Affinage

CDC42

Cell division control protein 42 homolog · UniProt P60953

Round 2 corrected
Length
191 aa
Mass
21.3 kDa
Annotated
2026-04-28
130 papers in source corpus 59 papers cited in narrative 59 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CDC42 is a Rho-family small GTPase that functions as a master regulator of cell polarity, actin cytoskeleton remodeling, directed migration, and mitotic fidelity by cycling between GDP-bound (inactive) and GTP-bound (active) states under the control of GEFs (Dbl, Vav2, Ect2, Cdc24/Bem1), GAPs (CDC42Hs-GAP, srGAPs, MgcRacGAP), and RhoGDI, which sequesters isoprenylated CDC42 in the cytosol via the Rho-insert region (PMID:1429634, PMID:9334181, PMID:8626553). GTP-bound CDC42 engages a diverse effector network — PAK kinases to activate JNK/p38 cascades and phosphorylate merlin, WASP/N-WASP to relieve autoinhibition and stimulate Arp2/3-dependent actin polymerization and filopodium formation, IQGAP1 to capture microtubule plus-ends via CLIP-170 for cell polarization, Par6–aPKC to establish epithelial apical polarity and lumen formation, and Sec3/exocyst to direct polarized secretion (PMID:8107774, PMID:10724160, PMID:12110184, PMID:10934474, PMID:18195105). CDC42 acts as a spatial compass during chemotaxis, with excitable local CDC42 signals preceding and predicting cell turning direction, and is required for mitotic spindle–kinetochore attachment via Ect2/MgcRacGAP-regulated GTPase cycling (PMID:26689677, PMID:15642749). Germline missense variants that alter CDC42 GTP cycling or effector engagement cause a clinically heterogeneous developmental syndrome (PMID:29394990).

Mechanistic history

Synthesis pass · year-by-year structured walk · 25 steps
  1. 1990 High

    Establishing that CDC42 is post-translationally isoprenylated revealed how this soluble GTPase achieves membrane association, a prerequisite for all subsequent spatial signaling studies.

    Evidence Metabolic [³H]mevalonate labeling and lovastatin treatment with subcellular fractionation in mammalian cells

    PMID:2120220

    Open questions at the time
    • Identity of the specific prenyl group (geranylgeranyl vs. farnesyl) was not resolved in this study
    • How membrane association feeds back on GTPase cycling was unknown
  2. 1991 High

    Identification and purification of a specific GAP for CDC42Hs from human platelets established that the GTP hydrolysis rate of CDC42 is extrinsically regulated, and that the oncogenic V12 mutant escapes GAP stimulation.

    Evidence Biochemical purification (~3500-fold) and GTPase activity assay with purified CDC42Hs-GAP

    PMID:1939135

    Open questions at the time
    • Molecular identity of CDC42Hs-GAP not cloned
    • In vivo relevance not demonstrated
  3. 1992 High

    Identification of RhoGDI as the inhibitor of CDC42Hs GDP dissociation and its role in extracting CDC42 from membranes defined the third arm (GDI) of the canonical GTPase regulatory triad.

    Evidence Purification from bovine brain, GDP dissociation assay, membrane extraction assay

    PMID:1429634

    Open questions at the time
    • Structural basis of GDI–CDC42 interaction unknown
    • How GDI selectivity among Rho GTPases is achieved was unclear
  4. 1994 High

    Discovery that GTP-bound CDC42 directly binds and activates the PAK serine/threonine kinase identified the first effector kinase, linking CDC42 to phosphorylation-dependent signaling cascades.

    Evidence Biochemical purification from brain, GTP-dependent binding and kinase autophosphorylation assay

    PMID:8107774

    Open questions at the time
    • In vivo substrates of PAK downstream of CDC42 were unknown
    • Whether PAK activation requires membrane context was untested
  5. 1994 High

    Demonstration that CDC42 directly stimulates PI 3-kinase via the p85 subunit expanded the effector repertoire beyond kinases to lipid signaling, using effector-domain mutagenesis to prove direct engagement.

    Evidence GST pulldown, recombinant protein binding, immunoprecipitation kinase assay with T35A mutant

    PMID:8034624

    Open questions at the time
    • Physiological context for CDC42–PI3K signaling not defined
    • Whether other Rho GTPases compete for p85 binding in vivo was unknown
  6. 1995 High

    Placing CDC42 upstream of the JNK/p38 MAPK cascades (but not ERK) and independently upstream of SRF-mediated transcription established that CDC42 controls nuclear gene expression through at least two distinct signaling arms.

    Evidence Constitutively active/dominant-negative mutant expression with kinase and reporter assays in mammalian cells

    PMID:7600582 PMID:7600583

    Open questions at the time
    • Intermediate kinases between CDC42 and MEKK were not identified
    • How SRF activation proceeds independently of all three MAPK branches was unclear
  7. 1995 High

    Definition of the CRIB (Cdc42/Rac-interactive binding) motif across >25 proteins provided a universal sequence-based framework for predicting and validating CDC42 effectors.

    Evidence Motif-based database search validated by filter binding assay with recombinant proteins

    PMID:7493928

    Open questions at the time
    • Not all CRIB-containing proteins were functionally validated as effectors
    • Structural basis of CRIB–CDC42 recognition not yet solved
  8. 1996 High

    Quantitative fluorescence spectroscopy showed RhoGDI binds CDC42 with ~30 nM affinity regardless of nucleotide state but requires C-terminal isoprenylation and the Rho-insert region, resolving how GDI discriminates CDC42 from non-Rho GTPases.

    Evidence Fluorescence titration with prenylated and unprenylated CDC42, truncation mutants, Rho-insert chimeras

    PMID:8626553 PMID:9334181

    Open questions at the time
    • Crystal structure of the GDI–CDC42 complex not available
    • Mechanism of GDI release at membranes was unknown
  9. 1996 High

    Identification of WASP as a CDC42-specific effector linked CDC42 to actin polymerization and the Wiskott-Aldrich syndrome, and identification of IQGAP1 as a CDC42-binding scaffolding protein revealed a distinct mechanism for sustaining active CDC42.

    Evidence Co-immunoprecipitation, GTP-dependent binding, dominant-negative epistasis for WASP; affinity chromatography, GTPase assay, yeast genetics for IQGAP1

    PMID:8625410 PMID:8670801

    Open questions at the time
    • How WASP activation leads to Arp2/3 engagement was not yet understood
    • IQGAP1's downstream cellular functions were unclear
  10. 1998 High

    Reconstitution of the CDC42–N-WASP–actin axis in a cell-free system, combined with NMR mapping of the CDC42–PAK interface and integrin-CDC42-Rac epistasis, provided the structural and signaling logic for how CDC42 drives filopodia formation and cell spreading.

    Evidence Cell-free actin polymerization, heteronuclear NMR, integrin adhesion/spreading assays with dominant-negative mutants

    PMID:9422512 PMID:9658176 PMID:9760238

    Open questions at the time
    • Full atomic structure of CDC42–N-WASP–Arp2/3 complex not solved
    • How integrin engagement activates CDC42 at a molecular level was unknown
  11. 1998 High

    Discovery that CDC42 is required for directional sensing during chemotaxis — distinct from migration per se — established CDC42 as the molecular compass for directed cell movement.

