Affinage

Showing CTNNBIP1 — ICAT is a alias.

CTNNBIP1

Beta-catenin-interacting protein 1 · UniProt Q9NSA3

Length
81 aa
Mass
9.2 kDa
Annotated
2026-06-09
100 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CTNNBIP1 (ICAT) is a small competitive inhibitor of canonical Wnt signaling that binds beta-catenin and represses beta-catenin-TCF/LEF-mediated transactivation (PMID:10898789). Structurally, an N-terminal 3-helix bundle engages armadillo repeats 10-12 while an extended C-terminal tail occupies the groove of repeats 5-9 used by Tcf/Lef and E-cadherin, allowing ICAT to dissociate beta-catenin-Lef1-p300 complexes and selectively block beta-catenin/Tcf binding without disrupting the cadherin complex (PMID:12408825, PMID:12408824); a Y15/K19/V22 hydrophobic hook contacting beta-catenin F660 is essential for binding, while C-terminal contacts contribute partial inhibition (PMID:28273108). Functionally, ICAT can sequester beta-catenin in the cytoplasm to prevent its nuclear translocation, lowering CCND1 and MYC output (PMID:34569368). ICAT is a direct transcriptional target of E2F1, serving as the node through which E2F1 antagonizes Wnt/beta-catenin signaling (PMID:21532622), a relationship deployed during pre-adipocyte differentiation (PMID:32326181) and downregulated by PLD1 via the PI3K/Akt-TopBP1-E2F1 axis to promote Wnt activity in colorectal cancer (PMID:28939743). Beyond Wnt, ICAT exerts beta-catenin-independent and context-dependent roles: it directly binds the pancreatic transcription factor Ptf1a to repress PTF1 activity by displacing the P/CAF coactivator and impairing Ptf1a acetylation (PMID:23339455), forms a ternary complex with beta-catenin and androgen receptor to augment AR-driven transcription (PMID:21885566), and binds junction plakoglobin (JUP) to activate NF-kappaB-driven migration and invasion (PMID:36036768). In vivo, ICAT loss causes forebrain and craniofacial malformation, renal agenesis from arrested ureteric bud branching with elevated active beta-catenin and Pitx-2, and impaired thymocyte/T-cell survival through reduction of Bcl-xL below a critical threshold (PMID:15148409, PMID:17803964, PMID:20514292, PMID:18511409).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 2000 High

    Established the founding function of ICAT by answering whether a dedicated inhibitor of the beta-catenin-TCF interaction exists.

    Evidence Co-immunoprecipitation, transactivation reporter assays, and Xenopus axis formation

    PMID:10898789

    Open questions at the time
    • Structural basis of selective inhibition unresolved
    • Endogenous regulation of ICAT not addressed
  2. 2002 High

    Resolved how ICAT mechanically discriminates among beta-catenin partners by mapping its two-domain binding mode on the armadillo repeats.

    Evidence X-ray crystallography of ICAT-beta-catenin with complex-dissociation and selectivity assays

    PMID:12408824 PMID:12408825

    Open questions at the time
    • Did not establish physiological contexts of selective Tcf vs p300 vs cadherin displacement
    • In vivo relevance of dissociation activity not tested
  3. 2002 Medium

    Tested whether ICAT could act as a tumor suppressor by killing Wnt-pathway-mutant cancer cells.

    Evidence Adenoviral ICAT overexpression with cell-cycle analysis and xenografts in APC/beta-catenin/AXIN-mutant lines

    PMID:12036951

    Open questions at the time
    • Single lab gain-of-function
    • Mechanism linking Wnt inhibition to G2 arrest and Cdc2 not fully defined
  4. 2003 Medium

    Addressed where ICAT acts and whether it is itself Wnt-regulated, defining its expression pattern and limits of its activity.

    Evidence Subcellular fractionation, immunohistochemistry in intestine, and MDCK scatter assays

    PMID:14613891

    Open questions at the time
    • Mechanism of HGF-enhanced scattering not defined
    • Upstream control of ICAT expression unknown
  5. 2004 High

    Defined the developmental requirement for ICAT by showing its loss disrupts neural anteriorization and organogenesis.

    Evidence ICAT knockout mice and ES-cell neuronal differentiation with Wnt3a epistasis

    PMID:15148409

    Open questions at the time
    • Tissue-specific contributions not separated
    • Downstream Wnt targets in forebrain not identified
  6. 2006 Medium

    Tested the requirement for canonical Wnt/catenin signaling in T-cell development using ICAT as a pathway block.

    Evidence Retroviral ICAT overexpression in thymocyte precursors with flow cytometry

    PMID:16897815

    Open questions at the time
    • Overexpression-based block may exceed physiological inhibition
    • Target genes driving the CD4-8- transition not identified
  7. 2007 Medium

    Linked ICAT loss to a specific organogenesis defect, renal agenesis from ureteric bud arrest.

    Evidence ICAT knockout mouse histology and apoptosis assays in fetal kidney

    PMID:17803964

    Open questions at the time
    • Molecular mediators of UB branching arrest not defined here
    • Single lab
  8. 2008 High

    Placed ICAT's pro-survival role mechanistically by showing beta-catenin/TCF disruption sensitizes T cells to apoptosis through Bcl-xL.

