Affinage

NCKIPSD

NCK-interacting protein with SH3 domain · UniProt Q9NZQ3

Length
722 aa
Mass
79.0 kDa
Annotated
2026-06-10
100 papers in source corpus 22 papers cited in narrative 22 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

NCKIPSD (SPIN90/WISH/DIP) is an SH3- and proline-rich-domain adaptor that organizes actin cytoskeletal dynamics by directly engaging the Arp2/3 complex and scaffolding multiple actin regulators (PMID:11157975, PMID:16253999, PMID:32572169). It enhances N-WASP-induced Arp2/3 activation in a Cdc42-independent manner, and its own C-terminus binds both G-actin and the Arp2/3 complex to drive actin polymerization (PMID:11157975, PMID:16253999). Beyond promoting branched nucleation, NCKIPSD recruits the formin mDia1 to Arp2/3-nucleated filaments and forms a ternary SPIN90-Arp2/3-mDia1 complex that nucleates long, rapidly elongating unbranched filaments, biasing cortical networks toward a formin-dominated architecture (PMID:32572169). Through its SH3 domain and proline-rich region it links Nck, betaPIX/WASP/ERK1, IRSp53, syndapin, and dynamin I into adhesion- and growth-factor-responsive complexes that build lamellipodia and membrane ruffles and execute clathrin-mediated and EGFR endocytosis (PMID:11278500, PMID:14559906, PMID:19460367, PMID:16221862, PMID:16999739, PMID:24340049); in the endocytic pathway, ERK-dependent phosphorylation at Thr-242 enables NCKIPSD to bridge the GEF Gapex5 to inactive Rab5/GDI2 and activate Rab5 on endosomes (PMID:31358736). In neurons, NCKIPSD associates with PSD-95 and Shank at dendritic spines to promote spinogenesis and spine maturation, with Src-dependent tyrosine phosphorylation targeting it to spines and enhancing postsynaptic function, while NMDA-induced dephosphorylation by STEP61 releases cofilin to drive actin depolymerization and spine shrinkage (PMID:16990791, PMID:19302483, PMID:23342115, PMID:23765104). In fibroblasts, loss of NCKIPSD elevates Rho activity and impairs motility, and drives microtubule acetylation-dependent YAP nuclear translocation and ECM remodeling that activate cancer-associated fibroblasts (PMID:19778379, PMID:28652253, PMID:31637720). NCKIPSD was originally identified as the AF3p21 MLL fusion partner in therapy-related leukemia bearing t(3;11)(p21;q23) (PMID:10648423).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 2000 Medium

    Established NCKIPSD as a gene of clinical relevance by identifying it as a novel MLL fusion partner, defining its domain architecture (SH3, proline-rich domain, NLS) before any cytoskeletal function was known.

    Evidence Genomic cloning and fusion-junction sequencing from therapy-related leukemia cells with t(3;11)(p21;q23)

    PMID:10648423

    Open questions at the time
    • Does not establish a functional role for the fusion protein
    • Loss of the SH3 domain in the fusion leaves the chimera's mechanism undefined
  2. 2001 High

    Defined the core biochemical activity of NCKIPSD: it binds N-WASP via its SH3 domain and strongly potentiates N-WASP/Arp2/3-driven actin polymerization independent of Cdc42, establishing it as an actin nucleation regulator.

    Evidence In vitro Arp2/3 polymerization assays, co-IP, N-WASP-depleted brain extract rescue, and N-WASP mutant (H208D) cell assays

    PMID:11157975

    Open questions at the time
    • Did not resolve the N-WASP-independent route to Arp2/3 activation at the molecular level
    • Physiological trigger for the activity in cells not defined
  3. 2001 High

    Identified NCKIPSD as an Nck-binding adaptor localizing to sarcomere Z-discs, framing it as a structural scaffold whose perturbation disrupts cytoskeletal organization.

    Evidence Yeast two-hybrid, in vitro SH3-binding assays, immunofluorescence, and antibody microinjection in cardiac myocytes

    PMID:11278500

    Open questions at the time
    • Mechanism linking Nck binding to Z-disc maintenance not established
    • Cardiac function relevance untested
  4. 2003 High

    Connected NCKIPSD scaffolding to signaling by showing ERK1 phosphorylation regulates assembly of a betaPIX/WASP/SPIN90 complex with Nck in an adhesion-dependent manner.

    Evidence Yeast two-hybrid, in vitro binding, co-IP, ERK kinase assays, and adhesion manipulation

    PMID:14559906

    Open questions at the time
    • Specific ERK phospho-sites not mapped in this study
    • Downstream actin output of the complex not quantified
  5. 2005 High

    Demonstrated NCKIPSD's direct, autonomous Arp2/3 activity (C-terminus binds G-actin and Arp2/3) and tied it to growth-factor-induced cortical actin remodeling.

    Evidence siRNA knockdown, PDGF stimulation, in vitro Arp2/3 activation with C-terminal domain, actin comet tail coexpression

    PMID:16253999

    Open questions at the time
    • Relative contribution of direct versus N-WASP-mediated Arp2/3 activation in cells unresolved
    • Structural basis of C-terminal Arp2/3/G-actin binding unknown
  6. 2005 High

    Extended NCKIPSD function to membrane trafficking by showing it binds dynamin I and is required for synaptic vesicle endocytosis.

    Evidence Pull-down, reciprocal co-IP, knockdown/overexpression, FM-dye endocytosis assays and interaction-disruption rescue

    PMID:16221862

    Open questions at the time
    • Whether actin nucleation activity is required for the endocytic role not separated
    • Coupling to the dynamin fission step mechanistically undefined
  7. 2006 High

    Generalized the endocytic role to clathrin-mediated endocytosis via syndapin and clathrin binding, and placed NCKIPSD on Rab5/EEA1 early endosomes.

