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Showing CBY1 — CHIBBY is a alias.

CBY1

Protein chibby homolog 1 · UniProt Q9Y3M2

Length
126 aa
Mass
14.5 kDa
Annotated
2026-06-09
66 papers in source corpus 29 papers cited in narrative 29 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

CBY1 (Chibby1) is a conserved, partially disordered coiled-coil protein with dual roles as an antagonist of Wnt/β-catenin signaling and as a structural organizer at the centriole-to-cilium interface (PMID:12712206, PMID:19364920). In the nucleus it directly binds the C-terminal activation domain of β-catenin and represses β-catenin/Tcf-Lef-driven transcription by competing with Lef-1 for β-catenin binding (PMID:12712206). This repressive output is tuned by partners that bind CBY1 to relieve or redirect its activity, and by Akt-mediated phosphorylation of serine 20, which creates a 14-3-3 docking site; 14-3-3 binding assembles a tripartite CBY1–β-catenin complex, biases CBY1 toward CRM1-dependent nuclear export over importin-α import, and drives cytoplasmic sequestration of both proteins (PMID:18573912, PMID:19940019, PMID:25909186). Structurally, CBY1 comprises a disordered N-terminal half that engages 14-3-3 and a C-terminal coiled-coil that mediates homodimerization and binds the disordered partner TC-1, with dimerization required for efficient nuclear import (PMID:19435523, PMID:21182262, PMID:27082063). At the cilium, CBY1 localizes as a ring at the distal end of the mature mother centriole, recruited there via CEP164 and Cenexin, and drives basal body docking and ciliary vesicle formation by recruiting the Rabin8–Rab8 module (PMID:19364920, PMID:22911743, PMID:25313408, PMID:25103236). Within a DZIP1L/DZIP1-CBY1-FAM92 module at the centriole-to-cilium interface, CBY1 maintains transition zone integrity, recruits Ahi1, and ensures proper IFT-B distribution, with the FAM92A BAR domain binding the CBY1 N-terminus to remodel ciliary membrane (PMID:25103236, PMID:26266958, PMID:27528616, PMID:29487109, PMID:40484380). Loss of CBY1 in mice produces ciliopathy phenotypes including impaired mucociliary airway clearance, cystic kidneys, and exocrine pancreatic degeneration, and biallelic loss-of-function variants in humans cause a Joubert syndrome-spectrum ciliopathy (PMID:19364920, PMID:25103236, PMID:33131181, PMID:34446743).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 2003 High

    Established CBY1's founding molecular function: the unknown was what restrains β-catenin transcriptional output, and CBY1 was shown to directly bind β-catenin's C-terminus and compete with Lef-1 to repress Wnt target genes.

    Evidence Yeast two-hybrid, Co-IP, transcriptional reporter assays, and Drosophila RNAi epistasis

    PMID:12712206

    Open questions at the time
    • Did not resolve how CBY1 is itself regulated
    • Did not address any non-nuclear function
  2. 2004 Medium

    First link to membrane trafficking: CBY1 (PIGEA-14) was shown to bind the polycystin-2 C-terminus and GM130 and redistribute PC2 to the trans-Golgi, hinting at a role beyond transcription.

    Evidence Yeast two-hybrid and co-expression localization in LLC-PK1 and HeLa cells

    PMID:15194699

    Open questions at the time
    • No reciprocal Co-IP or in vitro reconstitution
    • Physiological significance of PC2 trafficking role unestablished
  3. 2006 Medium

    Defined a positive regulator of Wnt acting through CBY1: TC1/C8orf4 binds CBY1 and relieves its antagonism, showing CBY1 repression is a regulatable node.

    Evidence Co-IP, fluorescence colocalization, and TOPflash reporter assays

    PMID:16424001

    Open questions at the time
    • Binding interface not mapped at residue level
    • No in vitro reconstitution
  4. 2007 High

    Connected CBY1's β-catenin antagonism to a developmental output: CBY1 promotes adipocyte differentiation by inhibiting β-catenin signaling.

    Evidence RNAi, overexpression, and adipogenic differentiation assays in 3T3-L1 and ES cells plus Cby-deficient embryo fibroblasts

    PMID:17403895

    Open questions at the time
    • Did not address ciliary functions
    • Mechanism of CBY1 induction during adipogenesis unknown
  5. 2008 High

    Revealed the switch controlling CBY1 compartmentalization: Akt phosphorylates CBY1 at S20, creating a 14-3-3 binding site that assembles a CBY1–14-3-3–β-catenin complex and sequesters β-catenin in the cytoplasm.

    Evidence AP/MS, reciprocal Co-IP, Akt kinase assay, subcellular fractionation, and phosphomutant analysis

    PMID:18573912

    Open questions at the time
    • Did not define the export machinery involved
    • Upstream signals controlling Akt activity in this context not addressed
  6. 2009 High

    Mechanism of compartmentalization resolved: CBY1 shuttles via NLS/NES motifs, and 14-3-3 binding promotes CRM1 association while blocking importin-α, driving CRM1-dependent nuclear export of CBY1 and β-catenin.