    Evidence ICAT transgenic mice with apoptosis assays, Bcl-xL analysis, and Bcl-2 transgenic rescue

    PMID:18511409

    Open questions at the time
    • Whether endogenous ICAT regulates Bcl-xL not tested
    • Direct transcriptional link between TCF and Bcl-xL not shown
  9. 2010 Medium

    Identified the downstream effector of ICAT loss in kidney as elevated active beta-catenin driving Pitx-2.

    Evidence Knockout mouse microarray, immunohistochemistry, and immunoblotting

    PMID:20514292

    Open questions at the time
    • Causality of Pitx-2 in branching not directly tested
    • c-Ret-independence leaves alternative pathways open
  10. 2011 Medium

    Established ICAT as the node connecting E2F1 and Wnt by showing E2F1 directly transactivates ICAT.

    Evidence Luciferase reporters, ChIP, and E2F1/ICAT gain- and loss-of-function epistasis

    PMID:21532622

    Open questions at the time
    • Physiological contexts of E2F1-ICAT axis not mapped here
    • Single lab
  11. 2011 Medium

    Revealed a non-inhibitory, coactivator-like role for ICAT by showing it forms a ternary complex with beta-catenin and AR and augments AR transcription.

    Evidence GST pulldown, Co-IP, ChIP on PSA promoter, and shRNA in prostate cancer cells

    PMID:21885566

    Open questions at the time
    • Structural basis for AR-beta-catenin retention vs Tcf displacement unclear
    • Single lab
  12. 2013 Medium

    Demonstrated a beta-catenin-independent function by showing ICAT directly represses the pancreatic factor Ptf1a.

    Evidence Yeast two-hybrid, in vitro/in vivo binding, reporter and acetylation assays in acinar tumor cells

    PMID:23339455

    Open questions at the time
    • In vivo pancreatic relevance not established
    • Single lab
  13. 2014 Medium

    Showed ICAT can paradoxically promote metastatic behavior via a beta-catenin-dependent mesenchymal-to-amoeboid switch.

    Evidence Ectopic expression, Matrigel invasion, Rac1/NEDD9 assays, and lung colonization in mice (melanoma)

    PMID:24514042

    Open questions at the time
    • How beta-catenin binding lowers NEDD9/Rac1 mechanistically unclear
    • Context-dependence vs tumor-suppressive role unexplained
  14. 2017 Medium

    Identified competitive displacement of E-cadherin from beta-catenin as a route to ICAT-driven EMT in cervical cancer.

    Evidence Co-IP, overexpression/knockdown, invasion assays, and xenografts in SiHa cells

    PMID:29048651

    Open questions at the time
    • Reconciliation with earlier finding that ICAT spares the cadherin complex needed
    • Single lab
  15. 2017 Medium

    Defined the upstream regulation that suppresses ICAT to license Wnt activity in colorectal cancer.

    Evidence Apc and AOM/DSS mouse models with pathway inhibitor experiments establishing PLD1/PI3K/Akt-TopBP1-E2F1 control of ICAT

    PMID:28939743

    Open questions at the time
    • Direct biochemical link between TopBP1-E2F1 and ICAT promoter not shown
    • Single lab
  16. 2017 Medium

    Pinpointed the binding residues governing ICAT-beta-catenin affinity and target repression.

    Evidence Structure-based mutagenesis with Co-IP and reporter assays on M-MITF/NEDD9 promoters

    PMID:28273108

    Open questions at the time
    • Effects validated only in melanoma promoter context
    • C-terminal contribution only partially defined
  17. 2020 Medium

    Extended the E2F1-ICAT axis to adipogenesis, showing ICAT is required downstream of E2F1 to permit differentiation.

    Evidence ICAT overexpression and siRNA epistasis in 3T3-L1 differentiation assays

    PMID:32326181

    Open questions at the time
    • In vivo adipogenic role not tested
    • Single lab
  18. 2021 Medium

    Clarified the subcellular mechanism of Wnt inhibition by showing cytoplasmic ICAT sequesters beta-catenin to block nuclear entry.

    Evidence Co-IP, immunofluorescence co-localization, TOPflash, and xenografts in CRC lines

    PMID:34569368

    Open questions at the time
    • Quantitative contribution of sequestration vs displacement unclear
    • Single lab
  19. 2022 Medium

    Identified JUP as a beta-catenin-homolog partner mediating an ICAT-driven, NF-kappaB-dependent pro-metastatic program.

    Evidence Co-IP/mass spectrometry, JUP knockdown epistasis, and lung metastasis model in CRC

    PMID:36036768

    Open questions at the time
    • Direct ICAT-JUP binding interface not mapped
    • Mechanism of NF-kappaB activation unresolved
  20. 2025 Medium

    Connected ICAT to metabolic reprogramming and immune evasion via c-Myc-driven glycolysis and lactylation-mediated macrophage polarization.

