Affinage

STIL

SCL-interrupting locus protein · UniProt Q15468

Length
1287 aa
Mass
143.0 kDa
Annotated
2026-06-10
86 papers in source corpus 35 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

STIL is a core centriole duplication factor that is recruited asymmetrically to the nascent procentriole in S phase, where it acts as both a scaffold and an allosteric activator of the master centriolar kinase PLK4 (PMID:22020124, PMID:25342035, PMID:26101219). Direct binding of STIL to PLK4 activates the kinase by promoting autophosphorylation of its activation loop, and PLK4 in turn phosphorylates STIL at multiple sites: STAN-motif phosphorylation drives the STIL–SAS6 interaction that initiates cartwheel assembly, while phosphorylation at S428 promotes STIL–CPAP binding to link the cartwheel to the centriole wall (PMID:25342035, PMID:26101219, PMID:31115335). STIL engages PLK4 bimodally—its coiled-coil region stabilizes PLK4 at the procentriole through Polo-box 3 while a C-terminal element drives autophosphorylation and degradation of adjacent PLK4—thereby restricting procentriole formation to a single site per parent centriole (PMID:26188084, PMID:29898389, PMID:31533936). STIL function requires its central coiled-coil-mediated oligomerization for centrosomal localization and centriole assembly (PMID:27075531, PMID:37834064), and it nucleates a wider assembly network through direct interactions with CPAP/CENPJ, hSAS6, CEP85, and RTTN (PMID:22020124, PMID:24052813, PMID:28811500, PMID:29712910). Because unrestrained STIL drives centriole amplification, its levels are tightly cell-cycle controlled: CDK1–CyclinB sequesters STIL in mitosis to block premature PLK4 complex formation, and STIL is degraded by APC/C(Cdc20/Cdh1) via a KEN box, by SCF-βTrCP via a CDK2-regulated DSG motif, and by FBXW7 acting on the STIL–SAS6 complex, while USP9X (localized by SFI1) deubiquitylates and stabilizes STIL in S phase (PMID:24485834, PMID:27112295, PMID:29445034, PMID:31197030, PMID:41453690). STIL-dependent centriole formation is required for primary cilium assembly and downstream Hedgehog signaling, and for genome stability in stem cells, where its loss triggers p53-dependent differentiation (PMID:22349705, PMID:25486474, PMID:30197118). Beyond centriole biogenesis, STIL scaffolds an ARHGEF7(β-PIX)–PAK1 complex at lamellipodia to promote Rac1 activation, actin remodeling, and directional cell migration, and supports dendritic spine formation through ARHGEF7-dependent Rac1 activity (PMID:31754215, PMID:32107292, PMID:39851490).

Mechanistic history

Synthesis pass · year-by-year structured walk · 33 steps
  1. 2011 High

    Established STIL as a procentriole assembly factor by placing it within the SAS6–CPAP module and showing it is required for their centriolar loading.

    Evidence Reciprocal Co-IP, siRNA depletion, overexpression, and immunofluorescence in human cells

    PMID:22020124

    Open questions at the time
    • Molecular basis of asymmetric daughter-centriole targeting unresolved
    • Order of recruitment relative to PLK4 not defined
  2. 2011 Medium

    Linked STIL-dependent centriole formation to spindle positioning, connecting it to the microcephaly (MCPH) phenotype of CPAP loss.

    Evidence siRNA depletion with micropattern spindle-orientation assay

    PMID:22100914

    Open questions at the time
    • Direct molecular role of STIL in spindle orientation versus indirect centriole effect not separated
  3. 2011 Medium

    Identified an early, non-centriolar STIL function regulating mitotic progression via Chfr/Plk1 stability.

    Evidence Knockout/siDNA, rescue, and ubiquitination assays in mouse fibroblasts

    PMID:21245198

    Open questions at the time
    • Mechanism by which STIL controls Chfr auto-ubiquitination unknown
    • Relationship to STIL's centriolar role unclear
  4. 2012 High

    Defined the cell-cycle behavior of STIL—recruitment at duplication onset and APC/C-dependent removal through mitosis—and showed overexpression drives centriole amplification.

    Evidence RNAi, time-lapse imaging, immuno-EM, and APC/C pathway manipulation across two independent studies

    PMID:22349698 PMID:22349705

    Open questions at the time
    • Degron sequences not yet mapped
    • Coupling of degradation timing to procentriole completion undefined
  5. 2013 High

    Provided the structural basis for STIL–CPAP recognition and showed a disease mutation disrupts it, establishing the interaction as functionally essential.

    Evidence X-ray crystallography of the CPAP TCP domain–STIL motif, ITC, and centriole duplication assays in U2OS cells

    PMID:24052813

    Open questions at the time
    • Phospho-regulation of this interface not yet known at this stage
  6. 2013 Medium

    Characterized the STIL central domain as intrinsically disordered, rationalizing its capacity for multiple binding partners.

    Evidence NMR, circular dichroism, SEC, and limited proteolysis

    PMID:24022511

    Open questions at the time
    • Functional consequences of disorder in cells not directly tested
  7. 2014 High

    Established the reciprocal PLK4–STIL relationship: STIL scaffolds SAS6 recruitment, PLK4 phosphorylation enables this, and centriolar STIL feeds back to restrict PLK4 to a single site.

    Evidence Co-IP, in vitro kinase assays, phospho-site mapping, and live imaging

    PMID:25342035

    Open questions at the time
    • Identity of the negative-feedback effector element not yet resolved
    • Direct phospho-sites driving SAS6 binding not fully mapped
  8. 2014 High

    Dissected STIL degradation into CDK1-driven centrosome dissociation followed by APC/C/KEN-box proteasomal turnover, and tied KEN-box loss to MCPH-associated amplification.

    Evidence Time-lapse imaging, APC/C and proteasome inhibition, KEN-box mutants, flow cytometry

    PMID:24485834

    Open questions at the time
    • How CDK1 triggers translocation mechanistically unclear
  9. 2014 High

    Connected STIL-dependent centriole formation to ciliogenesis and Hedgehog signaling and demonstrated de novo centriole generation upon STIL re-expression in null cells.

