Affinage

AXIN1

Axin-1 · UniProt O15169

Length
862 aa
Mass
95.6 kDa
Annotated
2026-06-09
100 papers in source corpus 38 papers cited in narrative 38 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

AXIN1 is a multifunctional scaffold that acts as a negative regulator of Wnt/β-catenin signaling, with restoration of wild-type AXIN1 inducing apoptosis in cancer cells bearing APC, CTNNB1, or AXIN1 mutations and suppressing TCF/β-catenin transcription (PMID:10700176, PMID:11390362). Its central region is intrinsically disordered, enabling the dynamic kinase–substrate contacts that bring GSK3β and β-catenin together for phosphorylation (PMID:21087614), and peptide-level mapping defines discrete binding epitopes within this region for partners including CK1ε, c-Myc, Pin1, and p53 (PMID:30166345). Within an intact AXIN1-organized destruction complex, β-catenin is phosphorylated, ubiquitinated, and degraded; Wnt signaling does not disassemble this complex but suppresses β-catenin ubiquitination, saturating the complex with phospho-β-catenin so that newly synthesized free β-catenin accumulates (PMID:22682247). Systematic analysis of tumor-associated missense variants shows that loss-of-function mutations selectively abolish binding to the partner corresponding to the mutated domain (GSK3β, β-catenin, or RGS/APC), and that truncated AXIN1 loses β-catenin regulatory function (PMID:38359148). Beyond β-catenin, AXIN1 scaffolds a c-Myc degradation complex with GSK3β, Pin1, and PP2A-B56α, controlling the T58/S62 phosphorylation balance that governs c-Myc stability (PMID:19131971, PMID:21808024), and it physically engages NRF2 to restrain an antioxidant gene program (PMID:25336178) and YAP/TAZ to limit their nuclear accumulation (PMID:35921500). In vivo, hepatocyte- or mesenchyme-specific Axin1 loss drives proliferation and tumorigenesis through β-catenin and cooperating YAP/TAZ, FGF/ERK, or BMP signaling (PMID:22960659, PMID:30737831, PMID:35921500, PMID:36541713), establishing AXIN1 as a tumor suppressor whose dosage is tightly controlled by E3 ligases (TRIM65, TRIM11) and deubiquitinases (USP44, UCHL5) acting on its stability and polymerization (PMID:28754688, PMID:32285989, PMID:35256667), by transcriptional inputs from RUNX1 and VDR (PMID:26916619, PMID:27601169), and by m6A-directed mRNA decay via YTHDF2 (PMID:33980824). AXIN1 also operates outside growth control: it stabilizes the antiviral factor IRF3 via USP35-mediated deubiquitination and undergoes TBK1-driven phase separation to boost type I interferon production (PMID:39384753), scaffolds AMPK/LKB1 signaling in contracting muscle (PMID:31846370), and links γ-protocadherin-C3 to dendritic arborization in cortical neurons (PMID:36604170).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2000 High

    Established AXIN1 as a tumor-suppressing negative regulator of Wnt signaling whose restoration kills cancer cells with destruction-complex mutations.

    Evidence Adenoviral AXIN1 transfer and TCF DNA-binding assays in hepatocellular and colorectal cancer lines

    PMID:10700176

    Open questions at the time
    • Did not resolve the molecular architecture of the complex
    • Mechanism of apoptosis induction not defined
  2. 2001 High

    Localized AXIN1's Wnt-suppressing function to its GSK3-binding domain and confirmed the role in vivo through a developmental patterning phenotype.

    Evidence Zebrafish masterblind allele mapping, GSK3/Axin1 binding assay, and rescue by overexpression

    PMID:11390362

    Open questions at the time
    • Did not address mammalian destruction-complex stoichiometry
    • Other domain functions untested
  3. 2009 High

    Extended AXIN1 scaffolding beyond β-catenin to c-Myc, showing it assembles a c-Myc degradation complex controlling T58/S62 phosphorylation.

