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Showing TRIP10 — CIP4 is a alias.

TRIP10

Cdc42-interacting protein 4 · UniProt Q15642

Length
601 aa
Mass
68.4 kDa
Annotated
2026-06-10
34 papers in source corpus 27 papers cited in narrative 27 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

TRIP10/CIP4 is an F-BAR domain scaffold that couples membrane curvature sensing and generation to actin remodeling, acting as a downstream effector of GTP-loaded Cdc42-family GTPases to drive endocytosis, cell migration, and membrane morphogenesis (PMID:18976911, PMID:19920150, PMID:30061681). Its curved phosphoinositide-binding F-BAR face targets it to deformed and curved membranes, where it self-assembles via intrinsically disordered regions and recruits actin-regulatory machinery—N-WASp/WASP, WAVE/SCAR, and Dynamin—to invaginating membranes to promote vesicle invagination and scission (PMID:19716703, PMID:19632321, PMID:37528083). Through this curvature-to-actin coupling CIP4 supports multiple endocytic modes: it is required for the EEA1-to-lysosome transit of EGFR and thereby limits sustained ERK signaling (PMID:19632321), promotes insulin- and TC10/Cdc42-dependent GLUT4 endocytosis through N-WASp and Dynamin-2 (PMID:12242347, PMID:19509061), and primes the plasma membrane for fast endophilin-mediated endocytosis by recruiting SHIP2 and lamellipodin to generate local PI(3,4)P2 (PMID:30061681). CIP4-null mice show delayed, reduced endocytosis of multiple cargoes in vivo, confirming a broad endocytic role (PMID:19920150). CIP4 also localizes to protruding membrane edges in a PIP3- and actin architecture-dependent manner and acts through Rac1/WAVE1 to control lamellipodial dynamics, neurite initiation, and directional chemotaxis (PMID:22361215, PMID:23572514, PMID:23644527). Physiologically, CIP4 is required for integrin-dependent T-cell trafficking and germinal center responses (PMID:20805498), for proplatelet formation in megakaryocytes via control of membrane deformability and cortical actin tension (PMID:23881916), and for radial migration of cortical neurons (PMID:40721321). PKA phosphorylation at T225 enhances CIP4 binding to CDC42 and its localization to invadopodia, promoting cancer cell invasion and metastasis through CDC42 recruitment and NF-κB activation (PMID:31319138, PMID:35317515), while AKAP350-mediated centrosomal recruitment coordinates nucleus-centrosome-Golgi axis formation and migration directionality (PMID:26208639).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2002 Medium

    Established CIP4 as a Cdc42-family GTPase effector linked to a defined physiological output, answering whether CIP4 transduces GTPase signals to membrane traffic.

    Evidence Constitutively active/dominant-negative TC10 constructs and TC10-binding mutants with GLUT4 translocation readout in 3T3L1 adipocytes

    PMID:12242347

    Open questions at the time
    • Did not resolve the actin/dynamin machinery downstream of CIP4
    • Single cell type, overexpression-based
  2. 2006 Medium

    Placed CIP4 in a physical complex with the formin DAAM1, RhoA/Cdc42 and Src, beginning to define how CIP4 couples GTPase activity to actin dynamics.

    Evidence Yeast two-hybrid, co-IP and GTP-dependent pulldown with morphological readout

    PMID:16630611

    Open questions at the time
    • No interface mapping or reconstitution
    • Functional consequence of the DAAM1 interaction not dissected
  3. 2008 High

    Defined the core CIP4 effector mechanism: it links Cdc42 to WASp/Arp2/3 and Dynamin to drive cargo-specific (E-cadherin) endocytosis, establishing the curvature-actin-scission module in vivo.

    Evidence Drosophila genetic loss-of-function, epistasis with dynamin mutants, co-IP and live imaging

    PMID:18976911

    Open questions at the time
    • Whether the module generalizes to other cargoes left open at the time
    • Did not address WAVE involvement
  4. 2009 High

    Extended the effector module to both WASP and WAVE recruitment and clarified the division of labor (WAVE for actin-comet motility), and demonstrated CIP4 controls EGFR endosomal transit to limit ERK signaling and GLUT4 endocytosis through N-WASp/Dynamin-2.