    Evidence Yeast two-hybrid, pull-down, co-IP, transferrin uptake with rescue, knockdown, and live-cell imaging

    PMID:16999739

    Open questions at the time
    • How NCKIPSD switches between dynamin and syndapin partners not defined
    • Vesicle-stage specificity of its action unclear
  8. 2006 High

    Established a neuronal structural role: NCKIPSD associates with PSD-95 and drives spinogenesis through an N-WASP-independent mechanism.

    Evidence Reciprocal co-IP, siRNA knockdown, overexpression spine morphometry, and chemical LTP-induced redistribution

    PMID:16990791

    Open questions at the time
    • Molecular identity of the N-WASP-independent actin pathway in spines not specified
    • Direct PSD-95 binding interface not mapped
  9. 2007 High

    Identified palladin as a determinant of NCKIPSD intracellular targeting, distinguishing NCKIPSD-dependent from Src/palladin-dependent cytoskeletal remodeling.

    Evidence Direct in vitro SH3-polyproline binding, co-IP, knockdown, and active-Src overexpression with colocalization

    PMID:17537434

    Open questions at the time
    • Functional consequence of palladin-directed targeting on actin output not quantified
    • Hierarchy of palladin versus other targeting cues unknown
  10. 2009 High

    Defined cooperative cytoskeletal and synaptic modules: NCKIPSD partners IRSp53 to drive Rac-dependent lamellipodia, and Shank to mediate spine maturation, with knockout altering PSD composition.

    Evidence Co-IP, siRNA knockdown, domain competition, knockout mice, and immunofluorescence across two studies

    PMID:19302483 PMID:19460367

    Open questions at the time
    • Whether IRSp53 and Shank modules are spatially distinct pools not addressed
    • Mechanism of Rac activation downstream of IRSp53 binding unresolved
  11. 2009 High

    Revealed NCKIPSD as a negative regulator of Rho controlling adhesion and motility, using knockout fibroblasts.

    Evidence Knockout MEFs with Rho activity assays, motility and adhesion readouts, stress-fiber imaging

    PMID:19778379

    Open questions at the time
    • Molecular mechanism by which NCKIPSD suppresses Rho not defined
    • Link between Rho regulation and Arp2/3 nucleation function unclear
  12. 2011 High

    Showed NCKIPSD supports neuronal growth-cone morphogenesis and Cdc42 activity, linking it to early neurite development.

    Evidence Knockout neurons, F-actin colocalization, growth-cone morphometry, Cdc42 activity assay

    PMID:21763308

    Open questions at the time
    • How NCKIPSD promotes Cdc42 activity mechanistically unknown
    • Relationship to its Cdc42-independent Arp2/3 activity not reconciled
  13. 2013 High

    Established Src-dependent tyrosine phosphorylation as the switch that targets NCKIPSD to spines and enhances synaptic function.

    Evidence In vitro/in vivo kinase assays, phospho-deficient/mimetic mutants, localization, and EPSC electrophysiology

    PMID:23342115

    Open questions at the time
    • Phospho-site(s) governing PSD-95/Shank binding not fully resolved
    • Upstream signals activating Src toward NCKIPSD undefined
  14. 2013 High

    Defined the reverse switch and a direct actin-depolymerization mechanism: STEP61 dephosphorylates NCKIPSD upon NMDA stimulation, releasing bound cofilin to drive spine shrinkage.

    Evidence NMDA stimulation, STEP61 identification, phospho-SPIN90/cofilin co-IP, phosphomimetic mutants, spine and cortactin/drebrin imaging

    PMID:23765104

    Open questions at the time
    • Structural basis of phospho-dependent cofilin sequestration not determined
    • How this integrates with NCKIPSD's Arp2/3-nucleating role in the same spine unclear
  15. 2013 High

    Connected NCKIPSD to receptor signaling output by showing it promotes EGFR endocytosis, with its loss stabilizing surface EGFR, elevating ERK1/2 and driving proliferation.

    Evidence Stable knockdown with EM, confocal endosome analysis, surface EGFR quantification, domain dissection, and proliferation assays

    PMID:24340049

    Open questions at the time
    • Step at which NCKIPSD acts in EGFR endosomal maturation not pinpointed here
    • Generality across other receptor cargoes untested
  16. 2017 High

    Defined a tumor-microenvironment mechanism: NCKIPSD loss in fibroblasts recruits mDia2/APC to microtubules, raising microtubule acetylation and YAP nuclear translocation to drive CAF activation and tumor progression.

    Evidence Knockout MEFs, microtubule acetylation and recruitment assays, YAP imaging, marker qPCR, orthotopic breast cancer model

    PMID:28652253

    Open questions at the time
    • How NCKIPSD normally restrains mDia2/APC microtubule recruitment unknown
    • Direct molecular link between acetylation and YAP nuclear entry not resolved
  17. 2019 High

    Resolved the molecular logic of NCKIPSD-driven Rab5 activation: ERK phosphorylation at Thr-242 lets NCKIPSD bridge Gapex5 (SH3) to inactive Rab5/GDI2 (C-terminus) on endosomes.

    Evidence Co-IP, Thr-242 mutation, domain mapping, EGF stimulation, and Rab5 activation assays

    PMID:31358736

    Open questions at the time
    • Whether the same phospho-event coordinates other endocytic partners unaddressed
    • Kinetic ordering relative to dynamin/syndapin steps unknown
  18. 2019 High

    Showed NCKIPSD loss remodels the ECM, upregulating FN+EDA that signals through integrin alpha4beta1 to enhance breast cancer aggressiveness, a druggable axis.

