Affinage

CDC42EP1

Cdc42 effector protein 1 · UniProt Q00587

Length
391 aa
Mass
40.3 kDa
Annotated
2026-04-28
27 papers in source corpus 6 papers cited in narrative 6 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CDC42EP1 (also known as MSE55/Borg5) is a CRIB domain-containing effector of GTP-bound Cdc42 that reorganizes the actin cytoskeleton to regulate cell shape, protrusion formation, and directed migration (PMID:10430899, PMID:29040749). Cdc42 binding through the CRIB domain controls CDC42EP1 subcellular distribution between membrane protrusions and perinuclear patches, thereby directing protrusion formation and migration polarity; loss of CDC42EP1 causes rounding, membrane blebbing, and disrupted focal adhesion alignment in cranial neural crest cells (PMID:29040749). CDC42EP1 reciprocally interacts with septin filaments at the cell center to maintain actin stress fiber stability, contractility, and persistent orientation during directed migration (PMID:36923257). In epithelial monolayers, CDC42EP1 interacts with the myosin IIA rod domain and limits actomyosin contractility and cell–cell adhesion tension, with this interaction modulated by septin availability (PMID:39503295).

Mechanistic history

Synthesis pass · year-by-year structured walk · 5 steps
  1. 1992 Medium

    The initial discovery of CDC42EP1 (MSE55) as a novel secreted protein of bone marrow stroma established its molecular identity but left its signaling function unknown.

    Evidence cDNA cloning, immunoblotting, and Northern blot in bone marrow stromal/endothelial cells

    PMID:1629197

    Open questions at the time
    • No signaling pathway placement
    • Functional role beyond expression in hematopoietic niche unresolved
    • Secreted form has not been functionally characterized in subsequent studies
  2. 1999 High

    Demonstrating that MSE55 binds GTP-Cdc42 via its CRIB domain and that this interaction is required for actin reorganization and protrusion formation established CDC42EP1 as a bona fide Cdc42 effector governing cytoskeletal remodeling.

    Evidence GST pulldown, CRIB domain mutagenesis, dominant-negative Cdc42/Rac epistasis, immunofluorescence, and live-cell microscopy in COS-7 and NIH 3T3 cells

    PMID:10430899

    Open questions at the time
    • Downstream effector mechanism linking CRIB engagement to actin remodeling not defined
    • Relevance in a physiological tissue context not established
  3. 2016 High

    Showing that Cdc42 levels control CDC42EP1 partitioning between membrane protrusions and perinuclear patches, and that loss of CDC42EP1 disrupts directed neural crest migration, connected the Cdc42–CDC42EP1 axis to cell polarity and migration in vivo.

    Evidence Morpholino knockdown in Xenopus cranial neural crest, immunofluorescence, CRIB interaction assay, traction force measurements, live imaging

    PMID:29040749

    Open questions at the time
    • Identity of perinuclear interaction partners unknown
    • Mechanism by which CDC42EP1 organizes focal adhesion alignment not resolved
  4. 2023 Medium

    Revealing a reciprocal interaction between CDC42EP1 and septin filaments that maintains actin stress fiber stability and orientation identified septins as a key structural partner bridging CDC42EP1 to the contractile cytoskeleton during directed migration.

    Evidence Morpholino knockdown, colocalization analysis, live imaging, and genetic epistasis between Cdc42ep1 and septins in neural crest cells

    PMID:36923257

    Open questions at the time
    • Direct biochemical binding interface between CDC42EP1 and septins not mapped
    • Whether septin interaction is CRIB-domain-dependent or -independent is untested
    • Single-lab finding not independently replicated
  5. 2024 Medium

    Identifying myosin IIA (MYH9) rod domain as a direct CDC42EP1-binding partner whose interaction is antagonized by septins provided a molecular mechanism by which CDC42EP1 limits actomyosin contractility in epithelial sheets.