    Evidence Reciprocal Co-IP, siRNA knockdown, and phosphorylation assays with GSK3β, Pin1, PP2A-B56α

    PMID:19131971

    Open questions at the time
    • Single-lab finding
    • Quantitative contribution to c-Myc turnover in vivo unclear
  4. 2010 High

    Provided the biophysical basis for AXIN1 scaffolding by showing its central region is intrinsically disordered, enabling dynamic kinase-substrate engagement.

    Evidence NMR, circular dichroism, and analytical ultracentrifugation of the central region

    PMID:21087614

    Open questions at the time
    • Structure of the assembled complex not resolved
    • Disorder-to-binding transitions not mapped at residue level
  5. 2012 High

    Redefined the Wnt mechanism by showing the destruction complex stays intact and that Wnt suppresses β-catenin ubiquitination, leading to complex saturation rather than disassembly.

    Evidence Endogenous IP-MS, proteasome inhibition, and Wnt stimulation in colorectal cells and primary intestinal epithelium

    PMID:22682247

    Open questions at the time
    • Molecular trigger of ubiquitination suppression not fully defined
    • Role of AXIN1 vs AXIN2 not distinguished here
  6. 2014 High

    Connected AXIN1 to redox homeostasis by demonstrating a physical complex with NRF2 that restrains the antioxidant program.

    Evidence Reciprocal Co-IP with domain mapping, tankyrase inhibitors, and conditional liver KO mice

    PMID:25336178

    Open questions at the time
    • Whether NRF2 regulation is destruction-complex dependent unclear
    • Direct fate of NRF2 within the complex not defined
  7. 2018 Medium

    Mapped discrete binding epitopes across the AXIN1 disordered region and showed competition with Dishevelled for CK1ε.

    Evidence Peptide microarray, in vitro binding, and competitive peptide/deletion variant assays

    PMID:30166345

    Open questions at the time
    • In vitro mapping not all validated in cells
    • Functional hierarchy among epitopes unresolved
  8. 2024 High

    Systematically defined how tumor mutations inactivate AXIN1 by abolishing domain-specific partner binding, linking genotype to β-catenin activation.

    Evidence Co-IP for each domain partner and β-catenin reporter assays across 80 missense variants

    PMID:38359148

    Open questions at the time
    • Variant effects on non-Wnt functions not tested
    • In vivo pathogenicity of individual variants not established
  9. 2024 High

    Revealed an AXIN1 role in innate antiviral immunity through IRF3 stabilization and TBK1-driven phase separation.

    Evidence Co-IP, K48-linkage-specific ubiquitination, autophagic flux, phase separation imaging, and RGS-ligand pharmacology

    PMID:39384753

    Open questions at the time
    • Physiological relevance to host antiviral defense in vivo limited
    • Interplay with Wnt scaffolding function unclear
  10. 2022 Medium

    Demonstrated AXIN1 stability is governed by deubiquitinases controlling both protein level and polymerization independently of catalytic activity.

    Evidence Domain-binding Co-IP, polymerization assays, and catalytic UCHL5 mutant analysis

    PMID:35256667

    Open questions at the time
    • Non-catalytic mechanism mechanistically undefined
    • USP44/UCHL5 redundancy not addressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How AXIN1's many roles (Wnt, c-Myc, NRF2, YAP/TAZ, IRF3, AMPK, neuronal arborization) are partitioned in a single cell and integrated with AXIN2 redundancy remains unresolved.
  • No unified model coordinating distinct AXIN1 complexes
  • Quantitative AXIN1 vs AXIN2 functional division incompletely mapped
  • Whether phase separation governs scaffolding broadly is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 4 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005829 cytosol 3 GO:0005886 plasma membrane 2 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 2
Partners
CTNNB1GSK3BIRF3NFE2L2PIN1PPP2R5APRKAA1YAP1
Complex memberships
c-Myc degradation complexβ-catenin destruction complex