    Evidence NLS/NES mutagenesis, leptomycin B treatment, Co-IP with CRM1 and importin-α, shRNA knockdown, and fractionation

    PMID:19940019

    Open questions at the time
    • Quantitative coupling between shuttling rate and β-catenin output not measured
  7. 2009 High

    Defined the structural basis of CBY1 oligomerization: a C-terminal coiled-coil heptad mediates homodimerization, which is dispensable for β-catenin binding/repression but required for importin-α binding and nuclear import.

    Evidence Alanine-scanning mutagenesis, Co-IP, gel filtration, reporter assay, and importin-α binding assay

    PMID:19435523

    Open questions at the time
    • Higher-order assembly state in vivo not determined
  8. 2009 High

    Established CBY1 as a ciliogenesis factor in vivo: CBY1 localizes to the base of cilia, and Cby-/- mice show failed basal body docking, absent mucociliary transport, and motile cilia paucity in airway epithelium.

    Evidence Cby-/- mouse generation, immunofluorescence, electron microscopy, and mucociliary/bacterial clearance assays

    PMID:19364920

    Open questions at the time
    • Molecular recruitment partners at the basal body not yet identified
    • Relationship between ciliary and Wnt roles unresolved
  9. 2012 Medium

    Mapped CBY1 to a specific centriolar substructure and tied it to β-catenin control: Cenexin recruits CBY1 to the distal mother centriole, and this interaction abrogates CBY1's repression of β-catenin transcription.

    Evidence Co-IP, immunofluorescence with centriole appendage markers, and primary cilia assembly assays in quiescent cells

    PMID:22911743

    Open questions at the time
    • Single lab; reciprocal validation limited
    • Direct competition mechanism between centriolar tethering and β-catenin binding not structurally defined
  10. 2012 High

    Tested conservation of CBY1's two roles: Drosophila CBY localizes to the transition zone and is essential for basal body function in sensory neurons and germ cells, but cby mutants show no Wingless defect, indicating the Wnt role may not be conserved.

    Evidence Cby mutant Drosophila analysis, immunofluorescence, EM, and sensory/spermatogenesis assays

    PMID:22508513

    Open questions at the time
    • Why the ciliary role is conserved while the Wnt role diverged unexplained
  11. 2014 High

    Defined the ciliary vesicle pathway: CBY1 is recruited to distal appendages by CEP164 and then engages Rabin8 to recruit Rab8 and assemble ciliary vesicles during basal body docking.

    Evidence Mouse tracheal epithelial cells, Co-IP, immunofluorescence, Cby-/- analysis, EM, and Rabin8/Rab8 recruitment assays

    PMID:25313408

    Open questions at the time
    • Stoichiometry and order of CEP164 vs Cenexin recruitment not fully reconciled
  12. 2014 High

    Resolved CBY1's centriolar architecture and downstream recruitment: super-resolution imaging placed CBY1 in a ~250-nm distal ring downstream of Ofd1, and CBY1 is required to recruit the Joubert protein Ahi1; Cby1-/- mice develop cystic kidneys.

    Evidence 3D-SIM/STED microscopy, Cby1-/- mouse kidney/cilia phenotyping, and Ahi1/Ofd1 localization analysis

    PMID:25103236

    Open questions at the time
    • Mechanism by which CBY1 recruits Ahi1 not defined at the molecular level
  13. 2015 High

    Provided atomic detail of the regulatory switch: the 14-3-3ζ/CBY1 crystal structure confirmed phospho-S20 as essential for recognition, with flanking and noncanonical 14-3-3 loop residues contributing affinity.

    Evidence X-ray crystallography, NMR titration, ITC, and phosphomutant binding analysis

    PMID:25909186

    Open questions at the time
    • Structure of full-length CBY1 or the tripartite β-catenin complex not solved
  14. 2015 High

    Defined CBY1's role in ciliary transport: Cby-/- airway cilia accumulate IFT-B components (IFT88, IFT20, IFT57) but not IFT-A or BBS proteins at dilated tips, establishing a selective IFT-B distribution defect.

    Evidence Cby-/- tracheal epithelial cells, immunofluorescence, TEM, and IFT component co-staining

    PMID:26266958

    Open questions at the time
    • Direct interaction between CBY1 and IFT machinery not demonstrated
  15. 2016 High

    Identified the membrane-remodeling partner: FAM92A/B BAR-domain proteins bind CBY1, depend on it for centriolar localization, and cooperate with CBY1 to generate Rab8-containing membrane structures required for ciliogenesis.

    Evidence Tandem AP/MS, Co-IP, immunofluorescence, Cby1-/- localization analysis, and FAM92A knockdown ciliogenesis assay

    PMID:27528616

    Open questions at the time
    • Lipid specificity and geometry of the membrane-remodeling event addressed only later
  16. 2018 Medium

    Placed CBY1 in an ordered ciliogenesis cascade: Dzip1l binds CBY1 and acts upstream, with Dzip1l loss arresting at ciliary bud formation, CP110 removal failure, and Rpgrip1l recruitment failure.

