| 2009 |
The human Ska1 complex is a three-subunit complex (including Ska1 and Rama1/Ska3) that localizes to the outer kinetochore and spindle microtubules. Reconstituted Ska1 complex possesses two separable biochemical activities: direct microtubule binding through the Ska1 subunit, and microtubule-stimulated oligomerization imparted by the Rama1 subunit. The full complex forms assemblies on microtubules that facilitate processive movement of microspheres along depolymerizing microtubules. |
Biochemical reconstitution, microtubule co-sedimentation assay, bead motility assay on depolymerizing microtubules, siRNA depletion with chromosome segregation readout |
Developmental cell |
High |
19289083
|
| 2006 |
Ska1 and Ska2 form a complex; Ska1 is required for Ska2 stability in vivo. Ska1 associates with kinetochores following microtubule attachment during prometaphase. Depletion of either subunit causes loss of both from kinetochores, increased cold-sensitivity of kinetochore fibres, and a prolonged checkpoint-dependent metaphase-like arrest with Mad2 retention at kinetochores. |
siRNA depletion, live-cell imaging, immunofluorescence, cold-stability assay of kinetochore fibres |
The EMBO journal |
High |
17093495
|
| 2012 |
The Ska1 complex tracks with depolymerizing microtubule ends and binds both the straight microtubule lattice and curved protofilaments, whereas the Ndc80 complex binds only straight lattice and lacks tracking activity. The Ska1 complex imparts its tracking capability to the Ndc80 complex. A crystal structure of the Ska1 microtubule-binding domain (MTBD) was determined, revealing its interaction with microtubules and its regulation by Aurora B phosphorylation. |
Single-molecule TIRF tracking assay, cryo-EM, X-ray crystallography of Ska1 MTBD, Aurora B phosphorylation of MTBD with microtubule binding assay |
Developmental cell |
High |
23085020
|
| 2016 |
Ska3 modulates the microtubule-binding capability of the Ska complex by (i) directly interacting with tubulin monomers and (ii) allosterically interacting with tubulin-contacting regions of Ska1. Perturbing either Ska3-microtubule or Ska3-Ska1 interactions reduces microtubule binding in vitro and delays anaphase onset in cells. |
In vitro microtubule binding assay with purified mutant complexes, co-IP of Ska3–Ska1 interaction, time-lapse imaging of anaphase onset |
Scientific reports |
High |
27667719
|
| 2016 |
EB1 interacts directly with Ska1 and facilitates Ska1 localization on microtubules in vertebrate cells. EB1 depletion reduces Ska1 recruitment onto microtubules and causes chromosome alignment defects. Together EB1 and Ska1 form extended structures on the microtubule lattice as revealed by structural studies. |
Co-IP (EB1–Ska1), EB1 siRNA depletion with Ska1 localization readout, in vitro microtubule co-sedimentation, structural EM of EB1–Ska complexes on microtubules, computational modelling |
Nature communications |
High |
27225956
|
| 2017 |
The Ska1 MTBD autonomously tracks growing microtubule ends in vitro in addition to depolymerizing ends. Multiple distinct surfaces of the Ska1 MTBD interact with diverse tubulin substrates: it binds the microtubule lattice, dolastatin-induced protofilament-like structures, and soluble tubulin heterodimers, and can promote assembly of oligomeric ring-like tubulin structures. Mutations on distinct MTBD surfaces that disrupt soluble tubulin binding without preventing lattice binding compromise microtubule tracking and cause defective chromosome alignment and mitotic progression in cells. |
Single-molecule TIRF assay for tip tracking, in vitro microtubule binding with purified mutant Ska1, CRISPR/Cas9 replacement assay in cells with chromosome alignment readout |
Current biology : CB |
High |
29153323
|
| 2014 |
SKA1 localizes to centrosomes in addition to spindle microtubules and the outer kinetochore. Depletion of Ska1 causes failure of centrosome duplication, while Ska1 over-expression leads to centrosome amplification via induction of centriole over-duplication in human prostate epithelial cells, which is sufficient to convert cells to a tumourigenic state. |
siRNA depletion with centrosome duplication readout, Ska1 over-expression with centriole counting, immunofluorescence, transgenic mouse model, xenograft tumourigenicity assay |
The Journal of pathology |
Medium |
24827423
|
| 2016 |
Ska1 and DDA3 act as molecular linkers between spindle dynamics and kinetochore composition. DDA3 recruits Kif2a onto the mitotic spindle, and Ska1 subsequently targets Kif2a to the minus-end of spindle microtubules to facilitate spindle dynamics. DDA3 also targets Ska1 to kinetochores to stabilize end-on attachment. |
Co-IP (Ska1–DDA3–Kif2a), siRNA depletion, immunofluorescence localization of Kif2a on spindle minus-ends |