    Evidence FIB-SEM ultrastructure, Hedgehog reporter assays, and genetic rescue in Stil-/- cells/embryos

    PMID:22349705 PMID:25486474

    Open questions at the time
    • Whether STIL acts directly in Hh signaling beyond enabling cilia not separated here
  10. 2014 Low

    Reported a direct, but weakly validated, STIL link to Hedgehog components SUFU and GLI1.

    Evidence Single Co-IP with overexpression/knockdown and target-gene qPCR in PC12 cells

    PMID:24853807

    Open questions at the time
    • Single Co-IP without mutagenesis or reciprocal validation
    • Cilium-independent Hh role not established
  11. 2015 High

    Resolved the activation logic: STIL binding directly activates PLK4 via activation-loop autophosphorylation, and activated PLK4 then phosphorylates STIL to drive SAS6 binding and cartwheel initiation.

    Evidence Analog-sensitive PLK4 chemical genetics, in vitro kinase assays, Co-IP in gene-edited human cells

    PMID:25701666 PMID:26101219

    Open questions at the time
    • Stoichiometry of the active complex not defined
    • Spatial trigger for initial STIL recruitment unresolved
  12. 2015 High

    Defined the structural mode of STIL–PLK4 binding, identifying STIL as the first PLK4 Polo-box 3 partner via coiled-coil mimicry.

    Evidence NMR, X-ray crystallography, structure-guided mutagenesis, and centriole duplication assays

    PMID:26188084

    Open questions at the time
    • Interplay between STIL oligomerization and PLK4 binding only partially defined
  13. 2016 High

    Showed CDK1–CyclinB gates duplication timing by binding STIL in mitosis to prevent premature PLK4–STIL complex formation.

    Evidence Co-IP, in vitro kinase assays, and cell-cycle synchronization epistasis

    PMID:27112295

    Open questions at the time
    • CDK1 phospho-sites on STIL not fully mapped
  14. 2016 High

    Defined the coiled-coil oligomerization determinants of STIL required for centrosomal localization and both canonical and de novo centriole assembly.

    Evidence CD spectroscopy, SEC, mutagenesis, and reconstitution in Stil-/- MEFs

    PMID:27075531

    Open questions at the time
    • Oligomeric state in the assembling procentriole in vivo not resolved
  15. 2016 Medium

    Identified zinc-dependent conformational regulation of STIL's N-terminal domain and disordered region promoting oligomerization.

    Evidence CD, SEC, ITC, and fluorescence spectroscopy

    PMID:30155058

    Open questions at the time
    • No in vivo functional follow-up of zinc binding
    • Physiological relevance of zinc regulation untested
  16. 2017 High

    Placed RTTN downstream of STIL in the assembly hierarchy via a direct interaction disrupted by a microcephaly mutation.

    Evidence Co-IP, CRISPR KO, super-resolution/EM, and mutant pulldown

    PMID:28811500

    Open questions at the time
    • Structural basis of STIL–RTTN interface undefined
  17. 2018 High

    Identified CEP85 as a direct STIL partner required for STIL centriolar targeting and PLK4 activation, extending the upstream recruitment network.

    Evidence BioID, crystallography, structure-guided mutagenesis, Co-IP, and duplication assay

    PMID:29712910

    Open questions at the time
    • How CEP85 cooperates with CDK1/PLK4 timing not integrated
  18. 2018 High

    Resolved the bimodal STIL–PLK4 interaction—coiled-coil stabilization versus C-terminal TIM-domain-driven PLK4 degradation—as the basis for single-site procentriole restriction.

    Evidence Co-IP, in vitro kinase assays, domain mapping, truncation mutants, and live imaging

    PMID:29898389

    Open questions at the time
    • Quantitative threshold distinguishing positive from negative regulation undefined
  19. 2018 High

    Added SCF-βTrCP as an interphase-wide STIL degradation pathway acting through a phosphorylated DSG motif and counteracted by CDK2.

    Evidence Proteomics, Co-IP, in vivo phospho-analysis, CDK2 inhibition, and DSG mutagenesis

    PMID:29445034

    Open questions at the time
    • Kinase phosphorylating the DSG degron not identified
  20. 2018 Medium

    Demonstrated STIL is essential for genome stability and pluripotency maintenance, with loss triggering p53-dependent differentiation.

    Evidence STIL siRNA and PLK4 inhibition in hESCs/hiPSCs with flow cytometry and protein analysis

    PMID:30197118

    Open questions at the time
    • Mechanistic link between centrosome loss and p53 activation not dissected
  21. 2019 High

    Defined a second PLK4 phospho-site on STIL (S428) that drives STIL–CPAP binding, linking cartwheel to centriole wall, conserved to Drosophila.

    Evidence In vitro kinase assays, phospho-mutants, Co-IP, structure-guided mutagenesis, and Drosophila conservation

    PMID:31115335

    Open questions at the time
    • Temporal coordination of STAN-motif versus S428 phosphorylation unresolved
  22. 2019 High

    Identified a STIL stabilization arm: SFI1-localized USP9X deubiquitylates STIL in S phase, validated in patient cells.

    Evidence Co-IP, deubiquitylation assay, and USP9X loss-of-function patient cells

    PMID:31197030

    Open questions at the time
    • Balance between USP9X and the multiple E3 ligases not quantified
  23. 2019 Medium

    Provided endogenous-protein kinetics confirming that the STIL–HsSAS6 cartwheel exerts negative feedback attenuating centriolar PLK4.

    Evidence Live imaging of CRISPR knock-in proteins, quantitative tracking, depletion, and mathematical modeling

    PMID:31533936

    Open questions at the time
    • Molecular mechanism of feedback distinct from TIM-domain effect not reconciled
  24. 2019 Medium

    Revealed a centriole-independent STIL function: scaffolding the ARHGEF7–PAK1 complex at lamellipodia to drive Rac1-dependent cancer cell migration.