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 AXIN1 encodes a scaffold protein that negatively regulates the Wnt pathway; adenovirus-mediated transfer of wild-type AXIN1 induced apoptosis in hepatocellular and colorectal cancer cells harboring APC, CTNNB1, or AXIN1 mutations, and AXIN1-mutant cells showed increased TCF/β-catenin nuclear DNA binding. Adenoviral gene transfer, TCF DNA-binding assay, sequencing of cancer cell lines and primary tumors Nature genetics High 10700176
2001 A missense mutation in the GSK3-binding domain of zebrafish Axin1 (masterblind allele) abolishes binding of Axin1 to GSK3 and impairs TCF-dependent transcription, causing fate transformation of telencephalon and eyes to diencephalon; overexpression of wild-type Axin1 or GSK3β rescued the phenotype. Genetic mapping, binding assay (GSK3/Axin1 interaction), TCF reporter assay, rescue by overexpression in zebrafish Genes & development High 11390362
2009 Axin1 scaffold protein facilitates formation of a c-Myc degradation complex containing GSK3β, Pin1, and PP2A-B56α; Axin1 knockdown decreases c-Myc association with these proteins, reduces T58 phosphorylation, enhances S62 phosphorylation, and increases c-Myc stability, while acute Axin1 expression reduces c-Myc levels and suppresses c-Myc transcriptional activity. Co-immunoprecipitation, siRNA knockdown, overexpression, phosphorylation assays The EMBO journal High 19131971
2010 The central region of Axin1 implicated in binding GSK3β and β-catenin is natively unfolded (intrinsically disordered), supporting a model in which the unfolded scaffold facilitates dynamic kinase-substrate interactions required for β-catenin phosphorylation. NMR, circular dichroism, analytical ultracentrifugation, and other biophysical methods Journal of molecular biology High 21087614
2012 Wnt signaling suppresses β-catenin ubiquitination within an intact Axin1 complex rather than causing complex disassembly or inhibiting phosphorylation of Axin1-bound β-catenin; β-catenin is phosphorylated, ubiquitinated, and degraded all within the intact Axin1 complex, and Wnt signaling leads to complex saturation by phospho-β-catenin, allowing newly synthesized free β-catenin to accumulate. Endogenous protein immunoprecipitation, mass spectrometry, proteasome inhibition, Wnt stimulation in colorectal cancer cells and primary intestinal epithelium Cell High 22682247
2012 Conditional hepatocyte-specific deletion of Axin1 in adult mice leads to acute hepatocyte proliferation, activation of a subset of Wnt target genes (Axin2, c-Myc, cyclin D1), but does not increase nuclear β-catenin or cause zonation changes typical of APC loss; 5/9 mice developed HCC after one year. Conditional Cre/loxP knockout, qRT-PCR, immunoprecipitation, histology, immunoblot Gastroenterology High 22960659
2011 Decreased AXIN1 expression and altered ratio of two naturally occurring AXIN1 splice variants in breast cancer contributes to increased c-Myc protein stability, altered S62/T58 phosphorylation balance, and increased oncogenic c-Myc activity. Splice variant quantification, siRNA knockdown, phosphorylation assays, primary breast cancer tissue analysis Proceedings of the National Academy of Sciences of the United States of America Medium 21808024
2014 Axin1 forms a physical complex with NRF2 (involving the central region of Axin1 and the Neh4/Neh5 domains of NRF2), and WNT-3A regulates this complex; Axin1 knockdown increases NRF2 protein levels; Axin1 stabilization with tankyrase inhibitors blocks WNT/NRF2 signaling; conditional hepatocyte-specific Axin1 deletion upregulates the NRF2 antioxidant signature. Co-immunoprecipitation, siRNA knockdown, conditional liver KO mice, tankyrase inhibitor treatment, reporter assays Antioxidants & redox signaling High 25336178
2017 TRIM65 E3 ubiquitin ligase directly binds Axin1 and promotes its ubiquitination and proteasomal degradation, thereby activating β-catenin signaling in hepatocellular carcinoma. Co-immunoprecipitation, ubiquitination assay, overexpression and knockdown with β-catenin readout, in vitro and in vivo Journal of cell science Medium 28754688