    Evidence Microinjection of dominant-negative N17Cdc42 into macrophages, Dunn chemotaxis chamber with CSF-1 gradient

    PMID:9606207

    Open questions at the time
    • How CDC42 senses chemoattractant gradients at the molecular level was unknown
    • Whether CDC42 acts cell-autonomously as a polarity cue or amplifies an upstream signal was unresolved
  12. 2000 High

    NMR structure of autoinhibited WASP and its release by CDC42 binding, together with identification of the Par6–CDC42–aPKC–Par3 polarity complex, established the two cardinal effector mechanisms: actin assembly via WASP autoinhibition relief and epithelial polarity via the PAR module.

    Evidence NMR structure of WASP GBD–VCA; co-immunoprecipitation, yeast two-hybrid, tight junction assay for Par6–aPKC

    PMID:10724160 PMID:10934474

    Open questions at the time
    • How Par6–CDC42 binding activates aPKC was not structurally resolved
    • Whether WASP and Par6 compete for CDC42 in vivo was untested
  13. 2002 High

    Discovery that CDC42/IQGAP1/CLIP-170 form a tripartite complex to capture microtubule plus-ends at the cortex revealed how CDC42 integrates actin and microtubule polarity, while IQGAP1 was shown to actively sustain CDC42-GTP levels.

    Evidence Reciprocal co-immunoprecipitation, pull-down, GFP imaging, IQGAP1 truncation mutants, GTP-CDC42 pull-down

    PMID:11948177 PMID:12110184

    Open questions at the time
    • Whether IQGAP1 acts as a true GDI or inhibits intrinsic GTPase was debated
    • Structural basis of the IQGAP1 GRD–CDC42 interface not resolved
  14. 2003 High

    Linking CDC42 to EGFR downregulation via the Cool-1/βPix–c-Cbl complex explained how constitutively active CDC42 causes sustained receptor signaling and transformation, providing a non-cytoskeletal oncogenic mechanism.

    Evidence Co-immunoprecipitation, ubiquitination and receptor degradation assays, CDC42(F28L) transformation assays

    PMID:14505571

    Open questions at the time
    • Generalizability to other receptor tyrosine kinases was unknown
    • Whether this pathway operates in primary tumors was untested
  15. 2005 High

    Live imaging of GTPase activity zones during wound healing, and biochemical timing of Ect2/MgcRacGAP-regulated CDC42 cycling during mitosis, established that CDC42 spatiotemporal activation is tightly controlled during both wound closure and chromosome segregation.

    Evidence FRET/CRIB biosensors in Xenopus oocytes; GTP-CDC42 pull-down, RNAi, live imaging in mammalian cells

    PMID:15642749 PMID:15684032

    Open questions at the time
    • Molecular basis of CDC42–RhoA crosstalk at wound margins was unknown
    • How Ect2 activation is restricted to metaphase was unclear
  16. 2007 High

    Placing CDC42 upstream of apical lumen formation via PTEN/Annexin2/PIP2, and linking it to Golgi actin remodeling via FMNL2/3 formins, extended CDC42's polarity role from planar migration to three-dimensional morphogenesis and secretory pathway organization.

    Evidence 3D cyst culture with conditional knockdowns and ordered epistasis; CRISPR KO and VSV-G trafficking assay

    PMID:17254974 PMID:28852060

    Open questions at the time
    • How PIP2-recruited CDC42 is activated at the apical surface was unresolved
    • Relative contributions of FMNL2 vs. FMNL3 to Golgi integrity were not separated
  17. 2009 High

    Conditional Cdc42 knockout in mouse pancreas demonstrated that CDC42 is essential for tubulogenesis and non-cell-autonomously influences multipotent progenitor fate, establishing an in vivo organogenesis requirement.

    Evidence Conditional knockout mice, live imaging, immunofluorescence of developing pancreas

    PMID:19914171

    Open questions at the time
    • Specific effectors mediating the non-cell-autonomous effect were not identified
    • Whether the tubulogenesis defect is apical polarity– or secretion-dependent was unclear
  18. 2013 High

    Convergent studies in yeast and vertebrates established feedback loops governing CDC42 polarity: septins recruited by CDC42 feed back to inhibit it via GAPs in yeast, while CDC42–exocyst interaction at primary cilia and Polo-kinase-mediated CDC42 downregulation during cytokinesis demonstrated context-dependent negative regulation.

    Evidence Live imaging with computational modeling in yeast; zebrafish morpholino synergy; Polo analog-sensitive allele with Cdc42 activity assay

    PMID:23766535 PMID:23878274 PMID:23906065

    Open questions at the time
    • Identity of the specific GAPs mediating septin feedback was not fully resolved
    • How Polo kinase suppresses CDC42 biochemically (direct or indirect) was unclear
  19. 2015 High

    FRET biosensor imaging in chemotaxing neutrophils showed that local CDC42 activity precedes cell turning and acts as an excitable compass, confirming at single-cell resolution the directional sensing role proposed from earlier dominant-negative studies.

    Evidence FRET biosensors with photorelease of chemoattractant in PLB-985 cells

    PMID:26689677

    Open questions at the time
    • Molecular mechanism coupling receptor signaling to local CDC42 excitability was unknown
    • Whether the excitable CDC42 signal requires GEF waves or intrinsic GTPase dynamics was unresolved
  20. 2016 High

    Crystal structure of CDC42·GTP bound to the IQGAP2 GRD dimer revealed two distinct CDC42-binding sites per GRD dimer, uniquely enabling CDC42 (but not Rac1) to promote IQGAP dimerization — explaining the specificity of CDC42-IQGAP scaffolding.

    Evidence X-ray crystallography, ITC, mutagenesis comparing CDC42 and Rac1 binding

    PMID:27524202

    Open questions at the time
    • Whether dimerization-dependent IQGAP activation occurs in vivo was untested
    • Structural basis for why Rac1 engages only one site was not fully explained
  21. 2017 High

    Optogenetic spatial perturbation showed that CDC42 activity gradients are set by GEF distribution, and Bem1/Cdc24 reconstitution revealed a PAK-dependent phosphorylation feedback that self-limits GEF activity, together defining the core logic of CDC42 gradient formation and homeostasis.

    Evidence Optogenetics with micropatterning and FRET biosensors; in vitro GEF assay with phosphorylation switch and live yeast imaging

    PMID:28304276 PMID:30446664

    Open questions at the time
    • Whether the Bem1 feedback operates in metazoan cells was untested
    • How GEF localization is initially established remains incompletely understood
  22. 2018 High

    Identification of germline CDC42 missense variants causing a heterogeneous developmental syndrome provided direct human genetic evidence that CDC42 GTPase cycling and effector engagement are essential for normal development.

    Evidence Patient exome sequencing, in vitro GTPase and effector binding assays, zebrafish modeling

    PMID:29394990

    Open questions at the time
    • Genotype–phenotype correlations are incomplete
    • Which effector pathways are most affected by each variant was not resolved
  23. 2019 High

    Endothelial-specific CDC42 deletion producing cerebral cavernous malformations via MEKK3–ERK5–KLF4 derepression linked CDC42 to a clinically relevant vascular disease pathway and identified CCM3 as a CDC42 activator.