    Evidence Co-IP of ternary complex, siRNA knockdown, migration assays, and Rac1 FRET biosensor

    PMID:31754215

    Open questions at the time
    • Single lab; whether centriolar and migratory pools of STIL are distinct unresolved
  25. 2020 Medium

    Clarified that PLK4 autophosphorylation initiates its ring-to-dot condensation while STIL reinforces the condensate to enable SAS6 recruitment.

    Evidence Photoconvertible PLK4 live imaging, catalytic mutant, depletion, and condensate assays

    PMID:33323015

    Open questions at the time
    • Biophysical nature of the condensate in physiological cells not fully defined
  26. 2020 Medium

    Extended the migratory role by showing PLK4 recruits CEP85 and STIL to the leading edge to promote ARP2 phosphorylation and directional migration.

    Evidence Co-IP, interface mutagenesis, knockdown, migration and phosphorylation assays

    PMID:32107292

    Open questions at the time
    • Direct kinase–substrate relationship to ARP2 not established
  27. 2022 Medium

    Used the Drosophila ortholog to show Cdk/Cyclin phosphorylation of Ana2/STIL slows its diffusion to terminate daughter centriole growth at the correct time.

    Evidence FCS in Drosophila embryos, phospho-mutant expression, live imaging

    PMID:35861803

    Open questions at the time
    • Conservation of this diffusion-based timing mechanism in human STIL untested
  28. 2022 Medium

    Proposed an oncogenic nuclear STIL function partnering FOXM1 to drive metastasis, with HIF1α transcriptionally inducing STIL under hypoxia.

    Evidence ChIP-qPCR, Co-IP, RNA-seq, reporter assays, and xenograft metastasis

    PMID:35365182

    Open questions at the time
    • Mechanism of nuclear STIL translocation unclear
    • Separation from centriolar role not established
  29. 2023 Medium

    Quantified STIL coiled-coil self-association equilibria and resolved dimeric and tetrameric antiparallel structures essential for activity.

    Evidence Analytical ultracentrifugation, fluorescence, CD, and X-ray crystallography

    PMID:37834064

    Open questions at the time
    • Oligomeric state at the procentriole in vivo not directly observed
  30. 2025 Medium

    Added FBXW7-mediated degradation of the STIL–SAS6 complex as a PLK4-coupled negative feedback limiting overduplication.

    Evidence Co-IP, in vitro ubiquitination, PLK4 inhibition, FBXW7 depletion, centriole counting

    PMID:41453690

    Open questions at the time
    • Degron site and phospho-dependence on STIL not fully mapped
    • Single lab
  31. 2025 Medium

    Identified a neuronal STIL function supporting dendritic spine formation through coiled-coil-mediated ARHGEF7 binding and Rac1 activation.

    Evidence Co-IP, in vivo/in vitro shRNA knockdown, FRET Rac1 assay, Rac1/Cdc42 rescue, domain mutagenesis

    PMID:39851490

    Open questions at the time
    • Relationship to centriolar function in post-mitotic neurons unclear
  32. 2024 Low

    Proposed a STIL–BRCA1 interaction whose disruption by a cancer mutation redistributes BRCA1 and causes centrosome amplification and DNA damage.

    Evidence Co-IP, S76L overexpression, immunofluorescence, DNA damage and rescue assays

    PMID:41749477

    Open questions at the time
    • Co-IP and rescue in single paper without in vitro reconstitution
    • Direct versus indirect BRCA1 effect not separated
  33. 2025 Low

    Reported a hepatocellular carcinoma role in which STIL–FOXM1 co-occupy the SF3A3 promoter and modulate p53.

    Evidence Co-IP, ChIP-qPCR, knockdown, and xenograft model

    PMID:39825314

    Open questions at the time
    • Mechanistic details limited; direct transcriptional role of STIL not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple STIL degradation pathways, deubiquitylation, oligomerization, and PLK4 feedback loops are quantitatively integrated to ensure exactly one procentriole per parent remains unresolved, as does whether the migratory, neuronal, and nuclear oncogenic functions use the same molecular pool and binding surfaces as the centriolar role.
  • No unified quantitative model coupling activation, feedback, and degradation
  • Centriolar versus non-centriolar STIL pools not physically distinguished
  • Structural basis of full STIL–PLK4 active assembly incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0008092 cytoskeletal protein binding 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005815 microtubule organizing center 3 GO:0005634 nucleus 2 GO:0005856 cytoskeleton 2 GO:0005929 cilium 2
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 3
Partners
ARHGEF7CEP85CPAPPAK1PLK4RTTNSAS6USP9X
Complex memberships
ARHGEF7(β-PIX)-PAK1-STIL complexSTIL-PLK4 complexSTIL-SAS6 cartwheel complex