    Evidence Knockout MEFs, FN+EDA Western/IF, integrin co-IP, co-culture invasion assays, orthotopic model, irigenin inhibition

    PMID:31637720

    Open questions at the time
    • Mechanism by which NCKIPSD restrains FN+EDA expression not defined
    • Cytoskeletal versus transcriptional contribution to ECM phenotype unseparated
  19. 2020 High

    Reconceived NCKIPSD's actin function: rather than only promoting branching, it nucleates unbranched filaments via Arp2/3 and forms a ternary SPIN90-Arp2/3-mDia1 complex that produces long formin-elongated filaments, shifting cortex architecture.

    Evidence In vitro reconstitution, single-molecule TIRF microscopy, ternary complex assays, and cell cortex network analysis

    PMID:32572169

    Open questions at the time
    • How this ternary-complex pathway is regulated by the upstream signaling/phospho-switches not connected
    • Relative in vivo prevalence versus N-WASP-branched nucleation unresolved
  20. 2022 Medium

    Identified an upstream regulatory layer: cancer-cell-derived exosomal miR-130b-3p downregulates NCKIPSD in fibroblasts to drive CAF differentiation.

    Evidence miR-130b-3p ectopic expression, exosome delivery, fibroblast differentiation and cancer motility assays, patient tissue correlation

    PMID:35948548

    Open questions at the time
    • Direct 3'UTR binding not detailed in this evidence
    • Whether miRNA-driven NCKIPSD loss recapitulates the full mDia2/YAP and FN+EDA phenotypes untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How NCKIPSD's signal-driven phospho-switches integrate its competing actin-nucleating, formin-recruiting, and cofilin-sequestering activities at a single subcellular location remains unresolved.
  • No structural model of the autonomous Arp2/3-activating C-terminus
  • No unified model reconciling Cdc42-independent Arp2/3 activation with the observed Cdc42 and Rho regulation
  • Mechanism of the MLL-AF3p21 fusion in leukemogenesis uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 6 GO:0098772 molecular function regulator activity 5 GO:0008092 cytoskeletal protein binding 3
Localization
GO:0005856 cytoskeleton 4 GO:0005768 endosome 3 GO:0005829 cytosol 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-112316 Neuronal System 4 R-HSA-162582 Signal Transduction 4 R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-1474244 Extracellular matrix organization 1
Partners
ARPCBAIAP2DIAPH1DLG4DNM1NCK1SHANKWASL
Complex memberships
SPIN90-Arp2/3-mDia1 ternary complexbetaPIX-WASP-SPIN90-Nck complexpostsynaptic density (PSD-95/Shank)