    Evidence Inducible endothelial-specific KO mice, co-immunoprecipitation, genetic co-inactivation of Klf4

    PMID:30732528

    Open questions at the time
    • Whether CDC42 loss-of-function variants in humans cause CCM is unknown
    • How CCM3 activates CDC42 at a biochemical level was not defined
  24. 2022 Medium

    Discovery that the microprotein pTINCR promotes CDC42 SUMOylation to activate it during epithelial differentiation introduced post-translational modification of CDC42 beyond isoprenylation and carboxyl-methylation.

    Evidence Co-immunoprecipitation, SUMOylation assay, SIM-domain mutant loss-of-function, patient-derived xenografts

    PMID:36369429

    Open questions at the time
    • SUMOylation site(s) on CDC42 not mapped
    • Independent replication of pTINCR–CDC42 interaction needed
    • Whether SUMOylation alters effector selectivity is unknown
  25. 2023 Medium

    Linking CDC42 to mTORC2/NDRG1-dependent mitochondrial fission expanded CDC42's functional repertoire to organelle dynamics beyond the actin cytoskeleton and polarity.

    Evidence Time-lapse imaging, siRNA epistasis, phospho-mutant analysis in mammalian cells

    PMID:37386153

    Open questions at the time
    • CDC42's direct molecular contribution (effector, GEF) to mitochondrial fission is not identified
    • Whether this reflects a general role or is context-specific is unknown
    • Single study — independent confirmation needed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include how CDC42 effector selectivity is spatiotemporally determined in vivo, whether SUMOylation and other non-canonical modifications broadly tune CDC42 signaling, and the full genotype–phenotype map for human CDC42 developmental syndrome variants.
  • No systematic in vivo effector competition model exists
  • Structural basis of CDC42-selective GEF activation in metazoan polarity is incomplete
  • Disease mechanism for each CDC42 variant allele not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 6 GO:0003924 GTPase activity 5 GO:0008092 cytoskeletal protein binding 4
Localization
GO:0005886 plasma membrane 5 GO:0005829 cytosol 3 GO:0005794 Golgi apparatus 2 GO:0005929 cilium 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-1266738 Developmental Biology 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-1500931 Cell-Cell communication 2 R-HSA-1640170 Cell Cycle 2
Partners
ARHGDIAIQGAP1N-WASPPAK1PAK4PAR6SRGAP1WASP
Complex memberships
Exocyst (via Sec3)IQGAP1–CLIP-170 cortical capture complexPar6–aPKC–Par3 polarity complex