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 STIL localizes asymmetrically to the daughter centriole and is required for procentriole formation. STIL directly interacts with CPAP/CENPJ and forms a complex with hSAS6. STIL depletion inhibited centriole duplication, Plk4-induced centriole amplification, and CPAP-induced centriole elongation, and caused failure to localize hSAS6 and CPAP to the nascent procentriole. hSAS6 depletion also hindered STIL targeting, indicating mutual dependence for centriolar localization. Co-immunoprecipitation, siRNA depletion, overexpression, immunofluorescence microscopy The EMBO journal High 22020124
2011 STIL is essential for centriole formation and proper spindle positioning in human cells. Conditions mimicking CPAP MCPH mutations compromise centriole formation and correlate with randomized spindle position, and STIL depletion phenocopies this defect. siRNA depletion, adhesive micropatterns for spindle positioning assay, immunofluorescence Journal of cell science Medium 22100914
2012 STIL is required for centriole duplication in human cells; its overexpression triggers formation of multiple daughter centrioles. STIL is recruited to nascent daughter centrioles at onset of duplication and degraded in an APC/C(Cdc20-Cdh1)-dependent manner upon passage through mitosis. RNA interference, fluorescence time-lapse imaging, immunoelectron microscopy Journal of cell science High 22349698
2012 STIL is required for SAS6 recruitment to centrioles and interacts with CPAP. Stil-/- mouse embryonic fibroblasts lack primary cilia, a phenotype rescued by restoration of STIL expression, linking STIL-dependent centriole formation to ciliogenesis. siRNA depletion, overexpression, Stil knockout MEFs, immunofluorescence, rescue experiments Journal of cell science High 22349705
2013 Crystal structures of the CPAP TCP domain in complex with a short conserved STIL motif reveal a 1:1 complex. The TCP domain is a novel proline-recognition domain. A microcephaly mutation in CPAP (E1235V) compromises this complex. Point mutations in the STIL binding motif abolish centriole duplication in vivo. X-ray crystallography, isothermal titration calorimetry, point mutagenesis, centriole duplication assay in U2OS cells eLife High 24052813
2014 Plk4 and STIL form a protein complex that provides a scaffold for recruiting HsSAS-6 at the onset of procentriole formation. Plk4 phosphorylates STIL to facilitate the STIL/HsSAS-6 interaction and centriolar loading of HsSAS-6. Centriolar STIL exerts negative feedback on Plk4's bimodal centriolar distribution, restricting procentriole formation to one site per parental centriole. Co-immunoprecipitation, in vitro kinase assay, phosphorylation site mapping, overexpression and depletion in human cells, live imaging Nature communications High 25342035
2014 STIL is degraded via the APC/C-proteasome pathway in a two-step process: CDK1 triggers STIL translocation from centrosomes to cytoplasm at nuclear envelope breakdown, followed by APC/C(Cdc20/Cdh1)-dependent proteasomal degradation. A C-terminal KEN box in STIL is critical for its degradation. MCPH mutations that delete this KEN box render STIL resistant to degradation and cause centriole amplification. Fluorescence time-lapse imaging, APC/C inhibition, proteasome inhibition, mutant STIL constructs, flow cytometry Current biology : CB High 24485834
2015 Direct binding of STIL to PLK4 activates PLK4 by promoting self-phosphorylation of the kinase activation loop. PLK4 activity is required for STIL recruitment to the centriole. PLK4 then phosphorylates STIL to promote direct binding of STIL to the C terminus of SAS6, initiating cartwheel assembly. Chemical genetic system (ATP analogue-sensitive Plk4 allele in gene-edited human cells), in vitro kinase assays, Co-IP, FACS cell cycle analysis The Journal of cell biology High 26101219
2015 STIL interacts with Plk4 in vivo; the STIL fragment containing the coiled-coil domain and STAN motif shows the strongest binding affinity to Plk4. Plk4 phosphorylates STIL at specific C-terminal sites and this phosphorylation is required to trigger centriole duplication. Co-immunoprecipitation, in vitro kinase assay, phosphorylation site identification by mass spectrometry, dominant-negative phospho-mutant overexpression Biology open Medium 25701666
2015 STIL interacts via its coiled-coil region (STIL-CC) with PLK4 Polo-box 3 (PB3) — the first identified PB3 interaction partner — and also uses a secondary interaction site in PLK4 L1. NMR and crystal structures reveal a novel coiled-coil mimicry mode of Polo-box–peptide interaction. Structure-guided STIL mutants disrupt PLK4 binding and impair centriole duplication in vivo. STIL oligomerization interplays with PLK4 binding. NMR spectroscopy, X-ray crystallography, structure-guided mutagenesis, Co-IP, centriole duplication assay eLife High 26188084
2016 CDK1-CyclinB binds STIL in mitosis and prevents formation of the PLK4-STIL complex, thereby blocking STIL phosphorylation by PLK4 and preventing untimely onset of centriole biogenesis. After CDK1 inactivation upon mitotic exit, PLK4 can bind and phosphorylate STIL to allow procentriole assembly in S phase. Co-immunoprecipitation, in vitro kinase assay, overexpression/depletion experiments, cell cycle synchronization Current biology : CB High 27112295
2016 The central coiled-coil domain (CCD) of STIL mediates oligomerization via eight specific hydrophobic residues. Mutations in these residues destabilize the coiled-coil and impair centrosomal localization of STIL. STIL oligomerization is required for both canonical centriole duplication and de novo centriole biogenesis in STIL-null mouse embryonic fibroblasts. Circular dichroism spectroscopy, size exclusion chromatography, mutagenesis, reconstitution in Stil-/- MEFs Scientific reports High 27075531