    Evidence c-Myc translocation, ENO1 transcription, macrophage co-culture, H3K18 lactylation, and in vivo tumor models (cervical cancer)

    PMID:40976412

    Open questions at the time
    • How ICAT facilitates c-Myc nuclear translocation not defined
    • Single lab
  21. 2025 Low

    Proposed a cardioprotective role for ICAT as a negative regulator of hypertrophy via the beta-catenin/ERK axis.

    Evidence ICAT overexpression in cardiomyocytes with proteomics, surface-area, and ERK phosphorylation assays plus HFD/L-NAME mice

    PMID:40903537

    Open questions at the time
    • Single overexpression experiment without loss-of-function rescue
    • Direct link between beta-catenin and ERK not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how ICAT switches between beta-catenin-dependent inhibition, coactivator-like AR support, and beta-catenin-independent transcriptional repression in a context-specific manner.
  • No unified model reconciling tumor-suppressive vs pro-metastatic roles
  • Endogenous regulators determining context not identified
  • No structural data for ICAT-JUP or ICAT-Ptf1a complexes

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0060090 molecular adaptor activity 2 GO:0140110 transcription regulator activity 2 GO:0140313 molecular sequestering activity 1
Localization
GO:0005829 cytosol 2 GO:0005634 nucleus 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-1266738 Developmental Biology 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
ARCDH1CTNNB1EP300JUPLEF1PTF1ATCF7L2