    Evidence Drosophila genetic rescue and live imaging; siRNA, endogenous co-IP, FRET, surface GLUT4 flow cytometry; F-BAR mutagenesis with endosomal markers and ERK assays

    PMID:19509061 PMID:19632321 PMID:19716703

    Open questions at the time
    • Quantitative contribution of WASP vs WAVE to mammalian endocytosis unresolved
    • Structural basis of F-BAR membrane targeting not yet visualized
  5. 2009 High

    Provided in vivo genetic proof that CIP4 affects multiple modes of endocytosis and modulates whole-animal insulin sensitivity, moving beyond single-cell overexpression.

    Evidence Constitutive CIP4-knockout mouse with transferrin/dextran/HRP uptake and 2-deoxyglucose/membrane fractionation assays

    PMID:19920150

    Open questions at the time
    • Did not identify which curvature-generating step is rate-limiting
    • Tissue-specific contributions not separated
  6. 2010 High

    Demonstrated organism-level requirements for CIP4 in integrin-dependent T-cell trafficking and immunity, and identified curvature-dependent membrane tubulation as a mechanism controlling receptor (PDGFRβ) internalization and migration.

    Evidence CIP4-null mice with adhesion/transmigration/contact-hypersensitivity assays; siRNA with tubulation, dorsal ruffle and PDGFRβ internalization readouts

    PMID:19909236 PMID:20805498

    Open questions at the time
    • Molecular link between membrane tubulation and integrin signaling not detailed
    • Redundancy with FBP17/Toca-1 only partly addressed
  7. 2010 Medium

    Showed TRIP10 expression is epigenetically controlled and that this regulation influences mesenchymal stem cell lineage choice, indicating transcriptional control of the locus has developmental consequences.

    Evidence Targeted promoter methylation with EGFP reporter, bisulfite sequencing and 5-aza-2'-deoxycytidine reversal in MSCs

    PMID:20727853

    Open questions at the time
    • Downstream effectors connecting CIP4 level to differentiation unknown
    • Physiological upstream methylation trigger not identified
  8. 2012 High

    Revealed a non-endocytic, lamellipodia-based function of CIP4 in neurons that inhibits neurite initiation, showing CIP4 output is context-dependent on subcellular localization.

    Evidence Overexpression/domain-deletion mutants, CIP4-null neurons, live imaging and morphometry

    PMID:22361215

    Open questions at the time
    • Why neuronal CIP4 favors lamellipodia over endosomes not mechanistically explained at this stage
  9. 2013 High

    Defined the localization logic of CIP4 at protruding edges (PIP3- and actin-architecture-dependent, Rac1/WAVE1-driven) and demonstrated distinct biophysical roles in megakaryocyte membrane deformability and chemotactic directionality.

    Evidence PI3K/Arp2/3 inhibition, capping protein, live imaging in neurons; CIP4-null mice with fluorescence anisotropy and micropipette aspiration in megakaryocytes; siRNA with CCL19 chemotaxis and pathway assays in CLL cells

    PMID:23572514 PMID:23644527 PMID:23881916

    Open questions at the time
    • Switch between Cdc42/N-WASP and Rac1/WAVE1 axes not fully resolved
    • WASP-independent platelet mechanism only partially defined
  10. 2013 High

    Identified an antagonistic relationship between CIP4 and the formin Diaphanous, showing CIP4 can inhibit actin nucleation and stabilize membranes, refining its role beyond simple actin promotion.

    Evidence In vitro actin nucleation assay, genetic epistasis and physical interaction in Drosophila cellularization

    PMID:23424199

    Open questions at the time
    • Mammalian relevance of CIP4-formin antagonism untested
    • Conditions favoring inhibition vs promotion of actin unclear
  11. 2013 Medium

    Established a CIP4 requirement for cardiomyocyte hypertrophic growth and mapped the FCH domain as essential for localization and function.

    Evidence siRNA, recombinant protein rescue and FCH-deletion mutant with hypertrophy readouts in neonatal cardiomyocytes

    PMID:23915320

    Open questions at the time
    • Molecular effectors of CIP4 in hypertrophy not identified at this stage
    • Single neonatal model
  12. 2015 Medium

    Showed AKAP350 recruits CIP4 to the centrosome to organize the nucleus-centrosome-Golgi axis, linking CIP4 to cell polarization machinery distinct from its membrane-curvature roles.