2017 RTTN directly interacts with STIL and acts downstream of STIL-mediated centriole assembly. RTTN is recruited to the proximal end of the procentriole at early S phase. The microcephaly mutant RTTN(A578P) shows reduced affinity for STIL binding and blocks centriole assembly. Co-immunoprecipitation, super-resolution and electron microscopy, CRISPR/Cas9 knockout, pulldown with mutant proteins Nature communications High 28811500
2018 STIL binds PLK4 in a bimodal manner: the conserved short coiled-coil region stabilizes PLK4 at the procentriole site (positive regulation), while the C-terminal TIM domain promotes autophosphorylation and degradation of adjacent PLK4 (negative regulation). This bimodal interaction restricts procentriole formation to one site per parental centriole. Co-immunoprecipitation, in vitro kinase assay, domain-mapping pulldown, overexpression of truncation mutants, live imaging Cell reports High 29898389
2018 CEP85 directly interacts with STIL through a conserved interface involving a previously uncharacterized STIL domain. This interaction is essential for efficient centriolar targeting of STIL, PLK4 activation, and daughter centriole assembly. Structure-guided mutational analyses confirmed that the CEP85-STIL interaction interface is functionally critical in vivo. Protein proximity mapping (BioID), X-ray crystallography, structure-guided mutagenesis, Co-IP, centriole duplication assay Nature communications High 29712910
2018 SCF-βTrCP E3 ubiquitin ligase binds STIL via a DSG motif (phosphorylated at serine 395 in vivo) and mediates STIL degradation throughout interphase. CDK2 activity protects STIL against SCF-βTrCP-mediated degradation. Mutations in the DSG motif cause massive centrosome amplification. Proteomics, co-immunoprecipitation, in vivo phosphorylation analysis, CDK2 inhibition, DSG motif mutagenesis, centrosome counting Open biology High 29445034
2019 PLK4 phosphorylates STIL on a conserved site S428 to promote STIL binding to CPAP. This phospho-dependent interaction is conserved in Drosophila and facilitates stable incorporation of both STIL and CPAP into the centriole. PLK4 thus phosphorylates STIL in two regions: STAN motif phosphorylation enables STIL-SAS6 binding for cartwheel assembly, while S428 phosphorylation enables STIL-CPAP binding to link the cartwheel to the centriole wall. In vitro kinase assay, phospho-specific mutant analysis, Co-IP, structure-guided mutagenesis, Drosophila conservation assay eLife High 31115335
2019 SFI1 interacts with USP9X and localizes it to the centrosome during S phase. USP9X deubiquitylates STIL, protecting it from degradation. Cells from USP9X loss-of-function patients have reduced STIL levels, confirming the physiological relevance of this stabilization pathway. Co-immunoprecipitation, deubiquitylation assay, patient-derived cells, centrosome analysis The Journal of cell biology High 31197030
2019 STIL forms a ternary complex with ARHGEF7 (β-PIX) and PAK1 and accumulates with these proteins at lamellipodia protrusions of motile cells. STIL knockdown reduces ARHGEF7-PAK1 complex accumulation in membrane ruffles, attenuates PAK1 substrate phosphorylation, impairs cortical actin remodeling, and reduces Rac1 activity at the migrating front, thereby impairing cancer cell migration. Co-immunoprecipitation, siRNA knockdown, immunofluorescence, migration assay, Rac1 FRET biosensor Oncogene Medium 31754215
2011 Stil suppresses Chfr protein stability by increasing Chfr auto-ubiquitination, thereby reducing Chfr's substrate Plk1 levels. Mouse fibroblasts lacking Stil exhibit high Chfr, low Plk1, slow growth, low mitotic index, and absent centrosomes. Knockdown of Chfr or overexpression of Plk1 rescues the abnormal mitotic phenotypes of Stil-null fibroblasts. Knockout and siRNA depletion, rescue overexpression, ubiquitination assay, western blot, immunofluorescence Journal of cell science Medium 21245198
2014 Stil-/- mouse embryos lack centrioles and primary cilia (shown by focused ion beam scanning electron microscopy). Absence of primary cilia explains the loss of Hedgehog signaling in Stil-/- cells. Re-expression of STIL or MCPH-compatible STIL mutants induces non-templated de novo generation of centrioles in Stil-/- cells. Focused ion beam scanning electron microscopy, Hedgehog pathway reporter assay, genetic rescue with exogenous STIL expression Cell cycle (Georgetown, Tex.) High 25486474
2013 The central domain of STIL is intrinsically disordered and mediates its protein-protein interactions. This intrinsic disorder provides conformational flexibility required for STIL's multiple binding activities. Biophysical methods (NMR, circular dichroism, size exclusion chromatography), limited proteolysis Chemical communications (Cambridge, England) Medium 24022511
2016 Zn2+ ions bind to both the structured N-terminal domain (NTD) and the intrinsically disordered region (IDR) of STIL. Zn2+ binding induces structural rearrangement of the NTD and promotes oligomerization of the IDR, suggesting zinc-dependent conformational changes regulate STIL activity and oligomerization. Circular dichroism spectroscopy, size exclusion chromatography, isothermal titration calorimetry, fluorescence spectroscopy Chemical science Medium 30155058
2019 Live-cell imaging of endogenously tagged proteins showed that centriolar Plk4 peaks and decreases in late G1, coinciding with STIL accumulation at centrioles; HsSAS6 then increases steeply at the procentriole site. Both STIL and HsSAS6 are necessary for attenuating Plk4 levels. Mathematical modeling supported a negative feedback effect of the STIL-HsSAS6 cartwheel complex on centriolar Plk4. Live-cell imaging of endogenously tagged proteins (CRISPR knock-in), quantitative tracking, mathematical modeling, siRNA depletion Biology open Medium 31533936