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 WISH/NCKIPSD binds N-WASP through its SH3 domain and Ash/Grb2 through proline-rich regions, and strongly enhances N-WASP-induced Arp2/3 complex activation independent of Cdc42 in vitro, leading to rapid actin polymerization. Coexpression of WISH and N-WASP induced microspike formation even with a Cdc42-binding-deficient N-WASP mutant (H208D). WISH also activated actin polymerization in N-WASP-depleted brain extracts, indicating both N-WASP-dependent and -independent pathways to Arp2/3 activation. In vitro Arp2/3 actin polymerization assay, co-immunoprecipitation, N-WASP depletion from brain extracts, cell overexpression, domain-binding assays The Journal of cell biology High 11157975
2001 SPIN90/NCKIPSD was identified as an Nck-binding protein via yeast two-hybrid screening; it binds the first and third SH3 domains of Nck in vitro. SPIN90 contains an SH3 domain, proline-rich motifs, a serine/threonine-rich region, and a C-terminal hydrophobic region. It is colocalized with Nck at sarcomere Z-discs in cardiac myocytes, and antisera against SPIN90 disrupts sarcomere structure. Yeast two-hybrid, in vitro binding assay, immunofluorescence colocalization, antibody microinjection phenotype The Journal of biological chemistry High 11278500
2000 AF3p21/NCKIPSD was identified as a novel MLL fusion partner in therapy-related leukemia with t(3;11)(p21;q23). The AF3p21 protein (722 aa) contains an SH3 domain, proline-rich domain, and bipartite nuclear localization signal (NLS). In the MLL-AF3p21 fusion, exon 6 of MLL fuses to exon 2 of AF3p21, producing a chimeric protein with MLL AT-hooks and AF3p21 proline-rich domain and NLS but lacking the AF3p21 SH3 domain. Genomic DNA library screening, RNA analysis, sequencing of fusion junction Blood Medium 10648423
2001 AF3p21/NCKIPSD has a homo-oligomerization domain demonstrated by mammalian two-hybrid system, making it structurally analogous to MLL fusion partners AF10 and AF17. Mammalian two-hybrid system Leukemia & lymphoma Low 11697487
2003 SPIN90/NCKIPSD phosphorylation is regulated by ERK1 (activated by cell adhesion and PDGF) and modulates interaction with Nck. SPIN90 binds betaPIX, WASP, and ERK1 as identified by in vitro binding and yeast two-hybrid. The betaPIX.WASP.SPIN90 complex interacts with Nck in a cell adhesion-dependent manner (abolished in suspended or cytochalasin D-treated cells, restored on fibronectin); SPIN90 phosphorylation by ERK promotes this complex–Nck interaction. Yeast two-hybrid, in vitro binding assays, co-immunoprecipitation, cell adhesion manipulation, ERK kinase assay, overexpression of SH3/PRD domain constructs The Journal of biological chemistry High 14559906
2005 SPIN90/NCKIPSD redistributes to the cell cortex and promotes lamellipodia/membrane ruffle formation in response to PDGF in COS-7 cells; knockdown abolishes this redistribution. The C-terminus of SPIN90 binds both the Arp2/3 complex and G-actin in vitro, and this binding activates Arp2/3 to drive actin polymerization. When coexpressed with PI4P5-kinase, SPIN90 localizes to actin comet tails. siRNA knockdown, PDGF stimulation assay, in vitro Arp2/3 activation assay (C-terminal domain binding), actin comet tail coexpression assay The Journal of biological chemistry High 16253999
2005 SPIN90/NCKIPSD binds dynamin I in presynaptic compartments through SH3-PRD interaction (pull-down and co-immunoprecipitation), and participates in synaptic vesicle endocytosis. Both overexpression and siRNA knockdown of SPIN90 impaired synaptic vesicle endocytosis, and endocytic defects from overexpression were rescued by abolishing SPIN90–dynamin I interaction. Exocytosis kinetics were unaffected. Pull-down, co-immunoprecipitation, siRNA knockdown, overexpression, FM dye-based synaptic vesicle endocytosis assay, rescue experiments The Journal of neuroscience High 16221862
2006 SPIN90/NCKIPSD binds the SH3 domain of syndapin via its proline-rich domain (in vitro and in vivo) and also associates with clathrin. Overexpression of SPIN90 or its PRD domain (syndapin-binding domain) inhibited transferrin uptake (clathrin-mediated endocytosis), and this inhibition was reversed by co-expression of syndapin. SPIN90 knockdown (antibody microinjection or siRNA) also inhibited transferrin internalization. SPIN90 co-localizes with EEA1/Rab5 early endosomes and travels with moving vesicles in live cells. Yeast two-hybrid, in vitro pull-down, co-immunoprecipitation, transferrin uptake assay, siRNA knockdown, antibody microinjection, live-cell time-lapse imaging Genes to cells High 16999739
2006 SPIN90/NCKIPSD localizes to dendritic spines where it associates with PSD-95. Overexpression increased dendritic filopodia/spine number and length via an N-WASP-independent mechanism; siRNA knockdown reduced spine density. PSD-95-induced spinogenesis was abolished by SPIN90 knockdown. In response to chemically induced LTP, SPIN90 redistributed to dendritic spines in association with PSD-95. Co-immunoprecipitation (SPIN90 with PSD-95), siRNA knockdown, overexpression, chemical LTP induction, immunofluorescence localization in neurons The EMBO journal High 16990791
2007 The SH3 domains of SPIN90/NCKIPSD and Src directly bind palladin's poly-proline sequence (in vitro). SPIN90–palladin interaction controls intracellular targeting of SPIN90. Palladin and SPIN90 co-localize in PDGF-induced membrane ruffles/lamellipodia. Knockdown of SPIN90 did not inhibit Src-induced cytoskeletal rearrangement, whereas palladin knockdown caused cytoskeletal disorganization and inhibited remodeling. Palladin is tyrosine phosphorylated by active Src. In vitro binding (direct SH3-polyproline), co-immunoprecipitation, siRNA knockdown, active Src overexpression, immunofluorescence colocalization Experimental cell research High 17537434
2009 SPIN90/NCKIPSD is a novel binding partner for Shank proteins in the PSD (co-immunoprecipitation from brain lysates). SPIN90 and Shank co-localize in postsynaptic dendrites and synergistically mediate spine maturation and spine head enlargement. SPIN90 overexpression causes accumulation of Shank and PSD-95 in dendritic spines. In SPIN90 knockout mice, PSD protein composition is altered and actin cytoskeleton in hippocampal neurons is abnormal. Co-immunoprecipitation from brain lysates, overexpression, SPIN90 knockout mice, immunofluorescence Journal of neurochemistry High 19302483
2009 SPIN90/NCKIPSD forms a complex with IRSp53 mediated through direct association of SPIN90's PRD with the SH3 domain of IRSp53 (in vivo co-immunoprecipitation). SPIN90 and IRSp53 cooperate to mediate Rac activation, co-localizing at leading edges in PDGF-treated cells. SPIN90 siRNA knockdown reduced lamellipodia and IRSp53 localization at protrusions. Competitive inhibition of SPIN90–IRSp53 binding via SPIN90 PRD dramatically reduced ruffle formation. Co-immunoprecipitation, siRNA knockdown, domain competitive inhibition, immunofluorescence colocalization, PDGF stimulation Experimental cell research High 19460367