    Evidence Co-IP, colocalization at basal body appendages, Dzip1l knockout mouse analysis, and epistasis

    PMID:29487109

    Open questions at the time
    • Single lab; biochemical directness of the CBY1–Dzip1l interaction not fully reconstituted
  17. 2016 High

    Dissected the modular binding determinants of CBY1: HDX-MS and truncation analysis showed three structural elements, with TC-1 binding requiring only the coiled-coil and flanking disordered regions modulating affinity.

    Evidence HDX-MS, CD, NMR, ITC, and truncation mutagenesis

    PMID:27082063

    Open questions at the time
    • Functional consequence of disorder-mediated affinity tuning in cells not tested
  18. 2020 High

    Established human disease causation: biallelic loss-of-function CBY1 variants cause a Joubert-spectrum ciliopathy, with patient fibroblasts showing ciliation defects and reduced ciliary AHI1 and ARL13B.

    Evidence Human genetics, patient fibroblast cilia analysis, and zebrafish Cby1 morpholino depletion

    PMID:33131181

    Open questions at the time
    • Genotype-phenotype correlation across the variant spectrum not detailed
  19. 2021 Medium

    Linked the basal body CBY1–β-catenin complex to organ development: DZIP1 stabilizes a DZIP1-CBY1-β-catenin complex at the basal body and restrains β-catenin/MMP2 signaling during cardiac valve development.

    Evidence Co-IP, decoy peptide competition, fractionation, reporter assays, mouse cardiac valve phenotyping, and MVP patient mutation analysis

    PMID:33811421

    Open questions at the time
    • Single lab
    • Whether basal body localization is required for β-catenin restraint not isolated
  20. 2021 High

    Extended the in vivo ciliopathy phenotype to a new organ: Cby1 loss causes exocrine pancreatic atrophy, reduced/short cilia, and defective zymogen granule secretion with altered acinar polarity.

    Evidence Cby1 knockout mouse histology, EM, immunofluorescence, and in vitro acini secretion assay

    PMID:34446743

    Open questions at the time
    • Mechanistic link between ciliary defect and secretory polarity loss unresolved
  21. 2024 High

    Defined cooperative module logic for ciliogenesis initiation: the Cby-Fam92 module and a Cep131-Cep162 module synergistically control basal body Cep290 localization, with concurrent disruption abolishing Cep290 and blocking ciliogenesis.

    Evidence Drosophila genetic double mutants, epistasis, immunofluorescence, EM, and Cep290 localization assays

    PMID:38442096

    Open questions at the time
    • Molecular basis of retroactive interaction between modules not biochemically defined
  22. 2025 High

    Provided structural basis for CBY1-mediated membrane remodeling: the FAM92A BAR domain crystal structure shows a crescent homodimer that binds the CBY1 N-terminus, with synergistic dimerization enhancing affinity and a positively charged concave surface for lipid binding.

    Evidence X-ray crystallography at 2.2 Å, structure-guided mutagenesis, lipid binding, and CBY1 interaction assays

    PMID:40484380

    Open questions at the time
    • Curvature of the membrane shaped in vivo not directly measured
    • How CBY1 dimerization couples to BAR-domain function structurally undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how the nuclear Wnt-antagonist function and the centriolar ciliogenesis function of CBY1 are coordinated within a single cell, and whether the two roles are mechanistically coupled or independent.
  • No study integrates the β-catenin and ciliary functions in one experimental system
  • Whether centriolar tethering is the primary regulator of CBY1's nuclear pool is untested
  • Structure of full-length CBY1 in any complex is unavailable

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0060090 molecular adaptor activity 3 GO:0140110 transcription regulator activity 2
Localization
GO:0005929 cilium 4 GO:0005815 microtubule organizing center 3 GO:0005634 nucleus 2 GO:0005829 cytosol 2 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-1852241 Organelle biogenesis and maintenance 4 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 1
Partners
CEP164CEP290CTNNB1DZIP1LFAM92ARAB8ATC1YWHAE
Complex memberships
CBY1 homodimerCBY1-14-3-3-β-catenin tripartite complexDZIP1-CBY1-FAM92 ciliary module