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 ICAT (CTNNBIP1) was identified as a novel beta-catenin-interacting protein that inhibits the interaction of beta-catenin with TCF-4, thereby repressing beta-catenin-TCF-4-mediated transactivation and inhibiting Xenopus axis formation by interfering with Wnt signaling. Co-immunoprecipitation, transactivation reporter assays, Xenopus axis formation assay Genes & development High 10898789
2002 Crystal structure of ICAT bound to the armadillo repeat domain of beta-catenin revealed that ICAT contains an N-terminal helical domain binding to repeats 11-12 of beta-catenin and an extended C-terminal region binding repeats 5-10 similarly to Tcf/Lef. Full-length ICAT dissociates complexes of beta-catenin, Lef-1, and the coactivator p300, while the helical domain alone selectively blocks binding to p300. X-ray crystallography, in vitro complex dissociation assays, domain truncation experiments Molecular cell High 12408825
2002 Crystal structure of the beta-catenin/ICAT complex at 2.5 Å resolution showed that ICAT contains a 3-helix bundle binding armadillo repeats 10-12 and a C-terminal tail binding the groove of armadillo repeats 5-9 similarly to Tcf and E-cadherin. ICAT selectively inhibits beta-catenin/Tcf binding in vivo without disrupting the beta-catenin/cadherin interaction. X-ray crystallography, in vivo co-immunoprecipitation, selectivity assays Molecular cell High 12408824
2002 Overexpression of ICAT inhibits proliferation of colorectal tumor cells with APC or beta-catenin mutations and hepatocellular carcinoma cells with AXIN mutations, inhibits G2 progression by blocking Cdc2 dephosphorylation and nuclear translocation of cyclin B1, leading to G2 arrest and cell death. ICAT did not inhibit growth of normal or tumor cells with wild-type APC/beta-catenin/Axin. Recombinant adenovirus-mediated ICAT overexpression, cell cycle analysis, xenograft tumor model Cancer research Medium 12036951
2003 ICAT localizes to both cytoplasmic and nuclear compartments. ICAT is upregulated in mature non-dividing enterocytes lining intestinal villi and absent in the beta-catenin/TCF signaling-active crypt region. ICAT protein levels are not altered by activation or inhibition of Wnt signaling in cultured cells, indicating ICAT expression is not a direct Wnt/beta-catenin target. ICAT does not protect soluble beta-catenin from APC-containing destruction complex degradation. Stable ICAT overexpression in MDCK cells did not disrupt the cadherin complex but enhanced cell scattering on HGF treatment. Subcellular fractionation, immunofluorescence, immunohistochemistry in intestinal tissue, stable overexpression in MDCK cells, scatter assay American journal of physiology. Cell physiology Medium 14613891
2004 ICAT knockout (ICAT-/-) embryos exhibit malformation of the forebrain and craniofacial bones and lack the kidney. ICAT promotes anteriorization of neural fate by inhibiting the posteriorizing activity of Wnt3a signaling; ICAT-/- embryonic stem cells differentiate into neuronal cells with posterior character. Knockout mouse model, embryonic stem cell differentiation assays, neuronal fate analysis Proceedings of the National Academy of Sciences of the United States of America High 15148409
2006 ICAT overexpression by retroviral gene targeting in CD4-8- thymocytes inhibits the CD4-8- to CD4+8+ transition but not later transitions, demonstrating that canonical Wnt/catenin signaling (via beta- and gamma-catenin binding to Tcf/Lef) is required for early T cell precursor maturation. Retroviral ICAT overexpression in thymocyte precursors, flow cytometric analysis of T cell development stages European journal of immunology Medium 16897815
2007 Loss of ICAT gene function in mice causes arrest of ureteric bud (UB) branching and renal agenesis; ICAT-/- metanephros show delayed UB branching, increased apoptosis of metanephric mesenchymal cells, and renal agenesis. ICAT knockout mouse model, histology, apoptosis assays in fetal kidney Biochemical and biophysical research communications Medium 17803964
2008 Disruption of beta-catenin/TCF interaction by ICAT transgenic expression in adult mice renders thymocytes and activated T cells highly susceptible to apoptosis by reducing Bcl-xL expression below a critical threshold; transgenic Bcl-2 expression rescued activated ICAT-Tg CD4 T cells from apoptosis. Transgenic mouse expressing ICAT, apoptosis assays, Bcl-xL expression analysis, Bcl-2 transgenic rescue International immunology High 18511409
2010 In ICAT-/- kidneys, active beta-catenin protein level is elevated and the Wnt target gene Pitx-2 is enhanced, while c-Ret expression is unchanged, suggesting that Pitx-2 upregulation downstream of activated Wnt signaling mediates delays in ureteric bud branching. Knockout mouse model, DNA microarray, immunohistochemistry, immunoblotting Acta histochemica et cytochemica Medium 20514292
2011 ICAT is a direct transcriptional target of E2F1; E2F1 activates ICAT expression, and this activation is required for E2F1 to inhibit beta-catenin transcriptional activity, establishing ICAT as the node mediating cross-talk between E2F1 and Wnt/beta-catenin signaling pathways. Luciferase reporter assays, ChIP, E2F1 gain- and loss-of-function, ICAT knockdown epistasis Oncogene Medium 21532622