Biochemical and biophysical research communications |
Medium |
26797278
|
| 2019 |
SKA1 interacts with the DNA-directed RNA polymerase II subunit RPB3. In MTX-sensitive cells, RPB3 binds the FPGS gene promoter and drives FPGS transcription upon MTX treatment; this is blocked in SKA1-overexpressing cells through formation of an inhibitory SKA1–RPB3 complex, causing downregulation of FPGS and de novo MTX resistance. ChIP confirmed RPB3 binding to the FPGS promoter. |
Co-IP (SKA1–RPB3), ChIP of RPB3 on FPGS promoter, siRNA knockdown of SKA1 to restore MTX sensitivity, Western blot for FPGS |
The FEBS journal |
Medium |
30851225
|
| 2019 |
PPARγ directly binds to a predicted response element in the SKA1 gene promoter and transcriptionally upregulates SKA1 expression. Under diabetogenic conditions (high glucose, palmitic acid, insulin), PPARγ-driven SKA1 expression promotes centrosome amplification; knockdown of PPARγ blocks the treatment-induced increase in SKA1, while knockdown of SKA1 does not affect PPARγ levels. |
ChIP (PPARγ binding to SKA1 promoter), PPARγ inhibitor/siRNA with SKA1 mRNA and protein readout, centrosome amplification assay |
Journal of cellular physiology |
Medium |
30989671
|
| 2020 |
SKA1 enhances pancreatic cancer cell migration by activating Cdc42 to remodel the actin cytoskeleton. iTRAQ proteomics identified downstream proteins of SKA1, and Cdc42 inhibition (ZCL278) or actin perturbation (cytochalasin B) reversed SKA1-induced morphology and migration changes. |
iTRAQ quantitative proteomics, Cdc42 inhibitor (ZCL278), cytochalasin B treatment, immunoblotting and immunofluorescence, in vivo xenograft |
Cell proliferation |
Medium |
32232899
|
| 2022 |
Ska1 interacts with EB1 through a conserved motif in its N-terminal disordered loop region; Ska1 binds the C-terminal region of the EB1 dimer. Disruption of this interaction (deletion or mutation of the motif) abolishes Ska complex recruitment to kinetochores and induces chromosome alignment defects without affecting Ska complex assembly. NMR showed the Ska1 motif binds EB1 residues that are shared binding sites for other plus-end targeting proteins. |
NMR spectroscopy (Ska1 motif–EB1 interaction), atomic-force microscopy imaging, site-directed mutagenesis with kinetochore localization readout, chromosome alignment assay |
The Journal of biological chemistry |
High |
36592928
|
| 2022 |
SKA1 interacts specifically with scaffold attachment factor B (SAFB), and this interaction mediates transcriptional repression of DUSP6, promoting ccRCC metastasis. SKA1 knockdown reduces cancer cell motility in vitro and in vivo. |
Co-IP (SKA1–SAFB), SKA1 knockdown with motility/invasion assay, in vivo metastasis model |
Aging |
Low |
36462498
|
| 2023 |
Cdt1 (DNA replication licensing factor) directly interacts with the Ska1 complex, and this interaction is required for recruiting Cdt1 to kinetochores and spindle microtubules. Cdk1 phosphorylation of Cdt1 is critical for Ska1 binding, kinetochore-microtubule attachments, and mitotic progression. Cdt1 synergizes with Ndc80 and Ska1 to form a diffusive, tripartite Ndc80–Cdt1–Ska1 complex that processively tracks dynamic microtubule plus-ends in vitro. |
Auxin-inducible degron for conditional Cdt1 depletion, co-IP (Cdt1–Ska1), in vitro microtubule binding with reconstituted tripartite complex, single-molecule tip-tracking assay, Cdk1 phosphorylation assay with phospho-mimetic/dead mutants |
The Journal of cell biology |
High |
37265445
|
| 2023 |
lncRNA MRVI1-AS1 recruits RNA-binding protein CELF2 to bind and stabilize SKA1 mRNA, increasing SKA1 protein expression in HCC cells. RIP assay confirmed direct interactions between CELF2 and both MRVI1-AS1 and SKA1 mRNA. MRVI1-AS1 expression is induced by hypoxia through a HIF-1-dependent pathway. |
RNA immunoprecipitation (RIP), actinomycin D mRNA stability assay, microarray mRNA expression analysis, dual luciferase assay, rescue experiments |
World journal of surgical oncology |
Medium |
36973749
|
| 2025 |
Oligomeric assemblies of Ska and Ndc80 complexes stabilize microtubule ends against shortening by strengthening lateral contacts between tubulin protofilaments at microtubule plus-ends, as visualized by cryoET. A point mutation in the Ska1 MTBD that does not affect individual Ska1–microtubule binding but abolishes Ska–Ska interactions disrupts stable kinetochore–microtubule attachments both in vitro and in vivo, demonstrating that cooperative Ska oligomerization with Ndc80 is required for stable attachments. |
Cryo-electron tomography (cryoET), site-directed mutagenesis of Ska1 MTBD, in vitro microtubule attachment assay, cellular assay of kinetochore-microtubule attachments |
bioRxivpreprint |
High |
bio_10.1101_2025.07.06.663352
|