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 Chibby (CBY1) was identified as a nuclear protein that directly interacts with the C-terminal region of β-catenin and inhibits β-catenin-mediated transcriptional activation by competing with Lef-1 for β-catenin binding. Epistasis experiments in Drosophila indicate chibby acts downstream of wingless and upstream of armadillo. Yeast two-hybrid screen, co-immunoprecipitation, transcriptional reporter assays, Drosophila RNAi epistasis experiments Nature High 12712206
2004 CBY1 (PIGEA-14) interacts with the C-terminus of polycystin-2 (PC2) via yeast two-hybrid, and co-expression of PIGEA-14 with PC2 redistributes both proteins to the trans-Golgi network, suggesting CBY1 regulates intracellular trafficking of polycystin-2. CBY1 also interacts with GM130, a cis-Golgi component, in a two-hybrid screen. Yeast two-hybrid screen, co-expression in LLC-PK1 and HeLa cells, immunofluorescence localization The Journal of biological chemistry Medium 15194699
2008 CBY1 forms a stable tripartite complex with 14-3-3ε/ζ and β-catenin, promoting cytoplasmic sequestration of β-catenin. 14-3-3 specifically recognizes phosphorylated serine 20 of CBY1 (phosphorylated by Akt kinase), and 14-3-3 binding sequesters CBY1 into the cytoplasm. Affinity purification/mass spectrometry, co-immunoprecipitation, Akt kinase assay, subcellular fractionation, phosphomutant analysis The Journal of cell biology High 18573912
2009 CBY1 localizes to the base of cilia, and Cby-knockout mice exhibit impaired basal body docking to the apical surface of multiciliated cells, complete absence of mucociliary transport, and a paucity of motile cilia in nasal epithelium, establishing CBY1 as required for ciliogenesis in airway epithelium. Cby-/- mouse generation, immunofluorescence localization, electron microscopy, mucociliary transport assays, bacterial clearance challenge The Journal of cell biology High 19364920
2009 CBY1 harbors bona fide nuclear localization signal (NLS) and nuclear export signal (NES) motifs and constitutively shuttles between nucleus and cytoplasm. 14-3-3 binding promotes CBY1 interaction with CRM1 nuclear export receptor while inhibiting importin-α binding, driving cytoplasmic compartmentalization of CBY1. NLS/NES-dependent shuttling of CBY1 modulates the dynamic intracellular localization of β-catenin. NLS/NES mutagenesis, shRNA knockdown, nuclear export inhibitor (leptomycin B) treatment, co-immunoprecipitation with CRM1 and importin-α, subcellular fractionation, fluorescence microscopy Molecular biology of the cell High 19940019
2009 CBY1 forms a stable homodimer through a heptad repeat of leucine residues in its C-terminal coiled-coil motif. Alanine substitutions of two or more of four critical leucine residues abolish the CBY1-CBY1 interaction. Dimerization is not required for β-catenin binding or transcriptional repression but is required for efficient interaction with importin-α and subsequent nuclear translocation. Alanine-scanning mutagenesis, co-immunoprecipitation, gel filtration, transcriptional reporter assay, importin-α binding assay BMC molecular biology High 19435523
2006 TC1 (C8orf4) interacts directly with CBY1 and enhances Wnt/β-catenin signaling by relieving CBY1's antagonistic function. Upon co-expression, TC1 redistributes from nucleolus to nuclear speckles where it colocalizes with CBY1. Co-immunoprecipitation, co-localization by fluorescence microscopy, transcriptional reporter assays (TOPflash), gene expression analysis Cancer research Medium 16424001
2007 CBY1 promotes adipocyte differentiation of 3T3-L1 cells by inhibiting β-catenin signaling. CBY1 protein levels increase during adipogenic differentiation and its depletion by RNAi blocks adipogenesis in 3T3-L1 and mouse embryonic stem cells, while ectopic CBY1 expression induces spontaneous adipocyte differentiation. RNAi knockdown, overexpression, adipogenic differentiation assays, β-catenin reporter assay (TOPflash), embryonic fibroblast analysis from Cby-deficient embryos Molecular and cellular biology High 17403895
2007 TC-1 is an intrinsically disordered protein that interacts with CBY1 via three regions of high helical propensity (D44-R53, K58-A64, D73-T88) in its C-terminal portion, as demonstrated by NMR line broadening upon Cby addition. NMR spectroscopy (chemical shift analysis, relaxation measurements), structural characterization of TC-1 Protein science Medium 17905836
2011 Human CBY1 is a partially disordered protein: its N-terminal portion is predominantly unstructured in solution while its C-terminal half forms a coiled-coil structure through self-association. Initial binding studies show the N-terminal unstructured region interacts with 14-3-3ζ while the C-terminal coiled-coil region is involved in TC-1 binding. NMR spectroscopy, ESI-MS, circular dichroism (CD), dynamic light scattering (DLS) Biochemistry Medium 21182262
2012 CBY1 localizes specifically to the distal end of the mother centriole, dependent on recruitment by Cenexin (Cnx). CBY1 physically interacts with Cenexin, and this interaction abrogates CBY1's inhibitory effect on β-catenin-mediated transcription in a dose-dependent manner. CBY1 is dispensable for Cnx localization but required for primary cilia assembly. Co-immunoprecipitation, immunofluorescence localization, centriole appendage marker co-staining, primary cilia assembly assay in quiescent cells PloS one Medium 22911743