2020 Plk4 autophosphorylation is sufficient to initiate its ring-to-dot localization conversion around the centriole; STIL is not required for this initial step but greatly enhances Plk4's ability to generate a spherical condensate and recruit Sas6 once co-expressed. STIL-dependent reinforcement of the PLK4 condensate is essential for procentriole assembly. Photoconvertible mEOS-fused Plk4 live imaging, catalytically inactive Plk4 mutant, siRNA depletion, in vivo condensate assay in human cells and E. coli Cell cycle (Georgetown, Tex.) Medium 33323015
2022 Cdk/Cyclin-dependent phosphorylation of Ana2/STIL (Drosophila ortholog) reduces its cytoplasmic diffusion rate toward the end of S-phase, limiting daughter centriole growth. A non-phosphorylatable Ana2 mutant allows daughters to grow for an extended period, demonstrating that Cdk/Cyclin activity on Ana2/STIL stops centriole elongation at the correct time. Fluorescence correlation spectroscopy in Drosophila embryos, phospho-mutant Ana2 expression, live imaging The Journal of cell biology Medium 35861803
2023 The STIL CCD peptide undergoes concentration-dependent oligomerization forming dimers (KD = 8 µM) and tetramers (KD = 68 µM). Crystal structures of CCD mutants reveal dimeric and tetrameric antiparallel coiled-coil structures. Disrupting STIL oligomerization via the CCD inhibits its activity in vivo. Analytical ultracentrifugation, fluorescence spectroscopy, circular dichroism, X-ray crystallography International journal of molecular sciences Medium 37834064
2025 FBXW7 SCF E3 ubiquitin ligase mediates degradation of the STIL-SAS6 cartwheel complex. Plk4 kinase activity is required for FBXW7-dependent STIL degradation. Phosphorylation of Plk4-targeting sites in STIL that drive centriole assembly (facilitating STIL-SAS6 interaction) also stabilizes FBXW7 binding to STIL, creating a negative feedback that limits centriole overduplication. FBXW7 depletion causes premature centriole duplication via STIL-SAS6 stabilization. Co-immunoprecipitation, in vitro ubiquitination assay, Plk4 kinase inhibition, FBXW7 depletion, centriole counting The Journal of biological chemistry Medium 41453690
2020 CEP85 and STIL are required for PLK4-driven directional cancer cell migration. PLK4 drives recruitment of CEP85 and STIL to the leading edge of cells to promote protrusive activity. Downregulation of CEP85 and STIL reduces ARP2 phosphorylation and impairs actin cytoskeleton reorganization and directional migration. Mutational and functional analyses, Co-IP, siRNA knockdown, migration assay, immunofluorescence at leading edge, phosphorylation assay Journal of cell science Medium 32107292
2025 STIL associates with ARHGEF7 in dendritic spines. Knockdown of Stil reduces dendritic spines in neurons in vitro and in vivo. This function depends on STIL's coiled-coil domain that mediates ARHGEF7 binding. STIL knockdown impairs Rac1 activation in spines, and overexpression of Rac1/Cdc42 compensates for STIL loss. Chemical LTP promotes STIL accumulation in spines. Co-immunoprecipitation, in vitro and in vivo shRNA knockdown, FRET-based Rac1 activity assay, rescue with Rac1/Cdc42, domain mutagenesis Cells Medium 39851490
2022 A subset of STIL translocates to the nucleus and associates with FOXM1 to promote tumor metastasis and stemness via FOXM1-mediated target genes. HIF1α directly binds the STIL promoter and upregulates STIL expression under hypoxia. Excess STIL activates the EMT pathway and enhances cancer cell migration and invasion. ChIP-qPCR (HIF1α binding to STIL promoter), Co-IP (STIL-FOXM1 interaction), RNA-seq, reporter assays, xenograft metastasis assay, siRNA depletion Journal of biomedical science Medium 35365182
2024 STIL interacts with BRCA1 and regulates its stability; a cancer-associated heterozygous missense mutation (S76L) in STIL disrupts this interaction and redistributes BRCA1 from the nucleus to centrosomes. STIL-S76L overexpression elevates centrosomal Aurora-A and PLK1 kinases, causing centrosome amplification and DNA damage. Mutant cells maintain pseudo-bipolar spindles via HSET-dependent centrosome clustering. Co-immunoprecipitation, overexpression of S76L mutant, immunofluorescence, DNA damage assay, rescue with WT BRCA1 FEBS letters Low 41749477
2018 Inactivation of PLK4 or STIL in human pluripotent stem cells leads to centrosome loss followed by p53-dependent upregulation, chromosome instability, reduction of pluripotency markers, and induction of differentiation. Loss of STIL function causes prolonged cell divisions and alterations in mitotic timing and protein turnover. PLK4 chemical inhibition, STIL siRNA knockdown in hESCs and hiPSCs, flow cytometry, immunofluorescence, western blot Stem cell reports Medium 30197118
2014 STIL functions through the Sonic hedgehog (Shh) signaling pathway: co-immunoprecipitation revealed that STIL interacts with Shh downstream components SUFU and GLI1. Overexpression of STIL increased Shh signaling and PC12 cell proliferation; knockdown inhibited Shh signaling and proliferation. Co-immunoprecipitation, overexpression and shRNA knockdown in PC12 cells, qPCR of Shh target genes Biochemical and biophysical research communications Low 24853807
2025 STIL interacts with FOXM1 and co-occupies the SF3A3 promoter (by ChIP-qPCR) to regulate SF3A3 transcription in hepatocellular carcinoma cells. STIL loss inhibits HCC malignant behavior partly by promoting p53 expression. Knockdown of FOXM1 enhances the anti-tumor effects of STIL loss. Co-IP, ChIP-qPCR, siRNA knockdown, xenograft tumor model Cell division Low 39825314