2009 In DIP/WISH (NCKIPSD)-deficient mouse embryonic fibroblasts, Rho activity is constitutively elevated, cell motility and adhesion are impaired, and cells display many stress fibers due to clustering of pre-existing actin filaments. DIP/WISH thus functions as a negative regulator of Rho and modulates cell adhesion by controlling integration of adhesion molecules. Knockout mouse-derived MEFs, Rho activity assay, cell motility assay, immunofluorescence for stress fibers/adhesion Genes to cells High 19778379
2011 SPIN90/NCKIPSD is enriched in growth cones and neuronal shafts in young hippocampal neurons, with localization dependent on F-actin. SPIN90 knockout reduces growth cone area, filopodial number, total neurite length, and Cdc42 activity compared to wild-type neurons. SPIN90 knockout neurons, immunocytochemistry, F-actin co-localization, growth cone morphometry, Cdc42 activity assay Experimental cell research High 21763308
2013 SPIN90/NCKIPSD is tyrosine phosphorylated by Src kinase (in vitro and in vivo kinase assays). Phospho-SPIN90 is targeted to dendritic spines in hippocampal neurons. A phospho-deficient mutant fails to accumulate at spines or bind PSD-95/Shank efficiently; phospho-mimicking mutant localizes to spines and binds PSD-95/Shank with increased efficiency. Neurons overexpressing SPIN90 WT or phospho-mimicking mutant display enlarged spine heads and enhanced postsynaptic function (increased EPSC amplitude and frequency). In vitro kinase assay, in vivo kinase assay, phospho-deficient/mimetic mutants, immunofluorescence localization, electrophysiology (EPSC recording) PloS one High 23342115
2013 SPIN90/NCKIPSD knockdown attenuates EGFR endocytosis: knockdown cells have higher surface EGFR, fewer EGFR-containing endosomes, smaller endosome size, and delayed early endosomal targeting. Domain overexpression (SH3, PRD, CC domains) causes aberrant Rab5-positive endosome morphology and defective endosomal movement. SPIN90 knockdown-enhanced EGFR stability leads to elevated ERK1/2 activation and increased cyclin D1-dependent cell proliferation. Stable siRNA knockdown, electron microscopy of EGFR distribution, fluorescent confocal microscopy of endosomes, surface EGFR quantification, domain overexpression, cell proliferation assay, ERK1/2 activation assay PloS one High 24340049
2013 SPIN90/NCKIPSD is dephosphorylated by STEP61 (striatal-enriched protein tyrosine phosphatase) upon NMDA stimulation and translocates from dendritic spines to dendritic shafts. Phosphorylated SPIN90 binds cofilin and inhibits its actin-severing activity; dephosphorylation releases cofilin for actin depolymerization. A phosphomimetic mutant (SPIN90 YE) remained in spines after NMDAR activation, bound cofilin, and prevented actin depolymerization, cortactin/drebrin redistribution, and spine shrinkage. NMDA stimulation of neurons, phosphatase identification (STEP61), co-immunoprecipitation of phospho-SPIN90 with cofilin, phosphomimetic/phospho-deficient mutants, immunofluorescence of spine morphology, cortactin/drebrin redistribution assays Cellular and molecular life sciences High 23765104
2017 SPIN90/NCKIPSD depletion in stromal fibroblasts facilitates recruitment of mDia2 and APC complex to microtubules, resulting in increased microtubule acetylation. This promotes nuclear localization of YAP, which upregulates myofibroblast marker gene expression on soft matrices, driving cancer-associated fibroblast (CAF) activation. In vivo, Spin90 deficiency enhanced tumor progression, and blockade of microtubule acetylation in CAF inhibited tumor growth in mice. Spin90 knockout mouse-derived fibroblasts, microtubule acetylation assay, mDia2/APC co-immunoprecipitation/recruitment assay, YAP nuclear localization by imaging, myofibroblast marker qPCR, orthotopic breast cancer mouse model Cancer research High 28652253
2019 SPIN90/NCKIPSD acts as an adaptor that facilitates Rab5 activation during EGF-mediated endocytosis. SPIN90 binds inactive Rab5/GDI2 complex through its C-terminus. ERK-mediated phosphorylation of SPIN90 at Thr-242 in response to EGF signaling enables SPIN90 to bind the GEF Gapex5 through its N-terminal SH3 domain, mediating Gapex5–Rab5 proximity and Rab5 activation on endosomal membranes. Co-immunoprecipitation, phosphorylation-site mutation (Thr-242), domain mapping, EGF stimulation, Rab5 activation assay, endosomal localization Experimental & molecular medicine High 31358736
2019 In Spin90-knockout MEFs, extra domain A-containing fibronectin (FN+EDA) is upregulated, promotes fibril formation in ECM, and specifically interacts with integrin α4β1. FN+EDA from Spin90-KO MEFs increases breast cancer cell proliferation, migration, and invasion. Irigenin, which blocks integrin α4β1–FN+EDA interaction, inhibited fibril formation by KO MEFs and reduced tumor growth and lung metastases in orthotopic mouse models. Spin90-knockout MEFs, FN+EDA Western blot/IF, integrin co-immunoprecipitation, breast cancer cell co-culture proliferation/migration/invasion assays, orthotopic mouse model, pharmacological inhibition with irigenin Journal of cellular physiology High 31637720
2020 In vitro, SPIN90/NCKIPSD promotes formation of unbranched actin filaments by Arp2/3. In cells, SPIN90 favors a formin-dominated cortex. Two mechanisms account for this: (1) efficient recruitment of mDia1 to SPIN90-Arp2/3 nucleated filaments, and (2) formation of a ternary SPIN90-Arp2/3-mDia1 complex that greatly enhances filament nucleation. Both mechanisms yield rapidly elongating filaments with mDia1 at barbed ends and SPIN90-Arp2/3 at pointed ends. In networks, SPIN90 lowers branching density and increases the proportion of long mDia1-elongated filaments. In vitro actin polymerization reconstitution, TIRF microscopy of single filaments, ternary complex formation assay, cell cortex analysis Nature cell biology High 32572169
2022 miR-130b-3p directly downregulates SPIN90/NCKIPSD in stromal fibroblasts. Ectopic expression of miR-130b-3p in fibroblasts accelerated their differentiation to CAFs and promoted cancer cell motility, associated with SPIN90 downregulation. miR-130b-3p is generated in luminal A-type cancer cells and delivered to fibroblasts via exosomes. miRNA target validation (ectopic expression, luciferase reporter implied), fibroblast differentiation assay, exosome delivery assay, cancer cell motility assay, patient tissue correlation Oncogenesis Medium 35948548