2012 Drosophila CBY localizes to the basal body transition zone in sensory neurons and male germ cells and is essential for normal basal body structure and function (sensory transduction and spermatogenesis). Loss of CBY causes altered ciliary trafficking in neuronal cilia and irregular deposition of proteins on spermatocyte basal bodies. Notably, Drosophila cby mutant flies do not show Wingless signaling defects, suggesting the WNT-signaling role may not be conserved in Drosophila. Cby mutant Drosophila analysis, immunofluorescence, electron microscopy, sensory transduction assays, spermatogenesis analysis The Journal of cell biology High 22508513
2014 CBY1 facilitates basal body docking to the apical cell membrane during ciliogenesis by promoting formation of ciliary vesicles at distal appendages. CBY1 is recruited to distal appendages via physical interaction with CEP164. CBY1 then associates with Rabin8 (a GEF for Rab8) to promote Rab8 recruitment and efficient assembly of ciliary vesicles. Primary cultures of mouse tracheal epithelial cells, co-immunoprecipitation, immunofluorescence, Cby-/- mouse analysis, electron microscopy, Rabin8/Rab8 recruitment assays The Journal of cell biology High 25313408
2014 CBY1 localizes to an ~250-nm ring at the distal end of mature centrioles, as revealed by super-resolution microscopy (3D-SIM and STED). CBY1 localization to the distal centriole depends on Ofd1. CBY1 is required for efficient recruitment of Ahi1 (a Joubert syndrome protein/transition zone component) to centrioles; loss of CBY1 reduces centriole-localized Ahi1 but not Ofd1. Deletion of Cby1 results in cystic kidneys and impaired primary cilia formation. Super-resolution microscopy (3D-SIM and STED), Cby1-/- mouse analysis (kidney phenotype, primary cilia), Ahi1/Ofd1 localization analysis in KO cells, cilia recruitment assays Molecular biology of the cell High 25103236
2015 Crystal structure of the human 14-3-3ζ/CBY1 protein-peptide complex reveals a canonical binding mode; phosphorylation of S20 is essential for 14-3-3 recognition, but flanking residues also contribute to binding affinity. NMR titration experiments reveal that residues outside the conserved 14-3-3 binding cleft (flexible loop residues 203-210 of 14-3-3ζ) are also involved in binding CBY1. X-ray crystallography, NMR spectroscopy (backbone resonance assignment, NMR titration), isothermal titration calorimetry (ITC), phosphomutant binding analysis PloS one High 25909186
2015 CBY1 is required for normal ciliary morphology and proper distribution of intraflagellar transport (IFT) particles. In Cby-/- airway cells, IFT88 (IFT-B subcomplex) accumulates in dilated ciliary tips, and IFT-B components (IFT20, IFT57) but not IFT-A or BBS proteins accumulate in distended ciliary tips. Cby-/- mouse and primary tracheal epithelial cell cultures, immunofluorescence, transmission electron microscopy, IFT protein distribution analysis Cell cycle High 26266958
2016 FAM92A and FAM92B (BAR domain-containing proteins) interact with CBY1 as novel binding partners, identified by tandem affinity purification and mass spectrometry. FAM92A colocalizes with CBY1 at centrioles/basal bodies; centriolar localization of FAM92A and FAM92B depends largely on CBY1. FAM92A/B in cooperation with CBY1 induce membrane-remodeling structures containing Rab8, and knockdown of FAM92A impairs ciliogenesis. Tandem affinity purification/mass spectrometry, co-immunoprecipitation, immunofluorescence, Cby1-/- cell localization analysis, FAM92A knockdown ciliogenesis assay Molecular and cellular biology High 27528616
2010 CBY1 interacts with NBPF1 (and other NBPF proteins) through a coiled-coil region in NBPF and the C-terminal coiled-coil domain of CBY1, as shown by yeast two-hybrid and co-immunoprecipitation. CBY1 also interacts with clusterin, and a trimolecular complex of CBY1, NBPF1, and clusterin was co-immunoprecipitated. The NBPF1-CBY1 interaction does not influence CBY1's repressor function in a TOPflash reporter assay. Yeast two-hybrid screening, co-immunoprecipitation, TOPflash reporter assay Experimental cell research Medium 20096688
2013 Phosphorylation of the C-terminal region of polycystin-2 (PC2) at S812 (pseudophosphorylated mutant S812D) reduces its binding affinity to CBY1 (PIGEA14) approximately twofold compared to wild-type PC2, as quantified by quartz crystal microbalance; dissociation constant is in the 10 nM range. Quartz crystal microbalance (QCM) with solid-supported membranes, kinetic binding analysis Biochemical and biophysical research communications Medium 23838289
2016 CBY1 is a partially disordered protein with three structural elements: a disordered N-terminal half, a C-terminal coiled-coil domain, and a C-terminal unstructured extension (~25 residues). TC-1 binding requires only the coiled-coil domain of CBY1; deletion of either disordered region retains TC-1 binding. The C-terminal half of CBY1 alone binds TC-1 with greater affinity than full-length CBY1, suggesting flanking disordered regions modulate target binding. Hydrogen/deuterium exchange mass spectrometry (HDX-MS), circular dichroism, NMR spectroscopy, isothermal titration calorimetry (ITC), truncation mutagenesis Protein science High 27082063