2011 ICAT forms a ternary complex with beta-catenin and androgen receptor (AR) in prostate cancer cells. The N-terminal helical domain of ICAT retains rather than displaces the AR-beta-catenin interaction. ICAT expression augments ligand-dependent AR-mediated transcription and enhances expression of PSA and KLK2 androgen-response genes. ICAT is recruited to the PSA promoter in LNCaP cells. GST pulldown, co-immunoprecipitation, chromatin immunoprecipitation (ChIP), shRNA knockdown, stable ICAT overexpression in prostate cancer cell lines Molecular endocrinology (Baltimore, Md.) Medium 21885566
2013 ICAT interacts with the pancreatic transcription factor Ptf1a (identified by yeast two-hybrid screening and validated in vitro and in vivo). ICAT negatively regulates PTF1 transcriptional activity independently of beta-catenin by directly binding Ptf1a, displacing the coactivator P/CAF, reducing the Ptf1a-Rbpjl interaction, and impairing Ptf1a acetylation by P/CAF. Yeast two-hybrid, in vitro binding assays, co-immunoprecipitation in acinar tumor cells, reporter assays, acetylation assays The Biochemical journal Medium 23339455
2014 Ectopic ICAT expression in metastatic melanoma cells did not affect proliferation but increased cell motility and Matrigel invasion, converting cells from elongated/mesenchymal to round/amoeboid morphology. This transition was dependent on stable ICAT-beta-catenin interaction and associated with decreased levels of NEDD9 and activated Rac1, and promoted lung colonization in nude mice. Ectopic ICAT expression, Matrigel invasion assays, morphological analysis, Rac1 activity assays, in vivo lung colonization model Cancer research Medium 24514042
2017 ICAT promotes cervical cancer EMT by competing with E-cadherin for binding to beta-catenin (disrupting the E-cadherin/beta-catenin complex), as demonstrated by co-immunoprecipitation assays. ICAT overexpression promoted SiHa cell proliferation and enhanced migration/invasion, while knockdown had opposite effects. Co-immunoprecipitation, ICAT overexpression and knockdown, in vitro proliferation/migration/invasion assays, xenograft mouse model Oncology reports Medium 29048651
2017 PLD1 promotes Wnt/beta-catenin signaling by selectively downregulating ICAT via the PI3K/Akt-TopBP1-E2F1 signaling pathway, establishing ICAT as a node of cross-talk between PLD1/PI3K/Akt and Wnt/beta-catenin pathways in colorectal cancer. In vivo mouse models (Apc+, AOM/DSS), colorectal cancer cell lines, pathway inhibitor experiments, gene expression analysis Clinical cancer research Medium 28939743
2017 Structure-based mutagenesis of ICAT showed that Y15, K19, and V22 in the N-terminal helical domain contact beta-catenin F660; abolishing this hydrophobic hook interaction completely eliminated ICAT-beta-catenin binding. In the C-terminal tail, neutralizing electrostatic interactions (D66, E75) plus deletion of F71 hydrophobic contact markedly reduced but did not abolish ICAT-mediated inhibition of M-MITF and NEDD9 promoters. Site-directed mutagenesis, co-immunoprecipitation, luciferase reporter assays for target gene promoters in melanoma cells PloS one Medium 28273108
2020 E2F1 promotes pre-adipocyte differentiation by activating ICAT, which in turn represses Wnt/beta-catenin activity. ICAT overexpression in 3T3-L1 pre-adipocytes promotes adipogenesis and partially reverses beta-catenin activation-induced inhibition of differentiation. Gene silencing of ICAT in E2F1-overexpressing cells inhibited adipogenesis, confirming ICAT is required downstream of E2F1. ICAT overexpression, siRNA knockdown epistasis, 3T3-L1 differentiation assays, lipid accumulation assays, Western blotting Cells Medium 32326181
2021 ICAT overexpression in CRC stable cell lines binds beta-catenin in the cytoplasm (confirmed by co-immunoprecipitation and co-localization by immunofluorescence), preventing its nuclear translocation and inactivating Wnt signaling with reduction of CCND1 and MYC downstream targets. Co-immunoprecipitation, immunofluorescence, ICAT stable overexpression, TOPflash reporter, in vivo xenograft Technology in cancer research & treatment Medium 34569368
2022 ICAT overexpression promotes colorectal cancer cell migration and invasion in vitro and tumor metastasis in vivo by interacting with junction plakoglobin (JUP), a beta-catenin homolog; JUP downregulation impairs ICAT-induced migration. Additionally, ICAT overexpression activates the NF-κB signaling pathway to enhance migration/invasion. Co-IP/mass spectrometry, STRING database validation, immunofluorescence, wound healing and transwell assays, in vivo lung metastasis model Journal of clinical laboratory analysis Medium 36036768
2025 ICAT facilitates nuclear translocation of c-Myc in cervical cancer cells, enhancing ENO1 transcription and promoting glycolytic activity and lactate accumulation. Tumor-derived lactate induces H3K18 lactylation in tumor-associated macrophages, activating ARG1 expression and driving M2 polarization to create an immunosuppressive tumor microenvironment. Mechanistic cell-based assays, c-Myc nuclear translocation analysis, ENO1 transcription assays, macrophage co-culture, H3K18 lactylation detection, in vivo tumor models Free radical biology & medicine Medium 40976412
2025 In a cardiac hypertrophy model, overexpression of ICAT suppressed isoproterenol-induced increases in beta-catenin, phosphorylated ERK, and cardiomyocyte surface area, establishing ICAT as a negative regulator of cardiac hypertrophy via the beta-catenin/ERK axis. ICAT overexpression in cardiomyocytes, LC-MS proteomics, cardiomyocyte surface area measurement, ERK phosphorylation assays, in vivo HFD/L-NAME mouse model Hypertension research Low 40903537