2020 USP44 deubiquitinase interacts with Axin1 and reduces its ubiquitination, thereby stabilizing Axin1 protein (without affecting Axin1 mRNA), suppressing β-catenin signaling, inhibiting proliferation, and promoting apoptosis in colorectal cancer cells. Co-immunoprecipitation, ubiquitination assay, overexpression and knockdown, Axin1 mRNA stability measurement Cell biology international Medium 32285989
2018 TRIM11 E3 ubiquitin ligase directly interacts with Axin1 (Co-IP) and promotes its ubiquitination and degradation, thereby activating β-catenin signaling in lymphoma cells. Co-immunoprecipitation, ubiquitination detection, overexpression and knockdown Experimental cell research Medium 31786079
2018 RNF146 E3 ubiquitin ligase promotes ubiquitination of Axin1, leading to its degradation and activation of β-catenin signaling in colorectal cancer. Co-immunoprecipitation, ubiquitination assay, knockdown and overexpression Biochemical and biophysical research communications Low 29932918
2011 Hsp90α/β associates with a complex containing GSK3β, axin1, β-catenin, and phospho-β-catenin in MCF-7 breast cancer cells; Hsp90 inhibition modulates β-catenin phosphorylation within this complex. Co-immunoprecipitation, confocal laser scanning microscopy, selective Hsp90 inhibition Biochemical and biophysical research communications Low 21925151
2010 MAP3K1 physically interacts with Axin1 in an interaction induced and modulated by Wnt stimulation; MAP3K1 E3 ubiquitin ligase activity (not kinase activity) is required for TCF/LEF-driven transcription and Wnt3A-driven endogenous gene expression. Immunoprecipitation-coupled proteomics (IP-MS), siRNA depletion, ubiquitin ligase vs kinase mutant analysis, TCF reporter assay Biological chemistry Medium 20128690
2016 γ-Protocadherin-C3 physically interacts with the DIX domain of Axin1 via its unique variable cytoplasmic domain; C3-VCD competes with Dishevelled for DIX domain binding, stabilizes Axin1 at the membrane, and reduces Lrp6 phosphorylation to inhibit Wnt signaling. Co-immunoprecipitation, competitive binding assay, Lrp6 phosphorylation assay, conditional transgenic in vivo Scientific reports Medium 27530555
2023 γ-Pcdh-C3 interacts with Axin1 in the cortex in vivo; loss of γC3 disrupts Axin1 localization to synaptic fractions and severely reduces dendritic complexity of cortical pyramidal neurons; rescue experiments in cultured neurons show γC3 promotes arborization through an Axin1-dependent mechanism mediated by the C3 variable cytoplasmic domain. In vivo co-IP from cortex, subcellular fractionation, CRISPR/Cas9 KO, rescue with domain deletion constructs, confocal imaging of dendrites The Journal of neuroscience High 36604170
2012 Axin1 (but not Axin2) plays an essential role in host defense against Salmonella; pathogenic Salmonella reduces Axin1 levels post-translationally through ubiquitination and SUMOylation involving the DIX domain and Ser614 of Axin1; loss of Axin1 increases bacterial invasiveness and inflammatory response in intestinal epithelial cells. Immunofluorescence, Western blotting, domain mapping (DIX domain and Ser614 mutants), ubiquitination/SUMOylation assays, siRNA knockdown PloS one Medium 22509369
2016 RUNX1 and estrogen receptor (ER) occupy adjacent regulatory elements in AXIN1's second intron; RUNX1 antagonizes estrogen/ER-mediated suppression of AXIN1 transcription; RUNX1 loss in ER+ mammary epithelial cells decreases AXIN1, increases β-catenin, deregulates mitosis, and stimulates proliferation; these effects are rescued by AXIN1 stabilization. ChIP, siRNA knockdown in vitro and conditional KO in vivo, RNA-seq, rescue experiments with AXIN1 stabilization Nature communications High 26916619
2016 Vitamin D receptor (VDR) transcriptionally regulates Axin1 expression via a genomic VDR binding site in the Axin1 regulatory region; VDR deletion reduces cytosolic Axin1 protein and mRNA; VDR and Axin1 do not physically interact. ChIP assay, conditional intestinal VDR KO mice, Western blot, RT-PCR, subcellular fractionation, cycloheximide/actinomycin chase, immunohistochemistry The Journal of steroid biochemistry and molecular biology Medium 27601169