    Evidence Co-IP, siRNA, dominant-negative interaction disruption with centrosome positioning and wound-healing assays

    PMID:26208639

    Open questions at the time
    • How a membrane-curvature protein functions at the centrosome mechanistically unresolved
    • Single lab
  13. 2018 High

    Defined a precise priming mechanism in which Cdc42 recruits CIP4/FBP17 to generate PI(3,4)P2 via SHIP2 and lamellipodin, with GAP-driven transient assembly cycles enabling fast endophilin-mediated endocytosis.

    Evidence Co-localization screen of BAR proteins, co-IP, lipid-product measurement, GTPase activation/deactivation and live-cell imaging

    PMID:30061681

    Open questions at the time
    • Stoichiometry of the priming complex not determined
    • How specific cargoes select FEME unresolved
  14. 2019 High

    Identified PKA phosphorylation at T225 as a regulatory switch that enhances CIP4-CDC42 binding and invadopodia localization, linking CIP4 to cancer cell invasion.

    Evidence In vitro PKA kinase assay with mass spectrometry, phosphomimetic/non-phosphorylatable mutants, invasion/invadopodia assays and CDC42 co-IP

    PMID:31319138

    Open questions at the time
    • Upstream signals activating PKA toward CIP4 in tumors unknown
    • Structural effect of T225 phosphorylation on F-BAR/SH3 unresolved
  15. 2022 Medium

    Connected CIP4-mediated CDC42 recruitment at invadopodia to NF-κB activation and matrix degradation, providing a signaling output for CIP4's pro-metastatic role.

    Evidence GTP-Cdc42 co-IP, knockdown/overexpression, invadopodia and matrix-degradation assays, NF-κB inhibition and in vivo metastasis model in colorectal cancer

    PMID:35317515

    Open questions at the time
    • Mechanistic link from CDC42 recruitment to NF-κB activation not detailed
    • Single lab
  16. 2023 High

    Provided direct structural/mechanical evidence that CIP4 self-assembly via IDRs drives asymmetric clathrin-coated pit closure, and that CIP4 acts as a curvature-radius-dependent mechanosensor organizing CDC42/actin nanodomains that modulate IFNγ JAK/STAT signaling.

    Evidence High-speed AFM, knockout, IDR mutagenesis and super-resolution imaging; engineered nanostructured surfaces with PI(4,5)P2/CDC42 co-localization and JAK/STAT assays

    PMID:37528083 PMID:38091386

    Open questions at the time
    • How IDR self-assembly is regulated in cells unclear
    • Generality of nanodomain-mediated receptor signaling regulation beyond IFNγR untested
  17. 2025 Medium

    Identified a CIP4-organized CaNAβ2 signalosome in cardiomyocytes that drives adverse cardiac remodeling, with disruption peptides recapitulating cardioprotection — extending CIP4 scaffolding to a calcineurin signaling compartment; and a cell-autonomous role in adipocyte lipid accumulation.

    Evidence Cardiac conditional knockout mice, AAV-delivered PP anchoring disruptor peptide/shRNA/VIVIT with ischemia-reperfusion and infarction models (preprint); CRISPR knockdown lipid-accumulation assay in human white adipose cells (preprint)

    PMID:40462891 PMID:bio_10.1101_2024.09.19.24313913

    Open questions at the time
    • Peer review pending for both findings
    • Lipid-accumulation mechanism lacks pathway follow-up
    • How membrane-curvature scaffolding relates to calcineurin anchoring unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CIP4 selects among its alternative effector axes (Cdc42/N-WASP vs Rac1/WAVE1 vs formin antagonism vs calcineurin scaffolding) in a given cell context remains unresolved.
  • No unified model of how localization, phosphorylation, and partner availability switch CIP4 output
  • Structural basis of context-dependent partner selection unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0008092 cytoskeletal protein binding 4 GO:0008289 lipid binding 3 GO:0005198 structural molecule activity 2 GO:0140299 molecular sensor activity 1
Localization
GO:0005886 plasma membrane 4 GO:0005856 cytoskeleton 3 GO:0005768 endosome 2 GO:0005829 cytosol 2 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 6 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 3 R-HSA-1266738 Developmental Biology 2 R-HSA-168256 Immune System 1
Partners
AKAP9CDC42DAAM1DNM2PPP3CBSHIP2WASF1WASL