Evidence

Reading pass · 59 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 CDC42Hs binds to and activates a brain serine/threonine protein kinase (PAK) related to yeast STE20; GTP-bound CDC42 complexes with PAK, inhibits its GTPase activity, and triggers kinase autophosphorylation and activation. Autophosphorylated PAK has decreased affinity for CDC42, freeing it for further activities. Biochemical purification, GTP-dependent binding assay, kinase autophosphorylation assay Nature High 8107774
1994 GTP-bound CDC42Hs directly associates with the p85 subunit of PI 3-kinase through the Rho-GAP homology domain of p85, and stimulates PI 3-kinase activity 2–4 fold; interaction requires the effector domain of CDC42Hs (T35A mutant abolishes binding). GST pulldown from cell lysates, recombinant protein binding, anti-p85 immunoprecipitation kinase assay The Journal of biological chemistry High 8034624
1994 Fluorescence spectroscopy of mant-GDP bound to CDC42Hs revealed the GTP-binding/GTPase cycle: exchange of mant-dGDP is inhibited by mM Mg2+, stimulated by the Dbl exchange factor, and GTP hydrolysis produces ~30% enhancement of intrinsic Trp97 fluorescence; these assays enabled quantitative mechanistic characterization of CDC42 nucleotide cycling. Fluorescence spectroscopy, filter-binding GTPase assay Biochemistry High 7918454
1992 A GDP-dissociation inhibitor (GDI) for CDC42Hs was purified from bovine brain cytosol and identified as rho-GDI; it inhibits GDP dissociation from CDC42Hs (blocking Dbl-catalyzed exchange), stimulates release of CDC42Hs from plasma membranes, and requires the C-terminal region of CDC42Hs for activity. Biochemical purification, peptide sequencing, GDP dissociation assay, membrane extraction assay The Journal of biological chemistry High 1429634
1991 A GTPase-activating protein (GAP) for CDC42Hs was identified and purified ~3500-fold from human platelet membranes; CDC42Hs-GAP stimulates GTP hydrolysis of CDC42Hs but not of Ras or Rap, and the Val12 mutant of CDC42Hs is resistant to GAP stimulation. Biochemical purification, GTPase activity assay The Journal of biological chemistry High 1939135
1995 Constitutively active Rac and CDC42Hs (but not RhoA) selectively activate the JNK and p38/Mpk2 MAP kinase cascades; dominant-interfering Rac1 places it between Ha-Ras and MEKK in the JNK pathway; neither GTPase activates ERK. Transfection of constitutively active/dominant-negative mutants, kinase assays Cell High 7600582
1995 Activated CDC42Hs (and Rac1 and RhoA) stimulate transcription through SRF at the c-fos serum response element; CDC42Hs-induced SRF activation is independent of ERK, SAPK/JNK, and MPK2/p38 activation, defining a novel Rho-mediated nuclear signaling pathway. Reporter gene assays, dominant-negative/constitutively active mutant expression, kinase assays Cell High 7600583
1996 WASP (Wiskott-Aldrich syndrome protein) was identified as a specific effector for CDC42Hs (not Rac or Rho); interaction requires the GTPase-binding domain of WASP and is GTP-dependent. CDC42Hs-WASP interaction links CDC42Hs to actin polymerization, and dominant-negative CDC42Hs blocks WASP-induced actin clustering. Co-immunoprecipitation, dominant-negative epistasis, immunofluorescence Cell High 8625410
1996 IQGAP1 (p195) was purified from cell lysates on immobilized CDC42Hs-GTP and shown to bind CDC42 and Rac in a GTP-dependent manner; IQGAP1 inhibits GTPase activity of CDC42Hs; it co-immunoprecipitates with CDC42 from cells; its GRD-containing C-terminal half is required for binding; and expression of its GRD inhibits the CDC24/CDC42 pathway in yeast. Affinity chromatography purification, GTPase activity assay, co-immunoprecipitation, yeast genetics The EMBO journal High 8670801
1995 A conserved CRIB (Cdc42/Rac interactive binding) motif was identified in >25 proteins across species; proteins containing CRIB motifs (including PAK isoforms) bind the GTP-bound form of CDC42 and Rac (but not Rho) in a nucleotide-dependent manner, defining a class of CDC42/Rac effector proteins. Motif-based database search, filter binding assay with recombinant proteins The Journal of biological chemistry High 7493928
1995 Three proteins in neutrophil cytosol (p65/hPAK65, p62, p68) bind Rac1 and CDC42Hs in a GTP-dependent manner; hPAK65 (related to rat PAK65 and yeast STE20) undergoes CDC42Hs/Rac1-induced autophosphorylation on serine residues, which activates it toward myelin basic protein; once activated, hPAK65 remains active without continued GTPase binding. Biochemical purification, peptide sequencing, cDNA cloning, autophosphorylation assay, kinase assay The EMBO journal High 7744004
1996 Fluorescence spectroscopy established that RhoGDI binds CDC42Hs with equal affinity in GDP- and GTP-bound states (Kd ~30 nM); the interaction requires isoprenylation of CDC42Hs and its C-terminal 8 amino acids; GDI binding quenches mant-GDP fluorescence, providing a direct assay for the interaction. Fluorescence spectroscopy titration, truncation mutants, Kd measurement The Journal of biological chemistry High 8626553
1997 The Rho insert region (residues 122-134) of CDC42Hs is specifically required for GDI-mediated inhibition of GDP dissociation and GTP hydrolysis, and for GDI-stimulated membrane extraction; it is dispensable for effector/target interactions, GEF (Dbl) interaction, and GAP interaction. CDC42Hs/Ha-Ras chimera construction, GDP dissociation assay, membrane extraction assay, GDI binding assay The Journal of biological chemistry High 9334181
1997 The Cdc42Hs(F28L) fast-cycling mutant (spontaneous GTP-GDP exchange with retained GTPase activity) activates JNK1, stimulates filopodia formation, and transforms NIH 3T3 cells (reduced contact inhibition, serum independence, anchorage-independent growth), demonstrating that Cdc42Hs can act as an oncogene. Site-directed mutagenesis, JNK kinase assay, focus formation, soft-agar assay Current biology High 9368762
1997 The Rho-insert region of CDC42Hs mediates interaction with RhoGDI; the effector domain (D38E mutation) and Y32K mutation affect PAK (mPAK-3) PBD binding; PAK-PBD inhibits both GTPase activity and guanine nucleotide dissociation from CDC42Hs; CDC42-GAP and PBD compete for overlapping sites on CDC42Hs. Fluorescence spectroscopy, mutagenesis, competitive binding assays Biochemistry High 9033409
1998 PAK4 was identified as a CDC42Hs-specific effector (not Rac or Rho); PAK4 binds only activated CDC42Hs through its GBD; co-expression with constitutively active CDC42HsV12 redistributes PAK4 to Golgi membranes and induces filopodia and actin polymerization in a PAK4 kinase-activity-dependent manner. Co-immunoprecipitation, GBD binding assay, immunofluorescence, kinase-dead mutant analysis The EMBO journal High 9822598
1998 N-WASP, a CDC42-interacting protein, induces extremely long actin microspikes only when co-expressed with active CDC42; in a cell-free system, active CDC42 stimulates the actin-depolymerizing activity of N-WASP, creating free barbed ends for actin polymerization. This defines the CDC42–N-WASP–Arp2/3 axis for filopodium formation. Co-expression, cell-free actin polymerization assay, dominant-negative epistasis Nature High 9422512
1998 CDC42Hs and Rac1 directly stimulate phospholipase C-β2 (PLCβ2) via their effector domain (F37A and Y40C mutants abolish stimulation); stimulation requires C-terminal processing of CDC42Hs/Rac1 but is independent of LyGDI; purified recombinant proteins reconstitute stimulation, identifying PLCβ2 as a novel direct effector. Reconstitution with purified recombinant proteins, effector-domain mutagenesis, PLC activity assay The EMBO journal High 9799233
1998 NMR spectroscopy mapped the PAK binding surface on CDC42Hs·GMPPCP to the second β-strand (β2) and the switch I loop (α1-β2 loop); PBD46 binding produces structural changes throughout CDC42Hs beyond the direct interface, explaining its inhibition of GTP hydrolysis. Heteronuclear NMR, deuterium labeling, chemical shift perturbation Biochemistry High 9760238
1998 Integrin-dependent adhesion to fibronectin leads to rapid activation of PAK (a downstream effector of CDC42 and Rac); dominant-negative CDC42 inhibits filopodia-like projections during spreading, and dominant-negative Rac inhibits lamellipodia; epistasis shows integrins activate CDC42 first, which then activates Rac to drive cell spreading. Dominant-negative mutant expression, PAK activity assay, morphological analysis Molecular biology of the cell High 9658176