Source papers

Stage 0 corpus · 86 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Direct interaction of Plk4 with STIL ensures formation of a single procentriole per parental centriole. Nature communications 204 25342035
2011 The human microcephaly protein STIL interacts with CPAP and is required for procentriole formation. The EMBO journal 204 22020124
2009 Mutations in STIL, encoding a pericentriolar and centrosomal protein, cause primary microcephaly. American journal of human genetics 182 19215732
2015 Binding of STIL to Plk4 activates kinase activity to promote centriole assembly. The Journal of cell biology 165 26101219
2012 STIL is required for centriole duplication in human cells. Journal of cell science 149 22349705
2012 Cell-cycle-regulated expression of STIL controls centriole number in human cells. Journal of cell science 148 22349698
2016 The PLK4-STIL-SAS-6 module at the core of centriole duplication. Biochemical Society transactions 123 27911707
2015 Plk4-dependent phosphorylation of STIL is required for centriole duplication. Biology open 113 25701666
2015 STIL binding to Polo-box 3 of PLK4 regulates centriole duplication. eLife 110 26188084
2014 STIL microcephaly mutations interfere with APC/C-mediated degradation and cause centriole amplification. Current biology : CB 97 24485834
2011 Spindle positioning in human cells relies on proper centriole formation and on the microcephaly proteins CPAP and STIL. Journal of cell science 95 22100914
2013 Crystal structures of the CPAP/STIL complex reveal its role in centriole assembly and human microcephaly. eLife 87 24052813
2019 PLK4 promotes centriole duplication by phosphorylating STIL to link the procentriole cartwheel to the microtubule wall. eLife 71 31115335
2016 CDK1 Prevents Unscheduled PLK4-STIL Complex Assembly in Centriole Biogenesis. Current biology : CB 62 27112295
2020 Hsa_circ_0000069 Knockdown Inhibits Tumorigenesis and Exosomes with Downregulated hsa_circ_0000069 Suppress Malignant Transformation via Inhibition of STIL in Pancreatic Cancer. International journal of nanomedicine 56 33324055
2012 In silico prediction of a disease-associated STIL mutant and its affect on the recruitment of centromere protein J (CENPJ). FEBS open bio 47 23772360
2018 Bimodal Binding of STIL to Plk4 Controls Proper Centriole Copy Number. Cell reports 42 29898389
2011 The Stil protein regulates centrosome integrity and mitosis through suppression of Chfr. Journal of cell science 41 21245198
2017 Human microcephaly protein RTTN interacts with STIL and is required to build full-length centrioles. Nature communications 39 28811500
2018 Direct binding of CEP85 to STIL ensures robust PLK4 activation and efficient centriole assembly. Nature communications 38 29712910
2014 Lack of centrioles and primary cilia in STIL(-/-) mouse embryos. Cell cycle (Georgetown, Tex.) 35 25486474
2018 Autoamplification and Competition Drive Symmetry Breaking: Initiation of Centriole Duplication by the PLK4-STIL Network. iScience 34 30340068
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
2018 STIL balancing primary microcephaly and cancer. Cell death & disease 28 29352115
2015 Homozygous STIL mutation causes holoprosencephaly and microcephaly in two siblings. PloS one 28 25658757
2018 The subclonal complexity of STIL-TAL1+ T-cell acute lymphoblastic leukaemia. Leukemia 26 29556024
2010 STIL, a peculiar molecule from styles, specifically dephosphorylates the pollen receptor kinase LePRK2 and stimulates pollen tube growth in vitro. BMC plant biology 26 20175921
2014 STIL mutation causes autosomal recessive microcephalic lobar holoprosencephaly. Human genetics 25 25218063
2019 Knockdown of STIL suppresses the progression of gastric cancer by down-regulating the IGF-1/PI3K/AKT pathway. Journal of cellular and molecular medicine 23 31187582
2018 The SKP1-Cullin-F-box E3 ligase βTrCP and CDK2 cooperate to control STIL abundance and centriole number. Open biology 21 29445034
2022 STIL Promotes Tumorigenesis of Bladder Cancer by Activating PI3K/AKT/mTOR Signaling Pathway and Targeting C-Myc. Cancers 19 36497260
2016 Molecular basis of the STIL coiled coil oligomerization explains its requirement for de-novo formation of centrosomes in mammalian cells. Scientific reports 19 27075531
2022 A novel HIF1α-STIL-FOXM1 axis regulates tumor metastasis. Journal of biomedical science 18 35365182
2019 SFI1 promotes centriole duplication by recruiting USP9X to stabilize the microcephaly protein STIL. The Journal of cell biology 18 31197030
2019 Indispensable role of STIL in the regulation of cancer cell motility through the lamellipodial accumulation of ARHGEF7-PAK1 complex. Oncogene 18 31754215
2019 Feedback loops in the Plk4-STIL-HsSAS6 network coordinate site selection for procentriole formation. Biology open 17 31533936
2018 The human oncogene SCL/TAL1 interrupting locus (STIL) promotes tumor growth through MAPK/ERK, PI3K/Akt and AMPK pathways in prostate cancer. Gene 17 30453068
2014 Transcription of the SCL/TAL1 interrupting Locus (Stil) is required for cell proliferation in adult Zebrafish Retinas. The Journal of biological chemistry 16 24469449
2017 Novel STIL Compound Heterozygous Mutations Cause Severe Fetal Microcephaly and Centriolar Lengthening. Molecular syndromology 15 29230157
2023 STIL/AURKA axis promotes cell proliferation by influencing primary cilia formation in bladder cancer. Journal of translational medicine 14 37101292
2022 STIL Acts as an Oncogenetic Driver in a Primary Cilia-Dependent Manner in Human Cancer. Frontiers in cell and developmental biology 13 35155425
2020 Direct interaction between CEP85 and STIL mediates PLK4-driven directed cell migration. Journal of cell science 13 32107292
2019 STIL is upregulated in nasopharyngeal carcinoma tissues and promotes nasopharyngeal carcinoma proliferation, migration and invasion. Neoplasma 13 31607137
2017 A key centriole assembly interaction interface between human PLK4 and STIL appears to not be conserved in flies. Biology open 12 28202467
2015 StIL-17 gene polymorphisms in the development of pulmonary tuberculosis. International journal of clinical and experimental pathology 12 26045845
2019 Synchronous Cervical Minimal Deviation Adenocarcinoma, Gastric Type Adenocarcinoma and Lobular Endocervical Glandular Hyperplasia Along with STIL in Peutz-Jeghers Syndrome: Eliciting Oncogenesis Pathways. Turk patoloji dergisi 10 28832082
2017 Targeting the centriolar replication factor STIL synergizes with DNA damaging agents for treatment of ovarian cancer. Oncotarget 10 28423708