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 CIP4/2 (TRIP10) was identified as a downstream effector of the GTPase TC10 in insulin-stimulated GLUT4 translocation. CIP4/2 localizes to an intracellular compartment under basal conditions and translocates to the plasma membrane upon insulin stimulation in a TC10-dependent manner; overexpression of dominant-negative TC10 blocks CIP4/2 translocation, and mutant CIP4/2 with diminished TC10 binding inhibits insulin-stimulated GLUT4 translocation. Overexpression of constitutively active and dominant-negative TC10 constructs; subcellular localization studies; functional inhibition via N-terminal deletion and TC10-binding mutants in 3T3L1 adipocytes Proceedings of the National Academy of Sciences of the United States of America Medium 12242347
2006 CIP4 (TRIP10) binds to the diaphanous-related formin DAAM1 via its SH3 domain. DAAM1 also binds RhoA and Cdc42 in a GTP-dependent manner, placing CIP4 in a complex with DAAM1, Rho GTPases, and Src that regulates actin dynamics and cell morphology. Yeast two-hybrid screen; co-immunoprecipitation; GTP-dependent pulldown; ectopic expression with morphological readout Experimental cell research Medium 16630611
2008 Drosophila Cip4 (ortholog of TRIP10) acts as a Cdc42 effector that interacts with Dynamin and the Arp2/3 activator WASp to regulate E-cadherin endocytosis at adherens junctions in epithelial cells. Loss of Cip4, WASp, or Arp2/3 results in defective E-cadherin endocytosis, placing Cip4 downstream of the Cdc42-Par6-aPKC pathway. Genetic loss-of-function in Drosophila; co-immunoprecipitation; epistasis analysis with dynamin mutants; live imaging of endocytic vesicles Current biology : CB High 18976911
2009 Drosophila Cip4/Toca-1 forms a complex with both WASP and SCAR/WAVE, recruits these actin-nucleation-promoting factors to invaginating membranes and endocytic vesicles, and promotes membrane invagination and vesicle scission by recruiting Dynamin. Actin-comet-tail-based vesicle movement depends largely on WAVE. Cdc42 acts upstream of Cip4 to recruit both WASP and WAVE/Abi. Biochemical co-immunoprecipitation; genetic rescue experiments; live imaging; gene dosage epistasis in Drosophila wing Current biology : CB High 19716703
2009 CIP4 (TRIP10) promotes GLUT4 endocytosis in L6 myoblasts by interacting with N-WASp and Dynamin-2 in an insulin-dependent manner. siRNA knockdown of CIP4 increased cell-surface GLUT4 by decreasing its endocytosis. FRET confirmed that CIP4–N-WASp and CIP4–Dynamin-2 interactions are spatially coordinated at the plasma membrane and cytosolic compartments in an insulin-dependent fashion. siRNA knockdown; flow cytometry for surface GLUT4; endogenous co-immunoprecipitation; FRET imaging; 14C-deoxyglucose uptake Journal of cell science High 19509061
2009 CIP4 (TRIP10) localizes to early endosomes via the curved phosphoinositide-binding face of its F-BAR domain and is required for transit of EGFR from EEA1-positive endosomes to lysosomes. CIP4 depletion leads to elevated EGFR levels, enhanced ERK activation, and increased S-phase entry, indicating CIP4 limits sustained ERK signaling through endosomal trafficking regulation. RNA interference; mutagenesis of F-BAR domain; co-localization with Rab5 and EEA1 markers; constitutively active Rab5; flow cytometry; ERK phosphorylation assays; BrdU incorporation Cellular signalling Medium 19632321
2009 CIP4-null mice generated by homologous recombination display delayed and decreased endocytosis (transferrin, FITC-dextran, HRP) in mouse embryonic fibroblasts, demonstrating CIP4 affects multiple modes of endocytosis in vivo. CIP4-null mice also showed enhanced insulin sensitivity with higher GLUT4 in muscle membrane fractions under insulin stimulation. Homologous recombination knockout; transferrin/FITC-dextran/HRP uptake assays; 14C-2-deoxyglucose uptake; membrane fractionation; western blot The Journal of biological chemistry High 19920150