1998 CDC42 is required for directional chemotaxis toward CSF-1 in macrophages: dominant-negative N17Cdc42 cells can migrate but cannot polarize in the direction of a CSF-1 gradient, abolishing chemotaxis; Rho and Rac are required for migration speed but not for directional sensing. Microinjection of dominant-negative mutants, Dunn chemotaxis chamber The Journal of cell biology High 9606207
2000 Par6 forms a complex with CDC42-GTP, the PAR-3 homologue, and the regulatory domains of atypical PKC (aPKC); this tripartite complex is required for normal tight junction formation, linking CDC42 to the PAR polarity machinery and aPKC signaling. Co-immunoprecipitation, yeast two-hybrid, dominant-negative epistasis, tight junction assay Nature cell biology High 10934474
2000 Autoinhibition of WASP involves an intramolecular interaction between the GTPase-binding domain (GBD) and the C-terminal VCA region; CDC42 binding to the GBD causes a dramatic conformational change that disrupts the autoinhibited state and releases the VCA region to activate the Arp2/3 complex. NMR structure determination, biochemical binding assays, mutagenesis Nature High 10724160
2000 Vav2 functions as a guanine nucleotide exchange factor (GEF) for CDC42, Rac1, and RhoA in vitro; constitutively active Vav2 causes transformation, lamellipodia formation, and JNK activation requiring CDC42, Rac1, and RhoA activity. In vitro GEF assay, transformation assay, dominant-negative epistasis, JNK assay The Journal of biological chemistry High 10744696
2001 CDC42 and Rac1 activation leads to phosphorylation of the NF2 tumor suppressor merlin at serine 518 via PAK; both in vivo and in vitro PAK kinase assays confirm direct phosphorylation of merlin at this site, which affects merlin's activity and localization. In vivo and in vitro kinase assays, dominant-active GTPase expression The Journal of biological chemistry High 11719502
2001 Cdc42Hs promotes neurite outgrowth and cytoskeletal reorganization by localizing the adaptor protein IRS-58 to filamentous actin; IRS-58 binds Cdc42Hs via its CRIB-related domain, and an IRS-58 mutant unable to bind CDC42 fails to localize to F-actin or induce neurite outgrowth. Yeast two-hybrid, immunofluorescence co-localization, mutant overexpression, neurite outgrowth assay The Journal of cell biology Medium 11157984
2002 Rac1 and CDC42 capture microtubules at the cell cortex through a tripartite complex with IQGAP1 and CLIP-170; activated Rac1/Cdc42 recruits IQGAP1, which binds CLIP-170 (a microtubule plus-end protein), leading to polarized microtubule arrays and cell polarization; disruption of IQGAP1-CLIP-170 interaction delocalizes microtubule plus ends. Co-immunoprecipitation, pull-down, GFP imaging, dominant-negative and truncation mutant expression Cell High 12110184
2002 IQGAP1 overexpression increases GTP-bound (active) CDC42 levels and induces actin microspikes; an IQGAP1 mutant lacking part of its GAP-related domain (ΔGRD) increases intrinsic CDC42 GTPase activity in vitro, decreasing active CDC42 and blocking bradykinin-induced filopodia and CDC42 membrane translocation. GTP-CDC42 pull-down, in vitro GTPase assay, dominant-negative mutant, filopodia imaging The Journal of biological chemistry High 11948177
2003 Activated CDC42 binds p85Cool-1/β-Pix, which directly associates with c-Cbl ubiquitin ligase; this complex formation prevents c-Cbl from binding the EGF receptor, thereby inhibiting receptor ubiquitination and degradation; constitutively active CDC42(F28L) causes persistent receptor accumulation and sustained ERK activation leading to transformation. Co-immunoprecipitation, ubiquitination assay, dominant-active mutant, receptor degradation assay Cell High 14505571
2003 A 24 amino acid region within IQGAP1's GRD is necessary and sufficient for CDC42 binding; deletion of this region abolishes IQGAP1-CDC42 binding in vitro and in vivo, prevents IQGAP1 from increasing active CDC42 in cells, and causes IQGAP1 mislocalization to the cell periphery. SPOT analysis, peptide competition, deletion mutant co-IP, active CDC42 pull-down Biochemical and biophysical research communications High 12745076
2000 Three-dimensional NMR solution structure of CDC42Hs·GMPPCP in complex with a 46 amino acid PAK binding domain (PBD46) showed PBD46 forms an intermolecular β-sheet with β2 of CDC42Hs and contacts both switch I and switch II; this interaction reorients α-helix 1 and orders switch regions compared to free CDC42Hs. Heteronuclear NMR, distance geometry, simulated annealing structure calculation Biochemistry High 10747784
2005 Active CDC42 and RhoA form concentric, distinct zones around wound sites in Xenopus oocytes: active CDC42 occupies the mid-zone of the F-actin array and active RhoA the interior; zones form before F-actin accumulation, require microtubules, F-actin, and crosstalk between RhoA and CDC42, and move with the closing actomyosin array. Fluorescence biosensors (GFP-WASP CRIB domain), live imaging, pharmacological inhibitors The Journal of cell biology High 15684032
2005 Ect2 (a Rho GEF) activates CDC42 during metaphase (GTP-CDC42 peaks in metaphase), while MgcRacGAP down-regulates CDC42; this CDC42 activation cycle is required for proper bi-orient attachment of spindle microtubules to kinetochores, and depletion of either regulator causes prometaphase delay and chromosome mis-segregation. Pull-down GTP-CDC42 assay, RNAi, dominant-negative mutants, live-cell imaging The Journal of cell biology High 15642749
2005 Secramine inhibits Cdc42 activation in a RhoGDI-dependent manner: in vitro, secramine prevents Cdc42 binding to membranes, GTP, and effectors only when RhoGDI is present; in cells it mimics dominant-negative CDC42, blocking Golgi protein export and Golgi polarization. In vitro membrane binding assay, GTP binding assay, effector pulldown, dominant-negative phenocopy Nature chemical biology High 16408091
2005 CDC42 inactivation (siRNA knockdown) in dermal fibroblasts causes ~15-fold upregulation of MMP-1 via increased ERK1/2 phosphorylation; Cdc42 normally represses MMP-1 expression through suppression of the Rac1–ERK1/2 pathway, contributing to extracellular matrix homeostasis. siRNA knockdown with rescue, cytokine/MMP ELISAs, RT-PCR, kinase inhibitors Journal of cell science Medium 15728253
2007 PTEN localizes to the apical plasma membrane during epithelial morphogenesis, enriching PtdIns(4,5)P2 there; Annexin 2 binds PtdIns(4,5)P2 and recruits CDC42 to the apical surface; CDC42 then recruits aPKC; loss of PTEN, Anx2, CDC42, or aPKC prevents apical surface and lumen formation. Conditional knockdown, rescue experiments, 3D cyst culture, immunofluorescence localization Cell High 17254974
2008 The N-terminus of exocyst component Sec3 directly interacts with PtdIns(4,5)P2, and key residues in Sec3 are required for binding GTP-bound Cdc42; dual interactions of Sec3 with phospholipids and Cdc42 control exocytosis and polarized cell growth; disrupting either interaction blocks exocytosis and causes morphogenesis defects in yeast. Lipid-binding assay, GTP-Cdc42 binding assay, yeast genetics, cell morphology The Journal of cell biology High 18195105
2008 Cdc42 cooperates with the neuronal F-BAR/SH3 protein Nervous Wreck (Nwk) to promote WASp-mediated actin polymerization at Rab11-positive recycling endosomes, thereby regulating synaptic growth at the Drosophila NMJ; Nwk interacts with dynamin and Dap160 in this endocytic complex. Genetic epistasis in Drosophila, in vitro actin polymerization assay, co-IP The Journal of neuroscience Medium 18701694
2009 Cdc42 is essential for pancreatic tubulogenesis: it is required for initiating microlumen formation and maintaining apical cell polarity; Cdc42 controls cell specification non-cell-autonomously by providing the correct microenvironment for multipotent progenitor fate choices. Conditional Cdc42 knockout mice, live imaging, immunofluorescence Cell High 19914171
2010 During directed cell migration, CDC42 accumulates at the leading edge through Arf6-dependent membrane trafficking of CDC42-positive intracytoplasmic vesicles; inhibition of Arf6-dependent trafficking abolishes polarized recruitment of CDC42 and its exchange factor βPIX, preventing cell polarization. Live-cell imaging of GFP-CDC42, Arf6 dominant-negative, immunofluorescence The Journal of cell biology High 21173111