    Evidence Co-immunoprecipitation, mass spectrometry, Borg5 depletion in MDCK monolayers, functional contractility and adhesion assays

    PMID:39503295

    Open questions at the time
    • Structural basis of CDC42EP1–myosin IIA rod interaction unknown
    • How septin competition for CDC42EP1 is spatiotemporally regulated is unresolved
    • Single-lab finding; reciprocal validation performed but independent replication pending

Open questions

Synthesis pass · forward-looking unresolved questions
  • A unified structural and regulatory model explaining how Cdc42, septins, and myosin IIA compete for CDC42EP1 binding to coordinate protrusion, polarity, and contractility remains to be established.
  • No high-resolution structural data for CDC42EP1 or its complexes
  • Relative binding affinities among Cdc42, septins, and myosin IIA not quantified
  • In vivo relevance in mammalian tissues beyond neural crest and epithelia not tested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 4
Localization
GO:0005856 cytoskeleton 3 GO:0005886 plasma membrane 1
Pathway
R-HSA-162582 Signal Transduction 2
Partners
CDC42MYH9

Evidence

Reading pass · 6 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 CDC42EP1 (MSE55) was identified as a novel secreted protein expressed specifically in bone marrow stromal and endothelial cells, with a circulating serum form of ~55 kDa, suggesting a functional role in hematopoiesis. cDNA cloning, immunoblotting, Northern blot analysis, recombinant protein expression in E. coli The Journal of biological chemistry Medium 1629197
1999 CDC42EP1 (MSE55) binds to Cdc42 in a GTP-dependent manner through its CRIB domain; this interaction is required for MSE55-induced actin cytoskeleton reorganization, including membrane ruffle formation in COS-7 cells and long actin-based protrusions in NIH 3T3 cells. MSE55-induced protrusion formation was blocked by dominant-negative N17Cdc42 but not by dominant-negative N17Rac, placing MSE55 downstream of Cdc42 specifically. GST pulldown, CRIB domain mutagenesis, dominant-negative Cdc42/Rac overexpression, immunofluorescence, live-cell video microscopy Proceedings of the National Academy of Sciences of the United States of America High 10430899
2016 CDC42EP1 is required for directed migration of cranial neural crest cells; loss of Cdc42ep1 leads to rounder cell shapes, membrane blebbing, disrupted actin organization, and loss of focal adhesion alignment. Cdc42 directly interacts with Cdc42ep1 via the CRIB domain and regulates its subcellular localization: Cdc42ep1 is found in membrane protrusions (together with Cdc42) and in perinuclear patches (where Cdc42 is absent), and changes in Cdc42 level shift Cdc42ep1 distribution between these locations to control protrusion formation and migration directionality. Morpholino-mediated knockdown in Xenopus embryos, immunofluorescence, CRIB domain interaction assay, traction force measurements, live imaging Journal of molecular cell biology High 29040749
2023 Cdc42ep1 colocalizes with septin filaments at the cell center in neural crest cells and interacts with septins in a reciprocal manner: septin filaments recruit Cdc42ep1 to the cell center, and Cdc42ep1 supports the formation of septin filaments. This Cdc42ep1–septin interaction is required for the stability, contractility, and persistent orientation of actin stress fibers during directed cell migration. Morpholino knockdown, colocalization analysis, live imaging, genetic epistasis between Cdc42ep1 and septin Frontiers in cell and developmental biology Medium 36923257
2024 Epithelial Borg5/Cdc42EP1 limits actomyosin contractility, cell-cell adhesion tension, and motility in MDCK monolayers; Borg5 depletion inhibits lateral F-actin cortex development and stimulates radial stress fibers. Borg5 interacts with the rod domain of myosin IIA (MYH9 heavy chain), and this interaction is reduced in the presence of septins. Borg5 also limits septin colocalization with microtubules, suggesting that Borg5 restricts contractility partly by counteracting septin-associated myosin activity. Borg5 depletion (KD) in MDCK cells, co-immunoprecipitation with myosin IIA rod domain, immunofluorescence, mass spectrometry (Überheide), functional contractility assays Journal of cell science Medium 39503295
2023 CDC42EP1 expression is upregulated in ectopic endometriosis lesions and acts downstream of hsa_circ_0005991 via sponging of miR-30b-3p; elevated CDC42EP1 promotes epithelial-mesenchymal transition (EMT), and proliferation, migration, and invasion in Ishikawa cells. CircRNA/miRNA overexpression and knockdown, co-transfection rescue experiments, Western blot for EMT markers, cell function assays Genomics Low 37757976