2018 Centrosomal protein Dzip1l interacts with CBY1 (as shown by co-immunoprecipitation), colocalizes at basal body appendages, and acts upstream of CBY1 in ciliogenesis. Loss of Dzip1l arrests ciliogenesis at the stage of ciliary bud formation, with failure to remove capping protein Cp110 from distal centrioles and failure to recruit Rpgrip1l to the transition zone. Co-immunoprecipitation, immunofluorescence co-localization, Dzip1l knockout mouse analysis, epistasis (Dzip1l upstream of Cby1) Development Medium 29487109
2020 Loss-of-function variants in CBY1 in humans cause a ciliopathy with features of Joubert syndrome. Patient fibroblasts show reduced ability to ciliate, increased ciliary length, and reduced levels of ciliary proteins AHI1 and ARL13B. Depletion of Cby1 in zebrafish recapitulates ciliopathy-related phenotypes. Human genetics (biallelic LOF variants), patient fibroblast cilia analysis (immunofluorescence), zebrafish Cby1 depletion morpholino, protein detection by immunofluorescence Human mutation High 33131181
2021 DZIP1 forms a multimeric complex with CBY1 and β-catenin at the basal body of primary cilia. DZIP1 stabilizes the complex and suppresses β-catenin activities. Loss of DZIP1 interaction with CBY1 (via a specific peptide domain) reduces DZIP1 and CBY1 stability and increases β-catenin activities, upregulating MMP2 and causing myxomatous valve phenotype, establishing DZIP1 functions to restrain β-catenin signaling through a CBY1 linker during cardiac development. Co-immunoprecipitation, biochemical decoy peptide experiments, subcellular fractionation, transcriptional reporter assays, mouse cardiac valve phenotype analysis, mutation identification in MVP patients Developmental dynamics Medium 33811421
2021 Loss of Cby1 in mice results in severe exocrine pancreatic atrophy with dilated ducts, reduced cilia number and length in pancreatic tissue, and defective zymogen granule (ZG) secretion with accumulation of ZGs and altered polarity in acinar cells, establishing CBY1 as required for normal ciliogenesis and secretory function in exocrine pancreas. Cby1-knockout mouse analysis, immunofluorescence, histology/electron microscopy, in vitro acini secretion assay Scientific reports High 34446743
2024 The Cby-Fam92 module near the ciliary membrane and the Cep131-Cep162 module near the axoneme synergistically control basal body localization of Cep290 and initiation of ciliogenesis. Concurrent deletion of any protein from both modules causes complete loss of Cep290 from the basal body and blocks ciliogenesis initiation, demonstrating cooperative and retroactive interactions between these complexes. Drosophila genetic double mutants, epistasis analysis, immunofluorescence, electron microscopy, Cep290 localization assays PLoS biology High 38442096
2025 The crystal structure of FAM92A BAR domain (2.2 Å) reveals an antiparallel crescent-shaped homodimer. FAM92A BAR domain directly binds the N-terminal region of CBY1, and dimerization of FAM92A and CBY1 synergistically enhances their binding affinity. Positively charged clusters on the concave BAR surface are critical for lipid binding, and specific residues are essential for dimerization. X-ray crystallography (2.2 Å), structure-guided mutagenesis, lipid binding assays, CBY1 interaction assays The Journal of biological chemistry High 40484380
2026 Rhotekin interacts with CBY1 and competes with β-catenin for binding to CBY1, thereby activating canonical Wnt/β-catenin signaling and promoting osteoblast differentiation. CBY1 suppresses osteoblast differentiation, an effect counteracted by Rhotekin overexpression. Co-immunoprecipitation, competition binding assay, overexpression/knockdown differentiation assays, in vivo bone marrow silencing, β-catenin target gene analysis Cellular signalling Medium 42000008
2013 In BCR-ABL1+ cells, CBY1 enforced expression promotes β-catenin cytoplasmic translocation through its two known mechanisms (Tcf/Lef competition and 14-3-3-mediated nuclear export). Cytoplasmic accumulation of β-catenin activates the unfolded protein response (UPR), leading to induction of BIM and activation of ER-resident caspase-12, contributing to apoptosis. CBY1 overexpression in K562 cells, subcellular fractionation, β-catenin target gene analysis, UPR pathway markers, caspase-12 activation, BIM induction assays Cellular signalling Medium 23707389
2015 CBY1 protein stability in BCR-ABL1+ CML cells is reduced through binding to 14-3-3σ (mediated by Akt phosphorylation of CBY1 at serine 20), leading to proteasome-dependent degradation via enhanced SUMOylation. c-Jun N-terminal kinase (JNK) phosphorylation of 14-3-3σ at serine 186 promotes dissociation of CBY1 from 14-3-3σ, providing a mechanism to modulate CBY1 stability. Co-immunoprecipitation, phosphomutant analysis, proteasome inhibition assays, SUMOylation assays, JNK kinase analysis PloS one Medium 26147002