2009 CIP4 (TRIP10) interacts with ArgBP2, and both proteins modulate each other's tyrosine phosphorylation by c-Abl. CIP4 directly interacts with WAVE1 and enhances its phosphorylation by c-Abl; ArgBP2 and CIP4 act synergistically to increase WAVE1 tyrosine phosphorylation. Yeast two-hybrid; co-immunoprecipitation; in vitro phosphorylation assays with c-Abl; cell-based overexpression Cancer letters Medium 19631450
2010 CIP4 (TRIP10) is essential for integrin-dependent T-cell trafficking. CIP4-null mice have impaired T cell adhesion and polarization on VCAM-1 and ICAM-1, defective arrest and transmigration across endothelial monolayers under shear flow, impaired contact hypersensitivity, and defective T cell-dependent antibody production and germinal center formation. CIP4-null mice; adoptive transfer; adhesion assays on immobilized VCAM-1/ICAM-1; transmigration assays under shear flow; contact hypersensitivity model Proceedings of the National Academy of Sciences of the United States of America High 20805498
2010 CIP4 (TRIP10) and the related paralogs FBP17 and Toca-1 promote membrane tubulation downstream of activated Cdc42, with CIP4-dependent tubulation enhanced by activated Cdc42. Knockdown of CIP4-like proteins results in prolonged PDGF-induced dorsal ruffles and increased PDGF-dependent cell migration due to sustained PDGFRβ activation from delayed receptor internalization. siRNA knockdown; membrane tubulation assays; PDGF-stimulated dorsal ruffle imaging; PDGFRβ internalization and activation assays; migration assays Biology of the cell Medium 19909236
2010 DNA methylation of the TRIP10 (CIP4) promoter reduces TRIP10 expression and accelerates mesenchymal stem cell differentiation toward neuron and osteocyte lineages. Treatment with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine reversed suppressed TRIP10 expression, confirming epigenetic regulation of this locus controls MSC fate. In vitro targeted promoter methylation; transfection into MSCs; EGFP reporter system; bisulfite sequencing; 5-aza-2'-deoxycytidine treatment Biochemical and biophysical research communications Medium 20727853
2011 TRIP10/CIP4 overexpression in brain tumor cells associates with endogenous Cdc42 and huntingtin. Overexpression of TRIP10 promoted colony formation and tumorigenesis in IMR-32 (brain tumor) cells but suppressed colony formation in CP70 (ovarian cancer) cells, indicating cell-type-specific roles. Co-immunoprecipitation (Cdc42, huntingtin); colony formation assay; in vivo tumorigenesis in mice Journal of biomedical science Low 21299869
2012 CIP4 (TRIP10) inhibits neurite formation in primary cortical neurons by producing lamellipodial protrusions, rather than through endocytosis. CIP4 localizes to tips of extending lamellipodia and filopodia in neurons (instead of endosomes). This effect requires the F-BAR and SH3 domains and the ability to multimerize. CIP4-null cortical neurons initiate neurites twice as fast as controls. Overexpression and domain deletion mutants; CIP4-null mouse neurons; live imaging; morphometric analysis; co-localization studies Current biology : CB High 22361215
2013 CIP4 (TRIP10) loss in mice causes thrombocytopenia. CIP4-null megakaryocytes show reduced proplatelet protrusions and altered demarcation membrane system. CIP4 loss results in a more rigid membrane (fluorescence anisotropy) and decreased cortical actin tension (micropipette aspiration), indicating CIP4 promotes membrane deformability and cytoskeletal reorganization required for platelet production via a WASP-independent mechanism. CIP4-null mice; electron microscopy; fluorescence anisotropy; micropipette aspiration; siRNA knockdown; platelet counts; proplatelet quantification Blood High 23881916