Source papers

Stage 0 corpus · 27 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 The peptide-encoding CEP1 gene modulates lateral root and nodule numbers in Medicago truncatula. Journal of experimental botany 167 24259455
2014 The cysteine protease CEP1, a key executor involved in tapetal programmed cell death, regulates pollen development in Arabidopsis. The Plant cell 163 25035401
2007 Reduced expression of the Caenorhabditis elegans p53 ortholog cep-1 results in increased longevity. The journals of gerontology. Series A, Biological sciences and medical sciences 65 17895432
2014 CEP-1, the Caenorhabditis elegans p53 homolog, mediates opposing longevity outcomes in mitochondrial electron transport chain mutants. PLoS genetics 53 24586177
2004 Structural differences in the DNA binding domains of human p53 and its C. elegans ortholog Cep-1. Structure (London, England : 1993) 48 15242600
2023 The small peptide CEP1 and the NIN-like protein NLP1 regulate NRT2.1 to mediate root nodule formation across nitrate concentrations. The Plant cell 43 36440970
2016 The Borg family of Cdc42 effector proteins Cdc42EP1-5. Biochemical Society transactions 43 27913681
1998 Mutations synthetically lethal with cep1 target S. cerevisiae kinetochore components. Genetics 42 9584087
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
2019 The papain-like cysteine protease CEP1 is involved in programmed cell death and secondary wall thickening during xylem development in Arabidopsis. Journal of experimental botany 35 30376110
2022 Application of Synthetic Peptide CEP1 Increases Nutrient Uptake Rates Along Plant Roots. Frontiers in plant science 23 35046980
2016 The p53-like Protein CEP-1 Is Required for Meiotic Fidelity in C. elegans. Current biology : CB 23 27151662
2006 A biphenotypic transformation of 8p11 myeloproliferative syndrome with CEP1/FGFR1 fusion gene. European journal of haematology 23 16879608
1992 cDNA cloning and molecular characterization of MSE55, a novel human serum constituent protein that displays bone marrow stromal/endothelial cell-specific expression. The Journal of biological chemistry 23 1629197
2010 A role for borg5 during trophectoderm differentiation. Stem cells (Dayton, Ohio) 22 20506138
2018 Cdc42 regulates the cellular localization of Cdc42ep1 in controlling neural crest cell migration. Journal of molecular cell biology 15 29040749
2019 γVPE plays an important role in programmed cell death for xylem fiber cells by activating protease CEP1 maturation in Arabidopsis thaliana. International journal of biological macromolecules 13 31279878
2023 Coordinated regulation of Cdc42ep1, actin, and septin filaments during neural crest cell migration. Frontiers in cell and developmental biology 4 36923257
2023 hsa_circ_0005991 promotes epithelial-mesenchymal transition by regulating miR-30b-3p/Cdc42EP1 axis in ovary endometriosis. Genomics 3 37757976
2022 cep-1 mediated the mitohormesis effect of Shengmai formula in regulating Caenorhabditis elegans lifespan. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 3 35687906
2025 Nitrate starvation inhibits stomatal opening via the long-distance CEP1-CEPR2 signaling cascade. Cell reports 2 41100250
2024 Evaluating the expression pattern of ATXN1 and CDC42EP1 genes and related long noncoding RNAs in oral squamous cell carcinoma. Molecular biology reports 2 39002033
2024 Borg5 restricts contractility and motility in epithelial MDCK cells. Journal of cell science 2 39503295
2025 Protein phosphatase 2A B'α and B'β promote pollen wall construction partially through BRASSINAZOLE-RESISTANT 1-activated cysteine protease gene CEP1 in Arabidopsis. Journal of experimental botany 1 39798077
2024 Novel Chimeric Peptides Based on the Enolase Peptide Antigen (CEP-1) Bearing Three Post-Translational Modifications (Citrullination, Homocitrullination and Acetylation) for Determining the Diagnosis and Severity of Rheumatoid Arthritis. International journal of molecular sciences 1 39408982
2024 Characterization and Comparative Genomic Analysis of vB_BceM_CEP1: A Novel Temperate Bacteriophage Infecting Burkholderia cepacia Complex. Journal of microbiology (Seoul, Korea) 1 39557803
1991 Interaction with CEP-1 beta-lactamase of RU 51746-2, the active form of the new oral cephalosporin RU 51807. Journal of chemotherapy (Florence, Italy) 1 12041786