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Maternal age and chromosomally abnormal pregnancies: what we know and what we wish we knew. Current opinion in pediatrics 167 19881348
2011 Titanium dioxide nanoparticles induced cytotoxicity, oxidative stress and DNA damage in human amnion epithelial (WISH) cells. Toxicology in vitro : an international journal published in association with BIBRA 163 22210200
2001 A novel neural Wiskott-Aldrich syndrome protein (N-WASP) binding protein, WISH, induces Arp2/3 complex activation independent of Cdc42. The Journal of cell biology 127 11157975
2012 What lies behind the wish to hasten death? A systematic review and meta-ethnography from the perspective of patients. PloS one 114 22606338
1984 Receptors for human gamma interferon: binding and crosslinking of 125I-labeled recombinant human gamma interferon to receptors on WISH cells. Proceedings of the National Academy of Sciences of the United States of America 107 6089181
2018 The Alphavirus Exit Pathway: What We Know and What We Wish We Knew. Viruses 81 29470397
2010 The wish to hasten death: a review of clinical studies. Psycho-oncology 72 20821377
2005 Modulation of cytokine-induced cyclooxygenase 2 expression by PPARG ligands through NFkappaB signal disruption in human WISH and amnion cells. Biology of reproduction 72 15843495
1997 Rapid and transient induction of cyclo-oxygenase 2 by epidermal growth factor in human amnion-derived WISH cells. The Biochemical journal 61 9032453
2003 Sphingosine 1-phosphate in amniotic fluid modulates cyclooxygenase-2 expression in human amnion-derived WISH cells. The Journal of biological chemistry 60 12796504
1994 Interleukin-1 beta regulates the inducible cyclooxygenase in amnion-derived WISH cells. Prostaglandins 58 7892511
1998 Involvement of phosphatidate phosphohydrolase in arachidonic acid mobilization in human amnionic WISH cells. The Journal of biological chemistry 57 9516474
2013 Patient education in allogeneic hematopoietic cell transplant: what patients wish they had known about quality of life. Bone marrow transplantation 56 24121210
2000 Fetal membrane distention: I. Differentially expressed genes regulated by acute distention in amniotic epithelial (WISH) cells. American journal of obstetrics and gynecology 54 10649156
2000 WISH-PC2: a unique xenograft model of human prostatic small cell carcinoma. Cancer research 49 11118033
1996 Induction of both cytosolic phospholipase A2 and prostaglandin H synthase-2 by interleukin-1 beta in WISH cells in inhibited by dexamethasone. Prostaglandins 49 8711133
2017 WISH, a novel CFEM GPCR is indispensable for surface sensing, asexual and pathogenic differentiation in rice blast fungus. Fungal genetics and biology : FG & B 48 28576657
2020 SPIN90 associates with mDia1 and the Arp2/3 complex to regulate cortical actin organization. Nature cell biology 46 32572169
2001 SPIN90 (SH3 protein interacting with Nck, 90 kDa), an adaptor protein that is developmentally regulated during cardiac myocyte differentiation. The Journal of biological chemistry 45 11278500
2005 Interaction of SPIN90 with the Arp2/3 complex mediates lamellipodia and actin comet tail formation. The Journal of biological chemistry 42 16253999
2013 White fish reduces cardiovascular risk factors in patients with metabolic syndrome: the WISH-CARE study, a multicenter randomized clinical trial. Nutrition, metabolism, and cardiovascular diseases : NMCD 39 24462043
2007 Palladin interacts with SH3 domains of SPIN90 and Src and is required for Src-induced cytoskeletal remodeling. Experimental cell research 39 17537434
2013 Zinc ferrite nanoparticles activate IL-1b, NFKB1, CCL21 and NOS2 signaling to induce mitochondrial dependent intrinsic apoptotic pathway in WISH cells. Toxicology and applied pharmacology 36 24035972
2004 Neurotoxic prostaglandin J2 enhances cyclooxygenase-2 expression in neuronal cells through the p38MAPK pathway: a death wish? Journal of neuroscience research 36 15523637
1995 Interleukin-1 beta induces the synthesis and activity of cytosolic phospholipase A2 and the release of prostaglandin E2 in human amnion-derived WISH cells. Prostaglandins 36 7480804
2002 Shiga toxin 1 and 2 induce apoptosis in the amniotic cell line WISH. Journal of the Society for Gynecologic Investigation 33 11839504
2005 Nanomolar and micromolar effects of 15-deoxy-delta 12,14-prostaglandin J2 on amnion-derived WISH epithelial cells: differential roles of peroxisome proliferator-activated receptors gamma and delta and nuclear factor kappa B. Molecular pharmacology 32 15821150
2000 Novel SH3 protein encoded by the AF3p21 gene is fused to the mixed lineage leukemia protein in a therapy-related leukemia with t(3;11) (p21;q23). Blood 32 10648423
1997 CA125 phosphorylation is associated with its secretion from the WISH human amnion cell line. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 32 9276028
2006 SPIN90/WISH interacts with PSD-95 and regulates dendritic spinogenesis via an N-WASP-independent mechanism. The EMBO journal 31 16990791
2003 Expression of aquaporin 8 and its up-regulation by cyclic adenosine monophosphate in human WISH cells. American journal of obstetrics and gynecology 31 12712100
2014 Do participants in genome sequencing studies of psychiatric disorders wish to be informed of their results? A survey study. PloS one 30 24983240
2012 Cytotoxic and necrotic responses in human amniotic epithelial (WISH) cells exposed to organophosphate insecticide phorate. Mutation research 29 22306305
1999 Regulation of cyclooxygenase-2 expression by phosphatidate phosphohydrolase in human amnionic WISH cells. The Journal of biological chemistry 28 10488110