2013 CIP4 (TRIP10) localizes to protruding edges of neurons dependent on both phosphatidylinositol-(3,4,5)-trisphosphate (PIP3) production and the underlying actin filament architecture. Inhibiting PIP3 decreases CIP4 at the membrane. CIP4 localization at the protruding edge depends on Rac1/WAVE1 (not Cdc42/N-WASP), and capping of actin filaments dramatically reduces CIP4 at the edge. CIP4 dynamically colocalizes with Ena/VASP and DAAM1 at the protruding edge. PI3K inhibition; cytochalasin D; capping protein overexpression; Arp2/3 inhibition; live imaging; co-localization studies in primary cortical neurons Journal of cell science Medium 23572514
2013 Drosophila Cip4/Toca-1 physically and functionally interacts with the formin Diaphanous (Dia). Overexpression of Cip4 phenocopies dia loss-of-function in membrane stabilization. In vitro, Cip4 inhibits actin nucleation by Dia. Dia and Cip4 antagonistically regulate membrane invaginations during Drosophila cellularization. Physical interaction assays; genetic epistasis; in vitro actin nucleation assay; live imaging; loss-of-function genetics in Drosophila Journal of cell science High 23424199
2013 CIP4 (TRIP10) regulates CCL19-driven chemotaxis in chronic lymphocytic leukemia cells. Upon CCL19 stimulation, CIP4 associates with GTP-bound Cdc42 and localizes to the rear of the lamellipodium and along microspikes. CIP4 depletion impairs lamellipodium assembly and directional migration and decreases WASP activation while increasing PAK1 and p38 MAPK activation. p38 MAPK inhibition impairs lamellipodium assembly and directionality. siRNA knockdown; co-immunoprecipitation with GTP-Cdc42; chemotaxis assays; live imaging; western blot for WASP, PAK1, p38 MAPK activation Cancer research Medium 23644527
2013 CIP4 (TRIP10) is required for hypertrophic growth of neonatal cardiac myocytes. CIP4 expression is induced by hypertrophic stimuli (phenylephrine, LIF, FBS), and CIP4 siRNA inhibits hypertrophy induced by these stimuli as measured by cell size, ANF expression, and leucine incorporation. Rescue with recombinant CIP4 restores hypertrophy, but not a mutant lacking the N-terminal FCH domain, indicating the FCH domain is required for CIP4 intracellular localization and function. siRNA knockdown; recombinant protein rescue; FCH domain deletion mutant; morphometry; immunocytochemistry for ANF; [3H]leucine incorporation Journal of biomedical science Medium 23915320
2015 Centrosomal AKAP350 recruits CIP4 (TRIP10) to the centrosome, particularly in migratory cells. CIP4 localizes to the centrosome and is required for nucleus-centrosome-Golgi axis formation and cell migration directionality. Inhibition of the CIP4-AKAP350 interaction or CIP4 depletion causes defective centrosome positioning and cell polarization without affecting nuclear movement. siRNA knockdown; co-immunoprecipitation; dominant-negative disruption of CIP4-AKAP350 interaction; centrosome localization by immunofluorescence; wound-healing migration assays Journal of cell science Medium 26208639
2018 CIP4 (TRIP10) and FBP17 prime the plasma membrane for fast endophilin-mediated endocytosis (FEME) by recruiting the 5'-lipid phosphatase SHIP2 and lamellipodin to generate local phosphatidylinositol-3,4-bisphosphate (PI(3,4)P2) and enable endophilin pre-enrichment. Membrane-bound GTP-loaded Cdc42 recruits FBP17 and CIP4 to these sites, after which RICH1 and SH3BP1 GAPs locally deactivate Cdc42, generating transient 5–10 second assembly/disassembly cycles that prime membrane patches for FEME. Co-localization of 65 BAR-domain proteins with endophilin; co-immunoprecipitation; SHIP2 and lamellipodin recruitment assays; PI(3,4)P2 production measurement; GTPase activation/deactivation assays; live-cell imaging Nature cell biology High 30061681
