31533924
2019 WDR62 interacts with CEP170 in spermatocytes; deletion of Wdr62 causes downregulation of CEP170 protein, leading to aberrant spindle assembly and metaphase I arrest in spermatocytes. Co-immunoprecipitation, Wdr62 knockout mice, immunofluorescence of CEP170 protein levels and spindle morphology Development (Cambridge, England) Medium 31533924
2022 NAT10 acetylates CEP170 mRNA (m6A-like ac4C modification) to enhance its translation efficiency, thereby increasing CEP170 protein levels and promoting cell proliferation and chromosomal instability in multiple myeloma cells. Interference with CEP170 attenuates the proliferative effect of NAT10 overexpression. acRIP-seq, ribosome profiling (Ribo-seq), RIP-PCR, siRNA knockdown, overexpression, in vivo mouse model (5TMM3VT) Acta pharmaceutica Sinica. B Medium 35967285
2024 CEP170 interacts with dynein-2 holoenzyme complex components in mammalian cells. Loss of CEP170 perturbs intraflagellar transport (IFT), impairs hedgehog signalling, and reduces stability of the dynein-2 holoenzyme complex, indicating a role for CEP170 in dynein-2 assembly and ciliary retrograde transport. Co-immunoprecipitation/interaction proteomics, CEP170 loss-of-function, IFT assays, hedgehog signalling reporter assay, dynein-2 complex stability analysis Journal of cell science Medium 38533689
2024 METTL3-mediated m6A modification of CEP170 mRNA upregulates CEP170 expression in esophageal cancer. CEP170 is required for proper mitotic spindle orientation and astral microtubule stability; CEP170 knockdown causes spindle misorientation and impairs dynein/dynactin motor complex localization at the cell cortex. ASPM was identified as a downstream transcriptional target of CEP170. m6A-seq, RNA-seq, cell cycle synchronization, immunoblotting, immunofluorescence, co-immunoprecipitation, methylated RNA immunoprecipitation, CEP170 siRNA knockdown International immunopharmacology Medium 39708485
2026 CEP170 C-terminal truncations disrupt its centrosomal and microtubule localization via impaired interaction with CCDC120. Loss of CEP170 impairs microtubule regrowth and organization. In embryonic mouse cortex, Cep170 knockdown causes neuronal migration deficits, altered laminar fate, abnormal dendritic morphology, and impaired neural progenitor proliferation. CRISPR/Cas9 KO cells, in utero electroporation of shRNA, co-immunoprecipitation, microtubule regrowth assays, immunofluorescence, flow cytometry, subcellular fractionation/localization Journal of biomedical science Medium 41888776

Source papers

Stage 0 corpus · 15 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 The forkhead-associated domain protein Cep170 interacts with Polo-like kinase 1 and serves as a marker for mature centrioles. Molecular biology of the cell 198 15616186
1997 Expression and clustered distribution of an inwardly rectifying potassium channel, KAB-2/Kir4.1, on mammalian retinal Müller cell membrane: their regulation by insulin and laminin signals. The Journal of neuroscience : the official journal of the Society for Neuroscience 170 9315894
2019 Modeling microcephaly with cerebral organoids reveals a WDR62-CEP170-KIF2A pathway promoting cilium disassembly in neural progenitors. Nature communications 161 31197141
1997 An ATP-dependent inwardly rectifying potassium channel, KAB-2 (Kir4. 1), in cochlear stria vascularis of inner ear: its specific subcellular localization and correlation with the formation of endocochlear potential. The Journal of neuroscience : the official journal of the Society for Neuroscience 129 9169531
2022 NAT10 promotes cell proliferation by acetylating CEP170 mRNA to enhance translation efficiency in multiple myeloma. Acta pharmaceutica Sinica. B 90 35967285
2012 The microtubule-binding protein Cep170 promotes the targeting of the kinesin-13 depolymerase Kif2b to the mitotic spindle. Molecular biology of the cell 47 23087211
2015 A Chlamydia effector recruits CEP170 to reprogram host microtubule organization. Journal of cell science 40 26220855
1998 Inwardly rectifying K+ channel in retinal Müller cells: comparison with the KAB-2/Kir4.1 channel expressed in HEK293T cells. The Japanese journal of physiology 25 9538292
2019 WDR62 is involved in spindle assembly by interacting with CEP170 in spermatogenesis. Development (Cambridge, England) 22 31533924
2018 Ccdc61 controls centrosomal localization of Cep170 and is required for spindle assembly and symmetry. Molecular biology of the cell 21 30354798
2024 Roles for CEP170 in cilia function and dynein-2 assembly. Journal of cell science 10 38533689
2024 METTL3-mediated CEP170 m6A modifications in spindle orientation and esophageal cancer cell proliferation. International immunopharmacology 4 39708485
2026 CEP170 as a novel molecular link between centrosomal function and cerebral cortical development. Journal of biomedical science 0 41888776
2026 Centromere protein CEP170 is dispensable for mouse spermatogenesis and male fertility. Theriogenology 0 41905261
2025 Current status of KAB in health education for Chinese college students and SEM validation exploration. Frontiers in public health 0 41080875

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