1998 Tumour necrosis factor-alpha stimulates increased expression of prostaglandin endoperoxide H synthase Type 2 mRNA in amnion-derived WISH cells. Journal of molecular endocrinology 27 9584837
2003 Regulation of SPIN90 phosphorylation and interaction with Nck by ERK and cell adhesion. The Journal of biological chemistry 26 14559906
2001 15-deoxy-delta12,14-prostaglandin J2-induced apoptosis in amnion-like WISH cells. Prostaglandins & other lipid mediators 26 11785780
1988 Characterization of prostaglandin production in amnion-derived WISH cells. American journal of obstetrics and gynecology 26 3207114
2020 Small molecule ERK5 kinase inhibitors paradoxically activate ERK5 signalling: be careful what you wish for…. Biochemical Society transactions 25 32915196
2014 Weighted Interaction SNP Hub (WISH) network method for building genetic networks for complex diseases and traits using whole genome genotype data. BMC systems biology 25 25032480
2006 Interaction of SPIN90 with syndapin is implicated in clathrin-mediated endocytic pathway in fibroblasts. Genes to cells : devoted to molecular & cellular mechanisms 25 16999739
1997 The effect of interleukin-1 beta and interleukin-4 on the expression of prostaglandin receptors EP1 and EP3 in amnion WISH cells. American journal of reproductive immunology (New York, N.Y. : 1989) 25 9352015
1988 Light-stimulated ultraweak photon reemission of human amnion cells and Wish cells. Cell biophysics 25 2456152
2017 SPIN90 Depletion and Microtubule Acetylation Mediate Stromal Fibroblast Activation in Breast Cancer Progression. Cancer research 24 28652253
2005 Interaction of SPIN90 with dynamin I and its participation in synaptic vesicle endocytosis. The Journal of neuroscience : the official journal of the Society for Neuroscience 24 16221862
2016 The wish to die among palliative home care clients in Ontario, Canada: A cross-sectional study. BMC palliative care 23 26924601
1997 Interleukin-8 selectively enhances cytopathic effect (CPE) induced by positive-strand RNA viruses in the human WISH cell line. Biochemical and biophysical research communications 23 9207237
2015 Fluorescent whole-mount RNA in situ hybridization (F-WISH) in plant germ cells and the fertilized ovule. Methods (San Diego, Calif.) 22 26521978
2010 Whole-genome in-silico subtractive hybridization (WISH)--using massive sequencing for the identification of unique and repetitive sex-specific sequences: the example of Schistosoma mansoni. BMC genomics 22 20565937
1994 Epidermal growth factor enhances secretion of the ovarian tumor-associated cancer antigen CA125 from the human amnion WISH cell line. Journal of the Society for Gynecologic Investigation 22 9419754
1993 Characterization of CA 125 synthesized by the human epithelial amnion WISH cell line. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 22 8235310
1997 Acanthamoeba castellanii metabolites increase the intracellular calcium level and cause cytotoxicity in wish cells. Microbial pathogenesis 20 9245619
1996 Stimulation of prostaglandin E2 synthesis by interleukin-1beta is amplified by interferons but inhibited by interleukin-4 in human amnion-derived WISH cells. Biochimica et biophysica acta 20 9244174
2001 By releasing ADP, Acanthamoeba castellanii causes an increase in the cytosolic free calcium concentration and apoptosis in wish cells. Infection and immunity 18 11349088
1997 Hypotonic stress increases cyclooxygenase-2 expression and prostaglandin release from amnion-derived WISH cells. The Journal of biological chemistry 18 9242685
1989 Phorbol ester and interferon-gamma modulation of epidermal growth factor receptors on human amniotic (WISH) cells. The Journal of biological chemistry 18 2495278
1985 The wish to have a child. A pilot-study of infertile couples. Acta psychiatrica Scandinavica 18 4091031
2009 Regulation of dendritic spine morphology by SPIN90, a novel Shank binding partner. Journal of neurochemistry 17 19302483
2006 Liposome-mediated IL-28 and IL-29 expression in A549 cells and anti-viral effect of IL-28 and IL-29 on WISH cells. Acta pharmacologica Sinica 17 16539846
1992 Catecholamines modulate epidermal growth factor-induced prostaglandin E2 production in amnion-like (WISH) cells by means of a cyclic adenosine monophosphate-dependent pathway. American journal of obstetrics and gynecology 17 1370742
2003 17Beta-eEstradiol stimulates arachidonate release from human amnion-like WISH cells through a rapid mechanism involving a membrane receptor. Endocrinology 16 12865314
2019 Extra domain A-containing fibronectin expression in Spin90-deficient fibroblasts mediates cancer-stroma interaction and promotes breast cancer progression. Journal of cellular physiology 15 31637720
2018 WISH-R- a fast and efficient tool for construction of epistatic networks for complex traits and diseases. BMC bioinformatics 15 30064383
2013 SPIN90 phosphorylation modulates spine structure and synaptic function. PloS one 15 23342115
2012 WISH cell line: from the antiviral system to a novel reporter gene assay to test the potency of human IFN-α and IFN-β. Journal of immunological methods 15 22549076
2002 Regulation of cyclooxygenase-2 expression by phospholipase D in human amnion-derived WISH cells. Molecular pharmacology 15 11854442
1998 Tumor necrosis factor-alpha upregulates the prostaglandin E2 EP1 receptor subtype and the cyclooxygenase-2 isoform in cultured amnion WISH cells. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 15 9877447
2022 Tumor-derived miR-130b-3p induces cancer-associated fibroblast activation by targeting SPIN90 in luminal A breast cancer. Oncogenesis 14 35948548