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Inhibition of Wnt signaling by ICAT, a novel beta-catenin-interacting protein. Genes & development 276 10898789
2018 CircRNA circRNA_102171 promotes papillary thyroid cancer progression through modulating CTNNBIP1-dependent activation of β-catenin pathway. Journal of experimental & clinical cancer research : CR 198 30424816
2016 Multicenter Feasibility Study of Tumor Molecular Profiling to Inform Therapeutic Decisions in Advanced Pediatric Solid Tumors: The Individualized Cancer Therapy (iCat) Study. JAMA oncology 174 26822149
2002 ICAT inhibits beta-catenin binding to Tcf/Lef-family transcription factors and the general coactivator p300 using independent structural modules. Molecular cell 144 12408825
2004 Isotope-coded affinity tag (ICAT) approach to redox proteomics: identification and quantitation of oxidant-sensitive cysteine thiols in complex protein mixtures. Journal of proteome research 134 15595732
2002 The crystal structure of the beta-catenin/ICAT complex reveals the inhibitory mechanism of ICAT. Molecular cell 101 12408824
2017 Assessing the complexity of interventions within systematic reviews: development, content and use of a new tool (iCAT_SR). BMC medical research methodology 98 28446138
2014 MiR-424-5p reversed epithelial-mesenchymal transition of anchorage-independent HCC cells by directly targeting ICAT and suppressed HCC progression. Scientific reports 96 25175916
2002 Molecular genetic analysis of malignant melanomas for aberrations of the WNT signaling pathway genes CTNNB1, APC, ICAT and BTRC. International journal of cancer 94 12124804
2018 Linc00210 drives Wnt/β-catenin signaling activation and liver tumor progression through CTNNBIP1-dependent manner. Molecular cancer 93 29540185
2008 Quantitative analysis of redox-sensitive proteome with DIGE and ICAT. Journal of proteome research 89 18707151
2003 The application of new software tools to quantitative protein profiling via isotope-coded affinity tag (ICAT) and tandem mass spectrometry: II. Evaluation of tandem mass spectrometry methodologies for large-scale protein analysis, and the application of statistical tools for data analysis and interpretation. Molecular & cellular proteomics : MCP 83 12832459
2014 Monitoring in vivo reversible cysteine oxidation in proteins using ICAT and mass spectrometry. Nature protocols 76 24743420
2007 Mascot file parsing and quantification (MFPaQ), a new software to parse, validate, and quantify proteomics data generated by ICAT and SILAC mass spectrometric analyses: application to the proteomics study of membrane proteins from primary human endothelial cells. Molecular & cellular proteomics : MCP 75 17533220
2013 Functional implications of microRNA-215 in TGF-β1-induced phenotypic transition of mesangial cells by targeting CTNNBIP1. PloS one 73 23554908
2003 Role for ICAT in beta-catenin-dependent nuclear signaling and cadherin functions. American journal of physiology. Cell physiology 67 14613891
2021 Bruceine D inhibits HIF-1α-mediated glucose metabolism in hepatocellular carcinoma by blocking ICAT/β-catenin interaction. Acta pharmaceutica Sinica. B 65 34900531
2015 miR-603 promotes glioma cell growth via Wnt/β-catenin pathway by inhibiting WIF1 and CTNNBIP1. Cancer letters 65 25681036
2011 Distinction of thioredoxin transnitrosylation and denitrosylation target proteins by the ICAT quantitative approach. Journal of proteomics 62 21704743
2013 ICAT: Development of an Internet-Based Data Collection Method for Ecological Momentary Assessment Using Personal Cell Phones. European journal of psychological assessment : official organ of the European Association of Psychological Assessment 61 24285917
2004 A comparative proteomic strategy for subcellular proteome research: ICAT approach coupled with bioinformatics prediction to ascertain rat liver mitochondrial proteins and indication of mitochondrial localization for catalase. Molecular & cellular proteomics : MCP 61 15507458
2007 Biomarkers and diagnosis; protein biomarkers in serum of pediatric patients with severe traumatic brain injury identified by ICAT-LC-MS/MS. Journal of neurotrauma 56 17263670
2004 A dataset of human liver proteins identified by protein profiling via isotope-coded affinity tag (ICAT) and tandem mass spectrometry. Molecular & cellular proteomics : MCP 51 15269248
2004 Anteriorization of neural fate by inhibitor of beta-catenin and T cell factor (ICAT), a negative regulator of Wnt signaling. Proceedings of the National Academy of Sciences of the United States of America 50 15148409
2013 Redox proteomics of thiol proteins in mouse heart during ischemia/reperfusion using ICAT reagents and mass spectrometry. Free radical biology & medicine 49 23376233
2005 ICAT-based comparative proteomic analysis of non-replicating persistent Mycobacterium tuberculosis. Tuberculosis (Edinburgh, Scotland) 49 16376151
2003 The application of new software tools to quantitative protein profiling via isotope-coded affinity tag (ICAT) and tandem mass spectrometry: I. Statistically annotated datasets for peptide sequences and proteins identified via the application of ICAT and tandem mass spectrometry to proteins copurifying with T cell lipid rafts. Molecular & cellular proteomics : MCP 48 12832456
2011 The oxidized thiol proteome in fission yeast--optimization of an ICAT-based method to identify H2O2-oxidized proteins. Journal of proteomics 45 21672643
2017 Phospholipase D1 Inhibition Linked to Upregulation of ICAT Blocks Colorectal Cancer Growth Hyperactivated by Wnt/β-Catenin and PI3K/Akt Signaling. Clinical cancer research : an official journal of the American Association for Cancer Research 42 28939743
2002 Overexpression of Icat induces G(2) arrest and cell death in tumor cell mutants for adenomatous polyposis coli, beta-catenin, or Axin. Cancer research 42 12036951