2019 CIP4 T225 is the major PKA phosphorylation site. A CIP4(T225E) phosphomimetic mutant increases cancer cell metastatic capacity and invadopodia formation, while CIP4(T225A) reduces invasive properties. T225 phosphorylation enhances CIP4 localization to invadopodia and facilitates CIP4 interaction with CDC42. PKA inhibition reduces migration/invasion to CIP4(T225A) levels but not in cells expressing CIP4(T225E). In vitro PKA phosphorylation assay with mass spectrometry; phosphomimetic and non-phosphorylatable mutants; invasion and migration assays; invadopodia formation assay; PKA inhibitors; co-immunoprecipitation with CDC42 Cancer letters High 31319138
2022 CIP4 (TRIP10) directly binds GTP-Cdc42 and recruits it to invadopodia; CIP4 overexpression promotes invadopodia formation and matrix degradation via activation of the NF-κB signaling pathway. Inhibition of either CIP4 or Cdc42 suppresses NF-κB activation and reduces invadopodia quantity in colorectal cancer cells. Co-immunoprecipitation with GTP-Cdc42; CIP4 knockdown and overexpression; invadopodia formation assays; matrix degradation assays; NF-κB pathway inhibition; in vivo metastasis model Molecular therapy oncolytics Medium 35317515
2023 CIP4 (TRIP10) self-assembles via intrinsically disordered regions (IDRs), and this self-assembly together with stereospecific interactions with curved membranes and actin-regulating proteins drives asymmetric pit-closing during clathrin-mediated endocytosis. High-speed atomic force microscopy demonstrated that CIP4 is necessary for asymmetric (not radial) closure of clathrin-coated pits by generating a small actin-rich environment near the pit. High-speed atomic force microscopy; CIP4 knockout; IDR mutagenesis; live-cell super-resolution imaging Nature communications High 37528083
2023 CIP4 (TRIP10) and PI(4,5)P2 mediate the formation of dynamic actin structures at sites of plasma membrane nanodeformation through CDC42 recruitment. CIP4 acts as a mechanosensor of membrane curvature, binding membrane deformations in a curvature radius-dependent manner. These CIP4/CDC42/actin-enriched nanodomains contain IFNγ receptor and partially inhibit IFNγ-induced JAK/STAT signaling. Fluorescent nanostructured cell culture surfaces; live imaging; siRNA knockdown; co-localization with CDC42 and PI(4,5)P2; JAK/STAT signaling assays Science advances Medium 38091386
2025 CIP4 (TRIP10) organizes a CaNAβ2 (calcineurin Aβ2) signaling compartment in cardiomyocytes via direct binding through the CaNAβ-specific N-terminal polyproline (PP) domain. CIP4 cardiac conditional knockout mice exhibit preserved cardiac function and decreased infarct size after ischemia-reperfusion injury and myocardial infarction. A CaNAβ2 PP anchoring disruptor peptide that blocks CIP4-CaNAβ2 binding recapitulates the cardioprotective benefit, indicating that CIP4-CaNAβ2 signalosomes promote adverse cardiac remodeling. CIP4 conditional knockout mice; echocardiography; AAV-mediated cardiomyocyte-specific expression of PP anchoring disruptor peptide, CaNAβ2 shRNA, and VIVIT; ischemia-reperfusion surgery; permanent coronary artery ligation; histology; in vitro T-cell activation assay bioRxivpreprint Medium 40462891
2024 CRISPR knockdown of TRIP10 in human white adipose tissue cell lines increased lipid accumulation (fold change 1.39, p=0.016), demonstrating a cell-autonomous role for TRIP10 in regulating lipid accumulation. CRISPR knockdown in human white adipose tissue cell lines; lipid accumulation assay bioRxivpreprint Low bio_10.1101_2024.09.19.24313913
2025 CIP4 (TRIP10) and FBP17 are required for proper radial migration of cortical neurons in vivo. Either knockdown or overexpression of CIP4 disrupts radial migration by altering neuronal morphology and neurite outgrowth, consistent with roles in regulating transitions between bipolar and multipolar states during migration. In utero electroporation; Double UP technique for comparing knockdown/overexpression to controls within same tissue; in vivo mouse cortical development The Journal of neuroscience Medium 40721321