2013 Septins recruited to the polarity site by CDC42-GTP inhibit CDC42 activity in a negative feedback loop requiring CDC42 GAPs; polarized exocytosis sculpts the septin ring to relieve CDC42 inhibition; the nascent septin ring then confines CDC42 activity strictly within the bud, establishing daughter cell identity. Live-cell imaging, computational modeling, conditional mutant analysis in budding yeast Developmental cell High 23906065
2013 Tissue-specific inactivation of Cdc42 in kidney nephrogenic lineage causes severe nephrogenesis defects that phenocopy loss of Yap; Cdc42 loss decreases nuclear localization of Yap and reduces Yap-dependent gene expression, placing CDC42 upstream of Yap in a pathway controlling nephron morphogenesis. Conditional knockout mouse, immunofluorescence, microarray gene expression PLoS genetics High 23555292
2013 Cdc42 co-localizes with the exocyst component Sec10 at primary cilia; cdc42 knockdown in zebrafish phenocopies sec10 knockdown (tail curvature, glomerular expansion, MAPK activation, loss of photoreceptor cilia); synergistic genetic interaction between cdc42 and sec10 suggests they act in the same ciliogenesis pathway. Zebrafish morpholino knockdown, genetic interaction, conditional mouse kidney KO, histology Journal of the American Society of Nephrology High 23766535
2013 During mitotic exit, CDC42 must be downregulated for cytokinesis; Cdc5/Polo kinase suppresses CDC42 activity; failure to inhibit CDC42 during mitotic exit impairs localization of cytokinesis regulators Iqg1 and Inn1 at the division site via the CDC42 effector PAK Ste20, causing abnormal septum formation. Biochemical CDC42 activity assay, live imaging, genetic epistasis, polo kinase analog-sensitive allele The Journal of cell biology High 23878274
2013 A CDC42-selective allosteric inhibitor (non-competitive, acting via RhoGDI) was characterized; it shows no inhibition of Rho or Rac; in cells it inhibits CDC42-dependent filopodia formation, cell migration, Sin Nombre virus internalization, and VLA-4 integrin signaling. GTPase biochemical assay, structure-activity relationship, cellular filopodia and migration assays The Journal of biological chemistry High 23382385
2015 Local CDC42 signals (but not Rac, RhoA, or Ras) precede cell turning during chemotaxis in neutrophil-like PLB-985 cells; pre-existing local CDC42 activity in unpolarized cells predicts the future direction of movement; CDC42 antagonizes RhoA globally and maintains a steep spatial activity gradient, with excitable CDC42 signals acting as a compass for steering. FRET biosensors, photorelease of chemoattractant, pharmacological actin depolymerization Nature cell biology High 26689677
2016 Crystal structure of CDC42·GTP bound to the GRD of IQGAP2 revealed two distinct Cdc42-binding sites per GRD dimer: two CDC42 molecules bind analogously to Ras/RasGAP interactions while two others bind extra-domain sequences, promoting IQGAP dimerization; calorimetry confirmed two-site binding for both IQGAP1 and IQGAP2 GRDs; Rac1·GTP shows only single-site binding, meaning only CDC42 promotes IQGAP dimerization. X-ray crystallography, isothermal titration calorimetry, mutagenesis Structure High 27524202
2017 Optogenetics combined with micropatterning showed that CDC42 gradients are set by spatial patterns of GEFs (CDC42 distribution follows its GEF), while Rac1 gradient shaping additionally requires the GAP β2-chimaerin, which is localized at the cell tip through feedbacks from CDC42 and Rac1; a sharp CDC42 gradient maximizes migration directionality. Optogenetics, micropatterning, FRET biosensors, GAP perturbation Nature communications High 30446664
2017 Cytoplasmic YAP positively regulates CDC42 activity in vascular endothelial cells; deletion of CDC42 causes severe endothelial migration defects phenocopying YAP/TAZ loss; nuclear YAP blocks endothelial migration and phenocopies CDC42 deficiency, establishing a YAP–CDC42 axis in vascular tip cell migration. Conditional knockout mice, retinal angiogenesis imaging, active CDC42 pull-down Proceedings of the National Academy of Sciences of the United States of America High 28973878
2017 The scaffold Bem1 directly stimulates the GEF activity of Cdc24 toward Cdc42; Bem1 also promotes Cdc24 phosphorylation by PAK (Cla4), which abrogates scaffold-dependent GEF stimulation; this creates a self-regulatory feedback loop controlling CDC42 activation flux at polarity sites. In vitro GEF assay with purified proteins, phosphorylation assay, live imaging of active CDC42 eLife High 28304276
2018 Single-particle tracking (sptPALM) in budding yeast showed Cdc42 forms nanoclusters at the cell pole with reduced mobility; GTP-bound Cdc42 has larger nanoclusters; the scaffold Bem1 regulates nanocluster size and Cdc42 mobility; phosphatidylserine levels regulate Cdc42 nanoclustering, countering dissipative diffusion to sustain polarity. sptPALM, CRISPR-based GFP tagging, lipid mutants Molecular biology of the cell High 29668348
2018 Missense variants in CDC42 that variably alter the switch between active/inactive GTP states and/or CDC42-effector interactions cause a clinically heterogeneous developmental syndrome; in vitro GTPase assays, effector binding assays, and zebrafish/cell models show mutations differentially impair function. In vitro GTPase assays, effector binding (in vitro), zebrafish in vivo modeling American journal of human genetics High 29394990
2019 Endothelial-specific postnatal deletion of CDC42 in mice causes cerebrovascular malformations resembling cerebral cavernous malformations (CCMs); mechanistically, CDC42 loss increases MEKK3–MEK5–ERK5 signaling and KLF2/KLF4 expression; genetic co-inactivation of Klf4 reduces malformation severity; CDC42 interacts with CCM proteins and CCM3 promotes CDC42 activity. Inducible endothelial-specific KO mouse, co-immunoprecipitation, genetic epistasis, signaling pathway analysis Circulation research High 30732528
2022 pTINCR, a microprotein encoded by the TINCR lncRNA, binds CDC42 and promotes its SUMOylation; increased CDC42 SUMOylation activates CDC42, triggering a pro-differentiation cascade in epithelial cells; pTINCR SIM-domain mutants unable to interact with SUMO are unable to activate CDC42 or promote differentiation. Co-immunoprecipitation, SUMOylation assay, gain/loss-of-function, patient-derived xenografts Nature communications Medium 36369429
2001 Signal transduction in Slit-Robo neuronal migration involves Cdc42 inactivation: the intracellular domain of Robo recruits srGAP1, which inactivates Cdc42; dominant-negative srGAP1 blocks Slit-induced Cdc42 inactivation and Slit repulsion; constitutively active Cdc42 blocks Slit repulsion, placing Cdc42 downstream of Robo/srGAP in migration guidance. Co-immunoprecipitation, dominant-negative epistasis, Cdc42 activity assay, neuronal migration assay Cell High 11672528
2007 FMNL2 and FMNL3 formins localize at the Golgi through N-terminal myristoylation and interaction with CDC42; CDC42-dependent Golgi targeting of FMNL2/3 induces an actin meshwork around the Golgi; loss of FMNL2/3 causes Golgi fragmentation and defective anterograde trafficking of VSV-G, linking CDC42 to actin-dependent vesicle transport at the Golgi. Co-immunoprecipitation, CRISPR/Cas9 knockout, RNAi, VSV-G trafficking assay, immunofluorescence Scientific reports High 28852060
2023 Fasting activates mTORC2, which phosphorylates NDRG1 at Ser336; phospho-NDRG1 engages with mitochondria and cooperates with CDC42 and its effectors/regulators to orchestrate mitochondrial fission; Cdc42-deficient cells display mitochondrial fission failure similar to NDRG1Ser336Ala and RictorKO cells. Time-lapse imaging, siRNA screen, epistasis experiments, proteomics, phospho-mutant analysis Nature cell biology Medium 37386153
1990 G25K (CDC42) undergoes post-translational modification by isoprenoids (mevalonate-derived); isoprenylation promotes membrane association of CDC42, as inhibition of isoprenoid synthesis by lovastatin shifts CDC42 from particulate to soluble fractions and alters its electrophoretic mobility. [3H]mevalonate labeling, 2D electrophoresis, lovastatin treatment, subcellular fractionation The Journal of biological chemistry High 2120220
1992 G25K (CDC42) is carboxyl-methylated in brain in a GTP-stimulated manner (GTPγS decreases Km 4.6-fold); methylation correlates with membrane association; soluble CDC42 exists as a heterodimer with a 28 kDa protein that decreases methylation efficiency, suggesting GDI regulates post-translational modification. Protein purification, methyltransferase assay, subcellular fractionation The Journal of biological chemistry Medium 1526984

