CEP170

CEP170 is a centrosomal scaffold protein that organizes microtubule networks from the mother centriole subdistal appendages, the mitotic spindle, and the ciliary basal body. It directly binds microtubules and recruits kinesin-13 family depolymerases—Kif2b to the mitotic spindle and KIF2A to the basal body via WDR62—thereby controlling spindle integrity, cilium disassembly, and cell cycle progression (PMID:23087211, PMID:31197141). CEP170 also stabilizes the dynein-2 holoenzyme to support intraflagellar transport and hedgehog signaling in primary cilia, and promotes spindle orientation by anchoring the dynein/dynactin complex at the cell cortex (PMID:38533689, PMID:39708485). In the developing cortex, CEP170 is required for neural progenitor proliferation, neuronal migration, and proper laminar organization, with its centrosomal targeting and microtubule association dependent on C-terminal interactions with CCDC120 (PMID:41888776).

1. 2003 Medium

   Identification of CEP170 as a bona fide centrosomal component established the starting point for functional characterization of this previously uncharacterized protein.

   Evidence Mass spectrometry-based protein correlation profiling of purified human centrosome fractions with in vivo localization validation

   PMID:14654843

   Open questions at the time

   • No functional information; identity as centrosomal protein rested on co-fractionation and localization only
2. 2004 High

   Characterization of CEP170 as an FHA-domain protein and Plk1 substrate localized to subdistal appendages revealed it as a cell-cycle-regulated centrosomal scaffold whose perturbation disrupts microtubule organization.

   Evidence Yeast two-hybrid, co-immunoprecipitation, in vitro kinase assay, siRNA knockdown, immunoelectron microscopy

   PMID:15616186

   Open questions at the time

   • Mechanism by which CEP170 organizes microtubules was unknown
   • Functional significance of Plk1 phosphorylation on CEP170 activity not resolved
3. 2012 High

   Discovery that CEP170 directly binds microtubules and selectively recruits the kinesin-13 depolymerase Kif2b to the spindle established its mechanistic role as a specificity factor for microtubule-depolymerizing motors, while super-resolution imaging resolved its ring-like architecture at subdistal appendages.

   Evidence In vitro microtubule-binding assay, reciprocal co-IP, siRNA knockdown, 3D-SIM super-resolution microscopy

   PMID:23087211 PMID:23213374

   Open questions at the time

   • Whether CEP170 recruits other kinesin family members in different cellular contexts was untested
   • Structural basis of the CEP170–Kif2b interaction was unresolved
4. 2015 Medium

   Demonstration that the Chlamydia effector IPAM redirects CEP170 to the bacterial inclusion to reorganize host microtubules showed that CEP170 can nucleate microtubule-organizing activity from non-centrosomal platforms.

   Evidence siRNA knockdown, ectopic bacterial effector expression, infectivity assays, co-localization studies

   PMID:26220855

   Open questions at the time

   • Molecular details of IPAM–CEP170 binding interface unknown
   • Whether other pathogens exploit CEP170 was not examined
5. 2018 Medium

   Placement of CEP170 downstream of Ccdc61 and identification of its interaction with TBK1 as required for microtubule stability defined an upstream regulatory hierarchy controlling CEP170 centrosomal localization during mitosis.

   Evidence siRNA knockdown, co-immunoprecipitation, immunofluorescence, microtubule tip-tracking

   PMID:30354798

   Open questions at the time

   • Direct phosphorylation of CEP170 by TBK1 not demonstrated
   • Independence of Ccdc61 and Plk1 regulatory inputs not established
6. 2019 High

   The WDR62–CEP170–KIF2A axis was identified as a cilium disassembly pathway at the basal body, linking CEP170 to primary cilia dynamics, neural progenitor cell cycle control, and microcephaly pathogenesis.

   Evidence Reciprocal co-IP, Wdr62 mouse knockout and cerebral organoid models, cilium length measurements, rescue with KIF2A overexpression; confirmed in spermatocytes by conditional knockout

   PMID:31197141 PMID:31533924

   Open questions at the time

   • Whether CEP170 functions in cilia independently of WDR62 was unclear
   • Structural basis of CEP170 basal body targeting not defined
7. 2022 Medium

   Identification of CEP170 mRNA as a target of NAT10-mediated ac4C acetylation that enhances its translation connected epitranscriptomic regulation to centrosomal protein dosage and chromosomal instability in multiple myeloma.

   Evidence acRIP-seq, Ribo-seq, RIP-PCR, siRNA epistasis, proliferation assays

   PMID:35967285

   Open questions at the time

   • Whether ac4C modification of CEP170 mRNA occurs in non-malignant cells was not tested
   • Relative contributions of transcriptional vs. epitranscriptomic control of CEP170 levels unknown
8. 2024 Medium

   CEP170 was shown to interact with the dynein-2 complex and support its holoenzyme stability, directly linking CEP170 to intraflagellar transport and hedgehog signaling and extending its ciliary role beyond disassembly to active ciliary trafficking.

   Evidence Co-IP/mass spectrometry, siRNA knockdown, IFT assays, hedgehog signaling reporter assays

   PMID:38533689

   Open questions at the time

   • Whether CEP170 acts as a dynein-2 assembly factor or a stability chaperone is unresolved
   • In vivo ciliopathy phenotypes from CEP170 loss not yet reported
9. 2024 Medium

   METTL3-mediated m6A modification was shown to upregulate CEP170, whose loss causes spindle misorientation and cortical dynein/dynactin mislocalization, revealing CEP170 as a determinant of oriented cell division.

   Evidence m6A-seq, RNA-seq, cell cycle synchronization, co-immunoprecipitation, siRNA knockdown in esophageal cancer cells

   PMID:39708485

   Open questions at the time

   • Mechanism by which CEP170 anchors dynein/dynactin at the cortex is not defined
   • ASPM as a transcriptional target of CEP170 lacks a clear mechanistic pathway
10. 2026 Medium

    In vivo cortical neurodevelopmental studies established that CEP170 is essential for neural progenitor proliferation, neuronal migration, and laminar organization, with its C-terminal domain mediating centrosomal targeting through CCDC120 interaction.

    Evidence In utero electroporation shRNA knockdown, CRISPR/Cas9 knockout, co-IP, microtubule regrowth assay, scRNA-seq, spatial transcriptomics in mouse cortex

    PMID:41888776

    Open questions at the time

    • Whether human CEP170 variants cause neurodevelopmental disease awaits patient-based studies
    • Relative contributions of ciliary vs. centrosomal CEP170 functions to cortical development are not dissected

• Key unresolved questions include the structural basis of CEP170's multivalent scaffolding at subdistal appendages, whether CEP170 loss causes ciliopathy phenotypes in vivo, and how its Plk1-dependent mitotic phosphorylation regulates its diverse interactor recruitment.
• No high-resolution structure of CEP170 or its complexes
• Functional significance of individual Plk1 phosphorylation sites remains unmapped
• No human Mendelian disease directly attributed to CEP170 mutations