2006 Overexpression of ICAT highlights a role for catenin-mediated canonical Wnt signalling in early T cell development. European journal of immunology 40 16897815
2016 The oxidized thiol proteome in aging and cataractous mouse and human lens revealed by ICAT labeling. Aging cell 39 28177569
2010 Serum protein biomarkers screening in HCC patients with liver cirrhosis by ICAT-LC-MS/MS. Journal of cancer research and clinical oncology 38 20130913
2007 Protein markers of ischemic insult in brain endothelial cells identified using 2D gel electrophoresis and ICAT-based quantitative proteomics. Journal of proteome research 38 17203967
2005 Cold adaptation of the Antarctic archaeon, Methanococcoides burtonii assessed by proteomics using ICAT. Journal of proteome research 38 15822924
2015 Targeting the Wnt-Regulatory Protein CTNNBIP1 by microRNA-214 Enhances the Stemness and Self-Renewal of Cancer Stem-Like Cells in Lung Adenocarcinomas. Stem cells (Dayton, Ohio) 37 26299367
2001 Molecular cloning and characterization of LZIC, a novel gene encoding ICAT homologous protein with leucine zipper domain. International journal of molecular medicine 37 11712074
2014 ICAT inhibits glioblastoma cell proliferation by suppressing Wnt/β-catenin activity. Cancer letters 36 25434796
2005 Application of isotope coded affinity tag (ICAT) analysis for the identification of differentially expressed proteins following infection of atlantic salmon (Salmo salar) with infectious hematopoietic necrosis virus (IHNV) or Renibacterium salmoninarum (BKD). Journal of proteome research 36 15822907
2006 Synthesis of acid-cleavable light isotope-coded affinity tags (ICAT-L) for potential use in proteomic expression profiling analysis. Bioconjugate chemistry 32 16417277
2018 CTNNBIP1 downregulation is associated with tumor grade and viral infections in gastric adenocarcinoma. Journal of cellular physiology 30 30076728
2011 E2F1 suppresses Wnt/β-catenin activity through transactivation of β-catenin interacting protein ICAT. Oncogene 29 21532622
2005 An optimized strategy for ICAT quantification of membrane proteins. Molecular & cellular proteomics : MCP 29 16216825
2021 MiR-486-3p promotes osteogenic differentiation of BMSC by targeting CTNNBIP1 and activating the Wnt/β-catenin pathway. Biochemical and biophysical research communications 28 34118593
2014 β-catenin inhibitor ICAT modulates the invasive motility of melanoma cells. Cancer research 28 24514042
2017 Inhibitor of β-catenin and TCF (ICAT) promotes cervical cancer growth and metastasis by disrupting E-cadherin/β-catenin complex. Oncology reports 27 29048651
2014 MiR-29b controls fetal mouse neurogenesis by regulating ICAT-mediated Wnt/β-catenin signaling. Cell death & disease 26 25321480
2010 Identification of cellular MMP substrates using quantitative proteomics: isotope-coded affinity tags (ICAT) and isobaric tags for relative and absolute quantification (iTRAQ). Methods in molecular biology (Clifton, N.J.) 26 20135298
2016 MicroRNA-215 impairs adipocyte differentiation and co-represses FNDC3B and CTNNBIP1. The international journal of biochemistry & cell biology 25 27521659
2008 ICAT expression disrupts beta-catenin-TCF interactions and impairs survival of thymocytes and activated mature T cells. International immunology 25 18511409
2002 Mutation and expression of the beta-catenin-interacting protein ICAT in human colorectal tumors. Japanese journal of clinical oncology 24 12417602
2010 Quantitative proteomic analysis of S-nitrosated proteins in diabetic mouse liver with ICAT switch method. Protein & cell 20 21203939
2020 E2F1 Regulates Adipocyte Differentiation and Adipogenesis by Activating ICAT. Cells 19 32326181
2014 Effects of genistein and daidzein on cell proliferation kinetics in HT29 colon cancer cells: the expression of CTNNBIP1 (β-catenin), APC (adenomatous polyposis coli) and BIRC5 (survivin). Human cell 19 24390805
2019 Piplartine suppresses proliferation and invasion of hepatocellular carcinoma by LINC01391-modulated Wnt/β-catenin pathway inactivation through ICAT. Cancer letters 18 31207322
2008 A mechanism-based ICAT strategy for comparing relative expression and activity levels of glycosidases in biological systems. Journal of proteome research 18 18563928
2006 Protein profiling of sickle cell versus control RBC core membrane skeletons by ICAT technology and tandem mass spectrometry. Cellular & molecular biology letters 17 16847560
2011 Orai1 and Ca2+-independent phospholipase A2 are required for store-operated Icat-SOC current, Ca2+ entry, and proliferation of primary vascular smooth muscle cells. American journal of physiology. Cell physiology 16 22094335
2006 Proteomic analysis of opsins and thyroid hormone-induced retinal development using isotope-coded affinity tags (ICAT) and mass spectrometry. Molecular vision 16 16785855
2020 miR‑296‑3p promotes the proliferation of glioblastoma cells by targeting ICAT. Molecular medicine reports 15 32323769
2004 Infrequent somatic mutations of the ICAT gene in various human cancers with frequent 1p-LOH and/or abnormal nuclear accumulation of beta-catenin. Oncology reports 15 15492799
2024 Disruption of PABPN1 phase separation by SNRPD2 drives colorectal cancer cell proliferation and migration through promoting alternative polyadenylation of CTNNBIP1. Science China. Life sciences 14 38811444
2019 The Alteration of CTNNBIP1 in Lung Cancer. International journal of molecular sciences 14 31766223
2005 ICAT-MS-MS time course analysis of atrophying mouse skeletal muscle cytosolic subproteome. Molecular bioSystems 14 16880987
2011 The beta-catenin binding protein ICAT modulates androgen receptor activity. Molecular endocrinology (Baltimore, Md.) 13 21885566