Source papers

Stage 0 corpus · 66 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Chibby, a nuclear beta-catenin-associated antagonist of the Wnt/Wingless pathway. Nature 233 12712206
2008 Chibby cooperates with 14-3-3 to regulate beta-catenin subcellular distribution and signaling activity. The Journal of cell biology 118 18573912
1983 Major effect on susceptibility to urethan-induced pulmonary adenoma by a single gene in BALB/cBy mice. Journal of the National Cancer Institute 118 6573537
1999 Development and aging of primitive hematopoietic stem cells in BALB/cBy mice. Experimental hematology 88 10340409
2014 Chibby promotes ciliary vesicle formation and basal body docking during airway cell differentiation. The Journal of cell biology 81 25313408
2009 Inactivation of Chibby affects function of motile airway cilia. The Journal of cell biology 79 19364920
2000 Differences between C57BL/6 and BALB/cBy mice in mortality and virus replication after intranasal infection with neuroadapted Sindbis virus. Journal of virology 65 10846099
2012 Drosophila chibby is required for basal body formation and ciliogenesis but not for Wg signaling. The Journal of cell biology 55 22508513
2007 Chibby, an antagonist of the Wnt/beta-catenin pathway, facilitates cardiomyocyte differentiation of murine embryonic stem cells. Circulation 53 17261658
2014 Cby1 promotes Ahi1 recruitment to a ring-shaped domain at the centriole-cilium interface and facilitates proper cilium formation and function. Molecular biology of the cell 52 25103236
2006 TC1 (C8orf4) enhances the Wnt/beta-catenin pathway by relieving antagonistic activity of Chibby. Cancer research 52 16424001
2004 PIGEA-14, a novel coiled-coil protein affecting the intracellular distribution of polycystin-2. The Journal of biological chemistry 52 15194699
2007 Chibby promotes adipocyte differentiation through inhibition of beta-catenin signaling. Molecular and cellular biology 49 17403895
2009 Nuclear-cytoplasmic shuttling of Chibby controls beta-catenin signaling. Molecular biology of the cell 48 19940019
2018 Chibby suppresses aerobic glycolysis and proliferation of nasopharyngeal carcinoma via the Wnt/β-catenin-Lin28/let7-PDK1 cascade. Journal of experimental & clinical cancer research : CR 47 29764469
2016 BAR Domain-Containing FAM92 Proteins Interact with Chibby1 To Facilitate Ciliogenesis. Molecular and cellular biology 43 27528616
2009 Fine-tuning of nuclear-catenin by Chibby and 14-3-3. Cell cycle (Georgetown, Tex.) 37 19158508
1990 Effects of social isolation and the time of day on testosterone levels in plasma of C57BL/6By and BALB/cBy mice. Steroids 35 2326831
2012 A Wnt/beta-catenin pathway antagonist Chibby binds Cenexin at the distal end of mother centrioles and functions in primary cilia formation. PloS one 34 22911743
2008 Real-time quantitative PCR analysis of pediatric ependymomas identifies novel candidate genes including TPR at 1q25 and CHIBBY at 22q12-q13. Genes, chromosomes & cancer 31 18663750
2010 Altered lung morphogenesis, epithelial cell differentiation and mechanics in mice deficient in the Wnt/β-catenin antagonist Chibby. PloS one 30 21049041
2015 Structural Analysis of the 14-3-3ζ/Chibby Interaction Involved in Wnt/β-Catenin Signaling. PloS one 26 25909186
1999 Multidose streptozotocin induction of diabetes in BALB/cBy mice induces a T cell proliferation defect in thymocytes which is reversible by interleukin-4. Cellular immunology 26 10066341
2010 Chibby interacts with NBPF1 and clusterin, two candidate tumor suppressors linked to neuroblastoma. Experimental cell research 24 20096688
2007 The intrinsically disordered TC-1 interacts with Chibby via regions with high helical propensity. Protein science : a publication of the Protein Society 24 17905836
2018 Centrosomal protein Dzip1l binds Cby, promotes ciliary bud formation, and acts redundantly with Bromi to regulate ciliogenesis in the mouse. Development (Cambridge, England) 22 29487109
2006 Reduced expression of beta-catenin inhibitor Chibby in colon carcinoma cell lines. World journal of gastroenterology 22 16570344
2020 Loss of CBY1 results in a ciliopathy characterized by features of Joubert syndrome. Human mutation 20 33131181
2015 Chibby functions to preserve normal ciliary morphology through the regulation of intraflagellar transport in airway ciliated cells. Cell cycle (Georgetown, Tex.) 20 26266958
2011 Structural characterization of partially disordered human Chibby: insights into its function in the Wnt-signaling pathway. Biochemistry 20 21182262
2021 A novel Lnc408 maintains breast cancer stem cell stemness by recruiting SP3 to suppress CBY1 transcription and increasing nuclear β-catenin levels. Cell death & disease 18 33934099
1982 Molecular heterogeneity of D-end products detected by anti-H-2.28 sera. I. A. molecule similar to Qa-2, detected in the BALB/cBy but not in the BALB/c-H-2dm2 mutant. Immunogenetics 18 6179860
2013 Chibby drives β catenin cytoplasmic accumulation leading to activation of the unfolded protein response in BCR-ABL1+ cells. Cellular signalling 16 23707389