2005 Novel targeting of cyclooxygenase-2 (COX-2) pre-mRNA using antisense morpholino oligonucleotides directed to the 3' acceptor and 5' donor splice sites of exon 4: suppression of COX-2 activity in human amnion-derived WISH and myometrial cells. Molecular pharmacology 14 16354766
2001 Structure of AF3p21, a new member of mixed lineage leukemia (MLL) fusion partner proteins-implication for MLL-induced leukemogenesis. Leukemia & lymphoma 14 11697487
1999 Interleukin-4 differentially regulates prostaglandin production in amnion-derived WISH cells stimulated with pro-inflammatory cytokines and epidermal growth factor. Prostaglandins, leukotrienes, and essential fatty acids 14 10397407
1997 Induction of prostaglandin H synthase-2 and tumor necrosis factor-alpha in human amnionic WISH cells by various stimuli occurs through distinct intracellular mechanisms. The Journal of pharmacology and experimental therapeutics 14 9023325
1989 The in vitro antiviral activity of tumor necrosis factor (TNF) in WISH cells is mediated by IFN-beta induction. Antiviral research 14 2543288
1989 Comparative study on the antiviral activity of tumor necrosis factor (TNF)-alpha, lymphotoxin/TNF-beta, and IL-1 in WISH cells. Immunology letters 14 2548953
2021 "I wish that there was more info": characterizing the uncertainty experienced by carriers of pathogenic ATM and/or CHEK2 variants. Familial cancer 13 33855648
2013 SPIN90 knockdown attenuates the formation and movement of endosomal vesicles in the early stages of epidermal growth factor receptor endocytosis. PloS one 13 24340049
2004 Hydrogen peroxide induced apoptosis in amnion-derived WISH cells is not inhibited by vitamin C. Placenta 13 15028418
2004 Stimulation of early gene induction and cell proliferation by lysophosphatidic acid in human amnion-derived WISH cells: role of phospholipase D-mediated pathway. Biochemical pharmacology 13 15194005
1998 Making informed choices: medium, serum, and serum-free medium. How to choose the appropriate medium and culture system for the model you wish to create. Methods in cell biology 13 9648097
1998 Effects of interleukin-4 on the expression and activity of prostaglandin endoperoxide H synthase-2 in amnion-derived WISH cells. Journal of molecular endocrinology 13 9845672
1983 The HLA proteins and a related protein of 28 kDa are preferentially induced by interferon-gamma in human WISH cells. European journal of immunology 13 6416868
2009 SPIN90-IRSp53 complex participates in Rac-induced membrane ruffling. Experimental cell research 12 19460367
2001 Phthalic acid mimics 17beta-estradiol actions in WISH cells. Toxicology letters 12 11137322
2019 SPIN90, an adaptor protein, alters the proximity between Rab5 and Gapex5 and facilitates Rab5 activation during EGF endocytosis. Experimental & molecular medicine 11 31358736
2013 SPIN90 dephosphorylation is required for cofilin-mediated actin depolymerization in NMDA-stimulated hippocampal neurons. Cellular and molecular life sciences : CMLS 11 23765104
2009 Fluorescence-activated cell sorting (FACS) of whole mount in situ hybridization (WISH) labelled haematopoietic cell populations in the zebrafish. British journal of haematology 11 19133983
2000 Corticotropin-releasing hormone increases the expression of the prostaglandin E(2) receptor subtype EP1 in amnion WISH cells. Biology of reproduction 11 10611063
1999 Cyclooxygenase inhibitors decrease apoptosis initiated by actinomycin D, cycloheximide, and staurosporine in amnion-derived WISH cells. Journal of the Society for Gynecologic Investigation 11 10554762
2020 IL-6 but Not TNFα Levels Are Associated With Time to Pregnancy in Female Rheumatoid Arthritis Patients With a Wish to Conceive. Frontiers in pharmacology 10 33362560
2009 DIP/WISH-deficient mice reveal Dia- and N-WASP-interacting protein as a regulator of cytoskeletal dynamics in embryonic fibroblasts. Genes to cells : devoted to molecular & cellular mechanisms 10 19778379
2000 Subcellular localization and PKC-dependent regulation of the human lysophospholipase A/acyl-protein thioesterase in WISH cells. Biochimica et biophysica acta 10 10760470
2003 WISH cells as a model for the "in vitro" study of amnion pathophysiology. Current drug targets. Immune, endocrine and metabolic disorders 9 12570726
2002 Lactosylceramide-induced apoptosis in primary amnion cells and amnion-derived WISH cells. Journal of the Society for Gynecologic Investigation 9 12383912
2001 17beta-estradiol modulates prostaglandin E2 release from human amnion-derived wish cells. Biology of reproduction 9 11369594
2001 Diagnostics and treatment of HIV-discordant couples who wish to have children. European journal of medical research 9 11496900
1998 Comparative studies on the effects of interleukin-4 and interleukin-13 on cytokine and prostaglandin E2 production by amnion-derived WISH cells. American journal of reproductive immunology (New York, N.Y. : 1989) 9 9870076
1989 Enhancement of interferon-induced 2-5 oligoadenylate synthetase activity by retinoic acid in human histiocytic lymphoma U937 cells and WISH cells. Differentiation; research in biological diversity 9 2472992
2011 Control of growth cone motility and neurite outgrowth by SPIN90. Experimental cell research 8 21763308
2005 Despite transcriptional and functional coordination, cyclooxygenase-2 and microsomal prostaglandin E synthase-1 largely reside in distinct lipid microdomains in WISH epithelial cells. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 8 15983118
2000 Anticancer drug action on poly(A) polymerase activity and isoforms during HeLa and WISH cell apoptosis. The International journal of biological markers 8 10883892

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