2008 ICAT participates in proliferation and osteogenic differentiation of human adipose tissue-derived mesenchymal stem cell. Life sciences 11 18977368
2023 The HPV16 E6, E7/miR-23b-3p/ICAT signaling axis promotes proliferation, migration, invasion and EMT of cervical cancer cells. Carcinogenesis 10 36847693
2021 The CTNNBIP1-CLSTN1 fusion transcript regulates human neocortical development. Cell reports 10 34192541
2021 Overexpression of ICAT Inhibits the Progression of Colorectal Cancer by Binding with β-Catenin in the Cytoplasm. Technology in cancer research & treatment 10 34569368
2022 ICAT promotes colorectal cancer metastasis via binding to JUP and activating the NF-κB signaling pathway. Journal of clinical laboratory analysis 8 36036768
2020 CTNNBIP1 modulates keratinocyte proliferation through promoting the transcription of β-catenin/TCF complex downstream genes. Journal of the European Academy of Dermatology and Venereology : JEADV 8 32531088
2020 Functional genetic variants of CTNNBIP1 predict platinum treatment response of Chinese epithelial ovarian cancer patients. Journal of Cancer 8 33123276
2016 MicroRNA-1301 induces cell proliferation by downregulating ICAT expression in breast cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 8 33027881
2008 Synthesis and proteomic activity evaluation of a new isotope-coded affinity tagging (ICAT) reagent. Bioconjugate chemistry 8 18407682
2021 The Circ_CARM1 controls cell migration by regulating CTNNBIP1 in anti-benzo[a]pyrene-trans-7,8-dihydrodiol-9,10-epoxide-transformed 16HBE cells. Toxicology letters 7 34052308
2023 ICAT: a novel algorithm to robustly identify cell states following perturbations in single-cell transcriptomes. Bioinformatics (Oxford, England) 6 37086439
2023 miR-342-5p targets CTNNBIP1 to promote enterovirus 71 replication. Microbial pathogenesis 6 37479047
2013 ICAT is a novel Ptf1a interactor that regulates pancreatic acinar differentiation and displays altered expression in tumours. The Biochemical journal 6 23339455
2007 Loss of ICAT gene function leads to arrest of ureteric bud branching and renal agenesis. Biochemical and biophysical research communications 6 17803964
2025 ICAT drives lactylation of tumor-associated macrophages via the c-Myc-ENO1 axis to promote cervical cancer progression. Free radical biology & medicine 5 40976412
2022 A multicenter, open-label, randomized, proof-of-concept phase II clinical trial to assess the efficacy and safety of icatibant in patients infected with SARS-CoV-2 (COVID-19) and admitted to hospital units without invasive mechanical ventilation: study protocol (ICAT-COVID). Trials 5 35413921
2022 icaR and icaT are Ancient Chromosome Genes Encoding Substrates of the Type III Secretion Apparatus in Shigella flexneri. mSphere 5 35582904
2020 Implementation of C-reactive protein point of care testing to improve antibiotic targeting in respiratory illness in Vietnamese primary care (ICAT): a study protocol for a cluster randomised controlled trial. BMJ open 5 33361164
2007 The EIPeptiDi tool: enhancing peptide discovery in ICAT-based LC MS/MS experiments. BMC bioinformatics 5 17631686
2023 CTNNBIP1-CLSTN1 functions as a housekeeping chimeric RNA and regulates cell proliferation through SERPINE2. Cell death discovery 4 37805599
2022 Knockout of ICAT in Adipose Tissue Alleviates Fibro-inflammation in Obese Mice. Inflammation 4 36181623
2017 Structure-based mutational analysis of ICAT residues mediating negative regulation of β-catenin co-transcriptional activity. PloS one 4 28273108
2009 ICAT as a potential enhancer of monocytic differentiation: implications from the comparative proteome analysis of the HL60 cell line stimulated by all-trans retinoic acid and NSC67657. Cell biochemistry and function 4 19569129
2019 Leucine zipper and ICAT domain containing (LZIC) protein regulates cell cycle transitions in response to ionizing radiation. Cell cycle (Georgetown, Tex.) 3 30973299
2017 Opposing roles of ICAT and Wnt/β-catenin signaling in NSC67657-induced monocytic differentiation. Oncotarget 3 29050252
2021 iCAT: diagnostic assessment tool of immunological history using high-throughput T-cell receptor sequencing. F1000Research 2 34316355
2019 Treatment rationale and design of the induction chemotherapy and adjuvant thoracic radiation in resectable N2-3A/3B non-small cell lung cancer (ICAT) study. Medicine 2 31277165
2010 High expression of Pitx-2 in the ICAT-deficient metanephros leads to developmental arrest. Acta histochemica et cytochemica 2 20514292
2025 Pathophysiology of COVID-19: A Post Hoc Analysis of the ICAT-COVID Clinical Trial of the Bradykinin Antagonist Icatibant. Pathogens (Basel, Switzerland) 1 40559541
2025 miR-423-3p inhibits CTNNBIP1/WNT preventing hyperandrogenic polycystic ovary syndrome†. Biology of reproduction 1 40600659
2025 Goreisan attenuates cardiac hypertrophy and diastolic dysfunction in heart failure with preserved ejection fraction induced by HFD/L-NAME via regulation of ICAT-β-catenin/ERK axis. Hypertension research : official journal of the Japanese Society of Hypertension 1 40903537
2025 PKCζ, CTNNBIP1 and ALDH1A3 Expression in Luminal B Breast Cancer Indicates Decreased Hormone Therapy Effectiveness. Cancer diagnosis & prognosis 1 41179319
2024 ICAT-Mediated Crosstalk Between Cervical Cancer Cells and Macrophages Promotes M2-Like Macrophage Polarization to Reinforce Tumor Malignant Behaviors. Molecular carcinogenesis 1 39279723
2016 [Expression of ICAT and Wnt signaling-related proteins in the monocytic differentiation of HL-60 cells induced by a new steroidal drug NSC67657]. Zhonghua zhong liu za zhi [Chinese journal of oncology] 1 27087369
2023 CTNNBIP1-CLSTN1 Functions as a Housekeeping Chimeric RNA, and Regulates Cell Proliferation through SERPINE2. Research square 0 37503100

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