2013 The STIL protein contains intrinsically disordered regions that mediate its protein-protein interactions. Chemical communications (Cambridge, England) 10 24022511
2012 Functional expression of SCL/TAL1 interrupting locus (Stil) protects retinal dopaminergic cells from neurotoxin-induced degeneration. The Journal of biological chemistry 10 23166330
2023 Clinical Meaning of Stromal Tumor Infiltrating Lymphocytes (sTIL) in Early Luminal B Breast Cancer. Cancers 9 37345183
2021 The biological function and clinical significance of STIL in osteosarcoma. Cancer cell international 8 33858425
2021 STIL Endows Oncogenic and Stem-Like Attributes to Colorectal Cancer Plausibly by Shh and Wnt Signaling. Frontiers in oncology 8 34485108
2014 Characterization of the human oncogene SCL/TAL1 interrupting locus (Stil) mediated Sonic hedgehog (Shh) signaling transduction in proliferating mammalian dopaminergic neurons. Biochemical and biophysical research communications 8 24853807
2014 A prenatal presentation of severe microcephaly and brain anomalies in a patient with novel compound heterozygous mutations in the STIL gene found postnatally with exome analysis. Pediatric neurology 8 24986681
2020 RBM10 regulates centriole duplication in HepG2 cells by ectopically assembling PLK4-STIL complexes in the nucleus. Genes to cells : devoted to molecular & cellular mechanisms 7 31820547
2019 STIL: a multi-function protein required for dopaminergic neural proliferation, protection, and regeneration. Cell death discovery 7 31044090
2021 Circular RNA Circ-STIL Contributes to Cell Growth and Metastasis in Hepatocellular Carcinoma via Regulating miR-345-5p/AQP3 Axis. Digestive diseases and sciences 6 34231101
2022 Centriole growth is limited by the Cdk/Cyclin-dependent phosphorylation of Ana2/STIL. The Journal of cell biology 5 35861803
2020 Autophosphorylation-induced self-assembly and STIL-dependent reinforcement underlie Plk4's ring-to-dot localization conversion around a human centriole. Cell cycle (Georgetown, Tex.) 5 33323015
2018 Inactivation of PLK4-STIL Module Prevents Self-Renewal and Triggers p53-Dependent Differentiation in Human Pluripotent Stem Cells. Stem cell reports 5 30197118
2017 Influence of body mass index on survival in indolent and mantle cell lymphomas: analysis of the StiL NHL1 trial. Annals of hematology 5 28456850
2016 Differential effects of zinc binding on structured and disordered regions in the multidomain STIL protein. Chemical science 5 30155058
2014 Microcephaly: STIL(l) a tale of too many centrosomes. Current biology : CB 5 24556440
1992 Production of a negative regulator of IL-3 by bone marrow cells in response to the supernatant of IL-3-producing STIL-3 leukemia cells. Leukemia research 5 1405720
2021 Clinico-Hematological Profile and Copy Number Abnormalities in a Cohort of STIL-TAL1 and NUP214-ABL1 Positive Pediatric T-Cell Acute Lymphoblastic Leukemia. Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion 4 34744339
2015 A novel function of the human oncogene Stil: Regulation of PC12 cell toxic susceptibility through the Shh pathway. Scientific reports 4 26549353
2024 STIL facilitates the development and malignant progression of triple-negative breast cancer through activation of Fanconi anemia pathway via interacting with KLF16. Translational oncology 3 38823260
2024 STIL Overexpression Is Associated with Chromosomal Numerical Abnormalities in Non-Small-Cell Lung Carcinoma Through Centrosome Amplification. Current oncology (Toronto, Ont.) 3 39727708
2018 Origins of STIL-TAL1 fusion genes in children who later developed paediatric T-cell acute lymphoblastic leukaemia: An investigation of neonatal blood spots. Pediatric blood & cancer 3 29968961
2014 Centriole duplication: when PLK4 meets Ana2/STIL. Current biology : CB 3 25517369
2025 The MCPH7 Gene Product STIL Is Essential for Dendritic Spine Formation. Cells 2 39851490
2024 STIL overexpression shortens lifespan and reduces tumor formation in mice. PLoS genetics 2 39466849
2024 STIL enhances the development of lung adenocarcinoma by regulating the glycolysis pathway. Oncology research 2 39735672
2023 Molecular Mechanism of STIL Coiled-Coil Domain Oligomerization. International journal of molecular sciences 2 37834064
2020 Novel compound heterozygous variants in the STIL gene identified in a Chinese family with presentation of foetal microcephaly. European journal of medical genetics 2 33132204
2025 Interaction of STIL with FOXM1 regulates SF3A3 transcription in the hepatocellular carcinoma development. Cell division 1 39825314
2025 H3K18la Facilitates TRA2A-Mediated Alternative Splicing of STIL, Suppressing Ferroptosis and Cisplatin Treatment Sensitivity in Ovarian Cancer. Cancer research and treatment 1 40907573
2022 Prevalence of precursor lesions (P53 signature, SCOUT, STIL, STIC) in fallopian tubes resected for non-neoplastic causes. Indian journal of pathology & microbiology 1 35900489
2026 Disrupted STIL-BRCA1 axis causes centrosome amplification and genomic instability. FEBS letters 0 41749477
2026 Multi-omics analysis reveals the key role of STIL in Li-Fraumeni syndrome and osteosarcoma. NPJ precision oncology 0 42009739
2026 Comparison of Stromal Tumor-Infiltrating Lymphocyte (sTIL) Levels and Clinicopathological Features in Neoadjuvant-Naive HER2-Low and HER2-Negative Primary Breast Cancers. Medicina (Kaunas, Lithuania) 0 42195079
2025 Clinical, Immunologic, and Genetic Characteristics of T-lymphoblastic Leukemia with STIL-TAL1 Fusion. Clinical laboratory 0 40066532
2025 FBXW7 E3 ligase prevents centriole overduplication by degrading the Plk4 phosphorylated STIL-SAS6 cartwheel assembly. The Journal of biological chemistry 0 41453690
2024 An Incidental Fallopian Tube Focal Serous Tubal Intraepithelial Lesion (STIL) Discovered on a Postoperative Pathology Report Following Hysterectomy and Salpingectomy: A Case Report. Cureus 0 38910622
2023 The Role of Stromal Tumour Infiltrating Lymphocytes (sTIL) Intensity and Programmed Death Ligand 1 () Expression in Breast Cancer Response to Neoadjuvant Therapy in Cipto Mangunkusumo Hospital (CMH), Indonesia. Asian Pacific journal of cancer prevention : APJCP 0 37898851
2022 Yeast 2-hybrid assay for investigating the interaction between the centrosome proteins PLK4 and STIL. Methods in cell biology 0 35623713

Missed literature

Know a paper Affinage missed for STIL? Flag it for the maintainers and the community.

No submissions yet.