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Towards a proteome-scale map of the human protein-protein interaction network. Nature 2090 16189514
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
1995 Selective activation of the JNK signaling cascade and c-Jun transcriptional activity by the small GTPases Rac and Cdc42Hs. Cell 1457 7600582
1994 A brain serine/threonine protein kinase activated by Cdc42 and Rac1. Nature 1377 8107774
2006 A germline-specific class of small RNAs binds mammalian Piwi proteins. Nature 1362 16751776
1995 The Rho family GTPases RhoA, Rac1, and CDC42Hs regulate transcriptional activation by SRF. Cell 1197 7600583
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2000 The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42. Nature cell biology 761 10934474
1996 Wiskott-Aldrich syndrome protein, a novel effector for the GTPase CDC42Hs, is implicated in actin polymerization. Cell 734 8625410
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2002 Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck. Nature 666 12181570
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2000 Autoinhibition and activation mechanisms of the Wiskott-Aldrich syndrome protein. Nature 621 10724160
2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
2007 PTEN-mediated apical segregation of phosphoinositides controls epithelial morphogenesis through Cdc42. Cell 586 17254974
1998 Induction of filopodium formation by a WASP-related actin-depolymerizing protein N-WASP. Nature 568 9422512
2003 Divergent signals and cytoskeletal assemblies regulate self-organizing polarity in neutrophils. Cell 563 12887922
2005 High-throughput mapping of a dynamic signaling network in mammalian cells. Science (New York, N.Y.) 553 15761153
1995 A conserved binding motif defines numerous candidate target proteins for both Cdc42 and Rac GTPases. The Journal of biological chemistry 552 7493928
1997 Bni1p, a yeast formin linking cdc42p and the actin cytoskeleton during polarized morphogenesis. Science (New York, N.Y.) 540 9082982
1998 Activation of Rac and Cdc42 by integrins mediates cell spreading. Molecular biology of the cell 536 9658176
2017 Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science (New York, N.Y.) 533 28302793
2002 Rac1 and Cdc42 capture microtubules through IQGAP1 and CLIP-170. Cell 502 12110184
2011 Analysis of the myosin-II-responsive focal adhesion proteome reveals a role for β-Pix in negative regulation of focal adhesion maturation. Nature cell biology 490 21423176
2001 Signal transduction in neuronal migration: roles of GTPase activating proteins and the small GTPase Cdc42 in the Slit-Robo pathway. Cell 466 11672528
2000 IRSp53 is an essential intermediate between Rac and WAVE in the regulation of membrane ruffling. Nature 454 11130076
1997 Regulation of dendritic growth and remodeling by Rho, Rac, and Cdc42. Neuron 441 9331353
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
1998 A role for Cdc42 in macrophage chemotaxis. The Journal of cell biology 436 9606207
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2001 Rho and Rac but not Cdc42 regulate endothelial cell permeability. Journal of cell science 391 11257000
1994 Activation of phosphoinositide 3-kinase activity by Cdc42Hs binding to p85. The Journal of biological chemistry 346 8034624
1996 IQGAP1, a calmodulin-binding protein with a rasGAP-related domain, is a potential effector for cdc42Hs. The EMBO journal 342 8670801
1997 Requirements for both Rac1 and Cdc42 in membrane ruffling and phagocytosis in leukocytes. The Journal of experimental medicine 341 9348306
1995 A novel serine kinase activated by rac1/CDC42Hs-dependent autophosphorylation is related to PAK65 and STE20. The EMBO journal 327 7744004
1998 PAK4, a novel effector for Cdc42Hs, is implicated in the reorganization of the actin cytoskeleton and in the formation of filopodia. The EMBO journal 309 9822598
2005 Concentric zones of active RhoA and Cdc42 around single cell wounds. The Journal of cell biology 278 15684032
2013 Yap- and Cdc42-dependent nephrogenesis and morphogenesis during mouse kidney development. PLoS genetics 250 23555292
2000 Vav2 is an activator of Cdc42, Rac1, and RhoA. The Journal of biological chemistry 227 10744696
2001 p21-activated kinase links Rac/Cdc42 signaling to merlin. The Journal of biological chemistry 218 11719502
2008 Membrane association and functional regulation of Sec3 by phospholipids and Cdc42. The Journal of cell biology 206 18195105
2009 Cdc42-mediated tubulogenesis controls cell specification. Cell 202 19914171
2018 Targeting Rac and Cdc42 GTPases in Cancer. Cancer research 201 29858187
1998 Fc receptor-mediated phagocytosis requires CDC42 and Rac1. The EMBO journal 196 9799231
1997 A novel Cdc42Hs mutant induces cellular transformation. Current biology : CB 194 9368762
2011 Cdc42 in oncogenic transformation, invasion, and tumorigenesis. Cellular signalling 193 21515363
2003 Activated Cdc42 sequesters c-Cbl and prevents EGF receptor degradation. Cell 167 14505571
1998 The p21Rac/Cdc42-activated kinases (PAKs). The international journal of biochemistry & cell biology 167 9744077
1997 Cdc42Hs, but not Rac1, inhibits serum-stimulated cell cycle progression at G1/S through a mechanism requiring p38/RK. The Journal of biological chemistry 167 9148940
2017 YAP/TAZ-CDC42 signaling regulates vascular tip cell migration. Proceedings of the National Academy of Sciences of the United States of America 162 28973878
1992 The identification and characterization of a GDP-dissociation inhibitor (GDI) for the CDC42Hs protein. The Journal of biological chemistry 153 1429634
2018 Functional Dysregulation of CDC42 Causes Diverse Developmental Phenotypes. American journal of human genetics 152 29394990
2010 Signaling role of Cdc42 in regulating mammalian physiology. The Journal of biological chemistry 144 21115489
2010 Cdc42 localization and cell polarity depend on membrane traffic. The Journal of cell biology 143 21173111
2001 Cdc42Hs facilitates cytoskeletal reorganization and neurite outgrowth by localizing the 58-kD insulin receptor substrate to filamentous actin. The Journal of cell biology 139 11157984
2015 Locally excitable Cdc42 signals steer cells during chemotaxis. Nature cell biology 138 26689677
2002 IQGAP1 is a component of Cdc42 signaling to the cytoskeleton. The Journal of biological chemistry 135 11948177
1998 RhoG GTPase controls a pathway that independently activates Rac1 and Cdc42Hs. Molecular biology of the cell 135 9614181
2013 Characterization of a Cdc42 protein inhibitor and its use as a molecular probe. The Journal of biological chemistry 134 23382385
2013 Daughter cell identity emerges from the interplay of Cdc42, septins, and exocytosis. Developmental cell 125 23906065
2005 Secramine inhibits Cdc42-dependent functions in cells and Cdc42 activation in vitro. Nature chemical biology 123 16408091
2003 IQGAP1 as signal integrator: Ca2+, calmodulin, Cdc42 and the cytoskeleton. FEBS letters 115 12729888
1996 Characterization of the interaction between RhoGDI and Cdc42Hs using fluorescence spectroscopy. The Journal of biological chemistry 106 8626553
1998 Chp, a homologue of the GTPase Cdc42Hs, activates the JNK pathway and is implicated in reorganizing the actin cytoskeleton. Current biology : CB 102 9778532