Source papers

Stage 0 corpus · 34 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Drosophila Cip4 and WASp define a branch of the Cdc42-Par6-aPKC pathway regulating E-cadherin endocytosis. Current biology : CB 192 18976911
2009 Drosophila Cip4/Toca-1 integrates membrane trafficking and actin dynamics through WASP and SCAR/WAVE. Current biology : CB 116 19716703
2006 The diaphanous-related formin DAAM1 collaborates with the Rho GTPases RhoA and Cdc42, CIP4 and Src in regulating cell morphogenesis and actin dynamics. Experimental cell research 92 16630611
2018 FBP17 and CIP4 recruit SHIP2 and lamellipodin to prime the plasma membrane for fast endophilin-mediated endocytosis. Nature cell biology 78 30061681
2002 The TC10-interacting protein CIP4/2 is required for insulin-stimulated Glut4 translocation in 3T3L1 adipocytes. Proceedings of the National Academy of Sciences of the United States of America 78 12242347
2009 The F-BAR protein CIP4 promotes GLUT4 endocytosis through bidirectional interactions with N-WASp and Dynamin-2. Journal of cell science 53 19509061
2009 The Cdc42-interacting protein-4 (CIP4) gene knock-out mouse reveals delayed and decreased endocytosis. The Journal of biological chemistry 49 19920150
2013 The F-BAR protein Cip4/Toca-1 antagonizes the formin Diaphanous in membrane stabilization and compartmentalization. Journal of cell science 46 23424199
2010 DNA methylation of the Trip10 promoter accelerates mesenchymal stem cell lineage determination. Biochemical and biophysical research communications 43 20727853
2012 The F-BAR protein CIP4 inhibits neurite formation by producing lamellipodial protrusions. Current biology : CB 42 22361215
2009 F-BAR-containing adaptor CIP4 localizes to early endosomes and regulates Epidermal Growth Factor Receptor trafficking and downregulation. Cellular signalling 37 19632321
2013 Loss of the F-BAR protein CIP4 reduces platelet production by impairing membrane-cytoskeleton remodeling. Blood 33 23881916
2003 Role for Fes/Fps tyrosine kinase in microtubule nucleation through is Fes/CIP4 homology domain. The Journal of biological chemistry 33 14551201
2015 Centrosomal AKAP350 and CIP4 act in concert to define the polarized localization of the centrosome and Golgi in migratory cells. Journal of cell science 28 26208639
2010 Members of the CIP4 family of proteins participate in the regulation of platelet-derived growth factor receptor-beta-dependent actin reorganization and migration. Biology of the cell 28 19909236
2008 High-fat diet alters PP2A, TC10, and CIP4 expression in visceral adipose tissue of rats. Obesity (Silver Spring, Md.) 28 18388891
2019 Identification of a CIP4 PKA phosphorylation site involved in the regulation of cancer cell invasiveness and metastasis. Cancer letters 27 31319138
2010 Cdc42 interacting protein 4 (CIP4) is essential for integrin-dependent T-cell trafficking. Proceedings of the National Academy of Sciences of the United States of America 27 20805498
2013 CIP4 coordinates with phospholipids and actin-associated proteins to localize to the protruding edge and produce actin ribs and veils. Journal of cell science 24 23572514
2011 Functional characterization of Trip10 in cancer cell growth and survival. Journal of biomedical science 24 21299869
2009 CIP4 is a new ArgBP2 interacting protein that modulates the ArgBP2 mediated control of WAVE1 phosphorylation and cancer cell migration. Cancer letters 22 19631450
2015 Cooperative functions of the two F-BAR proteins Cip4 and Nostrin in the regulation of E-cadherin in epithelial morphogenesis. Journal of cell science 21 25413347
2015 Protective effects of calcitriol on diabetic nephropathy are mediated by down regulation of TGF-β1 and CIP4 in diabetic nephropathy rat. International journal of clinical and experimental pathology 18 26097534
2013 CIP4 controls CCL19-driven cell steering and chemotaxis in chronic lymphocytic leukemia. Cancer research 18 23644527
2023 Plasma membrane nanodeformations promote actin polymerization through CIP4/CDC42 recruitment and regulate type II IFN signaling. Science advances 14 38091386
2023 Self-assembly of CIP4 drives actin-mediated asymmetric pit-closing in clathrin-mediated endocytosis. Nature communications 13 37528083
2013 Inhibition of Cdc42-interacting protein 4 (CIP4) impairs osteosarcoma tumor progression. Current cancer drug targets 13 22920438
2013 CIP4 is required for the hypertrophic growth of neonatal cardiac myocytes. Journal of biomedical science 10 23915320
2017 Suppression of CIP4/Par6 attenuates TGF-β1-induced epithelial-mesenchymal transition in NRK-52E cells. International journal of molecular medicine 9 28848997
2013 Role of CIP4 in high glucose induced epithelial--mesenchymal transition of rat peritoneal mesothelial cells. Renal failure 9 23819628
2022 CIP4 targeted to recruit GTP-Cdc42 involving in invadopodia formation via NF-κB signaling pathway promotes invasion and metastasis of CRC. Molecular therapy oncolytics 8 35317515
2024 F-BAR proteins CIP4 and FBP17 function in cortical neuron radial migration and process outgrowth. bioRxiv : the preprint server for biology 1 39484544
2025 Targeting of CIP4-Calcineurin Signalosomes Improves Cardiac Structure and Function After Myocardial Infarction. bioRxiv : the preprint server for biology 0 40462891
2025 F-BAR Proteins CIP4 and FBP17 Function in Cortical Neuron Radial Migration and Process Outgrowth. The Journal of neuroscience : the official journal of the Society for Neuroscience 0 40721321

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