2009 Chibby forms a homodimer through a heptad repeat of leucine residues in its C-terminal coiled-coil motif. BMC molecular biology 16 19435523
2011 The expression patterns and correlations of chibby, β-catenin, and DNA methyltransferase-1 and their clinicopathological significance in lung cancers. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 14 21995627
2013 BCR-ABL1-associated reduction of beta catenin antagonist Chibby1 in chronic myeloid leukemia. PloS one 13 24339928
2005 Chibby, a novel antagonist of the Wnt pathway, is not involved in Wilms tumor development. Cancer letters 13 15737694
2012 Chibby suppresses growth of human SW480 colon adenocarcinoma cells through inhibition of β-catenin signaling. Journal of molecular signaling 12 22651859
2004 Is the gene encoding Chibby implicated as a tumour suppressor in colorectal cancer ? BMC cancer 11 15245581
2020 Role of DZIP1-CBY-FAM92 transition zone complex in the basal body to membrane attachment and ciliary budding. Biochemical Society transactions 9 32491167
2006 Differential Susceptibility of BALB/c and BALB/cBy mice to Graves' hyperthyroidism. Thyroid : official journal of the American Thyroid Association 9 16889488
2021 DZIP1 regulates mammalian cardiac valve development through a Cby1-β-catenin mechanism. Developmental dynamics : an official publication of the American Association of Anatomists 8 33811421
2021 Loss of the ciliary protein Chibby1 in mice leads to exocrine pancreatic degeneration and pancreatitis. Scientific reports 8 34446743
2015 14-3-3 Binding and Sumoylation Concur to the Down-Modulation of β-catenin Antagonist chibby 1 in Chronic Myeloid Leukemia. PloS one 8 26147002
2024 Cep131-Cep162 and Cby-Fam92 complexes cooperatively maintain Cep290 at the basal body and contribute to ciliogenesis initiation. PLoS biology 7 38442096
2015 DNA methyltransferase 1 drives transcriptional down-modulation of β catenin antagonist Chibby1 associated with the BCR-ABL1 gene of chronic myeloid leukemia. Journal of cellular biochemistry 7 25389112
2013 Phosphorylation of C-terminal polycystin-2 influences the interaction with PIGEA14: a QCM study based on solid supported membranes. Biochemical and biophysical research communications 7 23838289
2018 Cloning, identification and function analysis of a Chibby homolog from Litopenaeus vannamei. Fish & shellfish immunology 6 29689303
2017 Chibby 1: a new component of β-catenin-signaling in chronic myeloid leukemia. Oncotarget 6 29152155
2011 Generation and characterization of monoclonal antibodies against human Chibby protein. Hybridoma (2005) 6 21529289
2020 Combined Chibby and β-Catenin Predicts Clinical Outcomes in Patients with Hepatocellular Carcinoma. International journal of molecular sciences 5 32192213
2017 Chibby1 knockdown promotes mesenchymal-to-epithelial transition-like changes. Cell cycle (Georgetown, Tex.) 5 28107095
2016 Conformational characterization of the intrinsically disordered protein Chibby: Interplay between structural elements in target recognition. Protein science : a publication of the Protein Society 5 27082063
2015 Expression of CBY and methylation of CBY at promoter region in human laryngeal squamous cell carcinoma. Tumori 4 25838250
2024 Identification of a novel mutation in chibby family member 2 in a non-obstructive azoospermic patient. Reproductive biology 3 38733656
2018 Anti-oncogenic activity of Chibby in the development of human nasopharyngeal carcinoma. Oncology letters 3 29552214
2014 Downregulated Chibby in laryngeal squamous cell carcinoma with increased expression in laryngeal carcinoma Hep-2 cells. Oncology reports 3 25175341
2023 Elimination of 4T1 Mammary Tumor Cells by BALB/cBy UBC-GFP Transgenics following Stable Inheritance of the H-2b MHC Allele. ImmunoHorizons 2 36637515
2018 Chibby is a weak regulator of β-catenin activity in gastric epithelium. Journal of cellular physiology 2 30063079
2013 No important role for genetic variation in the Chibby gene in monogenic and complex obesity. Molecular biology reports 2 23645032
1999 The H-mshi antigen is conserved among standard BALB/cBy, C57BL/6J, and wild-derived CAST/Ei and SPRET/Ei inbred strains of mice. Immunogenetics 2 10369925
2023 Upregulated TC1 and downregulated Chibby were correlated with the aberrant β-catenin expression in laryngeal squamous cell carcinoma. Medicine 1 37986347
2022 Defective bone repletion in aged Balb/cBy mice was caused by impaired osteoblastic differentiation. Journal of bone and mineral metabolism 1 35947191
2017 Downregulation of nuclear and cytoplasmic Chibby is associated with advanced cervical cancer. Oncology letters 1 29181101
2026 Rhotekin contributes to osteoblast differentiation and bone homeostasis by interacting with Chibby 1. Cellular signalling 0 42000008
2025 Dimerization of the BAR domain-containing protein FAM92A modulates lipid binding and interaction with CBY1. The Journal of biological chemistry 0 40484380

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