2000 Critical activities of Rac1 and Cdc42Hs in skeletal myogenesis: antagonistic effects of JNK and p38 pathways. Molecular biology of the cell 99 10930450
1998 Stimulation of phospholipase C-beta2 by the Rho GTPases Cdc42Hs and Rac1. The EMBO journal 99 9799233
2002 GTPase-activating proteins for Cdc42. Eukaryotic cell 97 12455995
2008 Nervous wreck and Cdc42 cooperate to regulate endocytic actin assembly during synaptic growth. The Journal of neuroscience : the official journal of the Society for Neuroscience 94 18701694
2005 Ect2 and MgcRacGAP regulate the activation and function of Cdc42 in mitosis. The Journal of cell biology 93 15642749
2020 Targeting Rac and Cdc42 GEFs in Metastatic Cancer. Frontiers in cell and developmental biology 90 32322580
2005 Rac1/Cdc42 and RhoA GTPases antagonistically regulate chondrocyte proliferation, hypertrophy, and apoptosis. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 90 15883643
1997 The small GTPases Cdc42Hs, Rac1 and RhoG delineate Raf-independent pathways that cooperate to transform NIH3T3 cells. Current biology : CB 89 9285711
2019 Regulation of Cdc42 and its effectors in epithelial morphogenesis. Journal of cell science 83 31113848
1994 Investigation of the GTP-binding/GTPase cycle of Cdc42Hs using fluorescence spectroscopy. Biochemistry 72 7918454
2009 IQGAP1 regulates cell proliferation through a novel CDC42-mTOR pathway. Journal of cell science 70 19454477
2013 Cdc42 deficiency causes ciliary abnormalities and cystic kidneys. Journal of the American Society of Nephrology : JASN 69 23766535
1999 Signalling to actin: the Cdc42-N-WASP-Arp2/3 connection. Chemistry & biology 69 10467124
1990 Isoprenoid modification of G25K (Gp), a low molecular mass GTP-binding protein distinct from p21ras. The Journal of biological chemistry 68 2120220
2009 Involvement of Rac/Cdc42/PAK pathway in cytoskeletal rearrangements. Acta biochimica Polonica 66 19513348
1991 Identification of the human platelet GTPase activating protein for the CDC42Hs protein. The Journal of biological chemistry 62 1939135
2013 Inhibition of Cdc42 during mitotic exit is required for cytokinesis. The Journal of cell biology 61 23878274
2018 Optogenetic dissection of Rac1 and Cdc42 gradient shaping. Nature communications 60 30446664
2006 Rac1 and Cdc42 have different roles in Candida albicans development. Eukaryotic cell 57 16467473
2005 Cdc42 downregulates MMP-1 expression by inhibiting the ERK1/2 pathway. Journal of cell science 57 15728253
2004 AKAP350 interaction with cdc42 interacting protein 4 at the Golgi apparatus. Molecular biology of the cell 57 15047863
2015 miR-30c Mediates Upregulation of Cdc42 and Pak1 in Diabetic Cardiomyopathy. Cardiovascular therapeutics 56 25781190
1999 Syndecan-2 induces filopodia by active cdc42Hs. Experimental cell research 56 10222136
2007 The IQGAP1-Rac1 and IQGAP1-Cdc42 interactions: interfaces differ between the complexes. The Journal of biological chemistry 55 17984089
1998 CDC42 and FGD1 cause distinct signaling and transforming activities. Molecular and cellular biology 55 9671479
2004 Regulation of anoikis by Cdc42 and Rac1. Experimental cell research 54 15093747
2006 Ack1 mediates Cdc42-dependent cell migration and signaling to p130Cas. The Journal of biological chemistry 53 17038317
2017 Polarity establishment by Cdc42: Key roles for positive feedback and differential mobility. Small GTPases 51 28350208
1989 Characterization of G25K, a GTP-binding protein containing a novel putative nucleotide binding domain. Biochemical and biophysical research communications 51 2496687
1997 Interaction between Cdc42Hs and RhoGDI is mediated through the Rho insert region. The Journal of biological chemistry 47 9334181
1995 Integrin alpha IIb beta 3-mediated translocation of CDC42Hs to the cytoskeleton in stimulated human platelets. The Journal of biological chemistry 46 7542236
2003 Identification and characterization of the Cdc42-binding site of IQGAP1. Biochemical and biophysical research communications 45 12745076
2019 CDC42 Deletion Elicits Cerebral Vascular Malformations via Increased MEKK3-Dependent KLF4 Expression. Circulation research 44 30732528
2016 The Borg family of Cdc42 effector proteins Cdc42EP1-5. Biochemical Society transactions 43 27913681
1993 Identification of a novel protein with GDP dissociation inhibitor activity for the ras-like proteins CDC42Hs and rac I. Genes, chromosomes & cancer 43 7512369
2012 hnRNP Q regulates Cdc42-mediated neuronal morphogenesis. Molecular and cellular biology 42 22493061
2021 Progress in the therapeutic inhibition of Cdc42 signalling. Biochemical Society transactions 40 34100887
2015 Distinct predictive performance of Rac1 and Cdc42 in cell migration. Scientific reports 40 26634649
1992 GTP-stimulated carboxyl methylation of a soluble form of the GTP-binding protein G25K in brain. The Journal of biological chemistry 40 1526984
2022 pTINCR microprotein promotes epithelial differentiation and suppresses tumor growth through CDC42 SUMOylation and activation. Nature communications 39 36369429
2016 A role for activated Cdc42 in glioblastoma multiforme invasion. Oncotarget 39 27486972
2014 MicroRNA-224 suppresses colorectal cancer cell migration by targeting Cdc42. Disease markers 39 24817781
2023 mTORC2-NDRG1-CDC42 axis couples fasting to mitochondrial fission. Nature cell biology 38 37386153
2016 Cdc42 in actin dynamics: An ordered pathway governed by complex equilibria and directional effector handover. Small GTPases 38 27715449
2020 Regulation of Cdc42 for polarized growth in budding yeast. Microbial cell (Graz, Austria) 37 32656257
1999 MSE55, a Cdc42 effector protein, induces long cellular extensions in fibroblasts. Proceedings of the National Academy of Sciences of the United States of America 37 10430899
2014 Cdc42 and Tks5: a minimal and universal molecular signature for functional invadosomes. Cell adhesion & migration 36 24840388
2000 Structure of the complex of Cdc42Hs with a peptide derived from P-21 activated kinase. Biochemistry 36 10747784
1997 Use of a fluorescence spectroscopic readout to characterize the interactions of Cdc42Hs with its target/effector, mPAK-3. Biochemistry 36 9033409
2018 Phosphatidylserine and GTPase activation control Cdc42 nanoclustering to counter dissipative diffusion. Molecular biology of the cell 35 29668348
2016 The Structural Basis for Cdc42-Induced Dimerization of IQGAPs. Structure (London, England : 1993) 35 27524202
2007 Co-operative Cdc42 and Rho signalling mediates ephrinB-triggered endothelial cell retraction. The Biochemical journal 35 17300218
2000 Extinction of rac1 and Cdc42Hs signalling defines a novel p53-dependent apoptotic pathway. Oncogene 35 10828879
2000 Cell polarity: new PARtners for Cdc42 and Rac. Nature cell biology 35 10934484
2017 Scaffold-mediated gating of Cdc42 signalling flux. eLife 33 28304276
2015 Essential roles of Cdc42 and MAPK in cadmium-induced apoptosis in Litopenaeus vannamei. Aquatic toxicology (Amsterdam, Netherlands) 33 25863597
2014 CDC-42 and RAC-1 regulate opposite chemotropisms in Neurospora crassa. Journal of cell science 33 24790223
2017 FMNL2 and -3 regulate Golgi architecture and anterograde transport downstream of Cdc42. Scientific reports 32 28852060
2000 SPECs, small binding proteins for Cdc42. The Journal of biological chemistry 32 10816584
1998 Identification of the binding surface on Cdc42Hs for p21-activated kinase. Biochemistry 32 9760238