2015 Axin1 knockdown in satellite cells (skeletal muscle stem cells) suppresses proliferation and promotes premature myogenic differentiation; simultaneous knockdown of Axin1 and β-catenin rescues proliferation and partially prevents premature differentiation, placing Axin1 function upstream of β-catenin in muscle stem cell regulation; Axin1 and Axin2 are not fully redundant in satellite cells. siRNA knockdown, retroviral overexpression, Axin2-null mouse satellite cells, TCF reporter assay, immunofluorescence for nuclear β-catenin Cellular signalling Medium 25866367
2016 Axin-1 localizes around the meiotic spindle in mouse oocytes; Axin1 siRNA knockdown causes defective spindles, misaligned chromosomes, failure of first polar body extrusion, impaired pronuclear formation, and loss of γ-tubulin/Nek9 at spindle poles with retention of BubR1 at kinetochores. Immunofluorescence localization, siRNA microinjection into oocytes, spindle assembly checkpoint analysis PloS one Medium 27284927
2017 In tankyrase inhibitor-treated colorectal cancer cells, AXIN1 is not required for degradasome (β-catenin destruction complex assembly) formation, whereas AXIN2 depletion substantially impairs both degradasome formation and its capacity to degrade β-catenin. siRNA depletion, tankyrase inhibitor (G007-LK) treatment, fluorescence microscopy of degradasomes, β-catenin degradation assay PloS one Medium 28107521
2018 Peptide microarray mapping of the AXIN1 intrinsically disordered region identified multiple binding epitopes for CK1ε, c-Myc, Pin1, and p53; AXIN1 competes with Dishevelled (DVL) for CK1ε binding and regulates CK1ε-induced DVL phosphorylation and Wnt/β-catenin activation, validated with epitope-mimicking peptides and short deletion variants. Peptide microarray, in vitro binding assay, epitope-mimicking peptide competition, AXIN1 deletion variants, phosphorylation assay The Journal of biological chemistry Medium 30166345
2018 C9orf140, identified by tandem-affinity purification and mass spectrometry as an Axin1-interacting protein, negatively regulates Wnt/β-catenin signaling by outcompeting PP2A for Axin1 binding, thereby shifting the balance toward β-catenin phosphorylation and preventing Wnt3A-induced β-catenin accumulation; Wnt-induced C9orf140 expression via β-catenin creates a negative feedback loop. TAP-MS, Co-immunoprecipitation, competitive binding assay, zebrafish validation, reporter assay Oncogene Medium 29531269
2019 AXIN1 deletion cooperates with c-Met activation to induce hepatocellular carcinoma in mice in a β-catenin-dependent but Notch-independent manner; genetic deletion of β-catenin completely prevented HCC development in c-Met/sgAxin1 mice, whereas blocking Notch via dominant-negative RBP-J or Notch2 ablation had no effect. CRISPR/Cas9 gene deletion in vivo, hydrodynamic transposition, conditional Ctnnb1 KO, dominant-negative RBP-J, Notch2 KO, gene expression analysis Hepatology High 30737831
2022 AXIN1 binds to YAP/TAZ in human HCC cells and regulates YAP/TAZ stability; deletion of Axin1 strongly induces nuclear YAP/TAZ; concomitant Yap and Taz deletion significantly inhibits c-Met/sgAxin1-driven HCC, identifying YAP/TAZ as major downstream effectors of AXIN1 loss-driven hepatocarcinogenesis. Co-immunoprecipitation, conditional YAP/TAZ KO in vivo, inducible CreERT2 system, tumor growth assays, tankyrase inhibitor combination treatment Hepatology Medium 35921500
2022 SIRT4 translocates from mitochondria to the cytoplasm upon Wnt stimulation and deacetylates Axin1 at K147 (within the RGS domain); K147 acetylation in resting cells maintains the destruction complex; the Axin1-K147R mutant impairs β-TrCP assembly into the destruction complex, leading to β-catenin accumulation even without Wnt stimulation. Acetylation assay, SIRT4 overexpression and KD, site-directed mutagenesis (K147R), subcellular fractionation, Co-IP Frontiers in oncology Medium 35707358
2024 Hypoxia induces lactylation of Axin1 protein at K147, which promotes its ubiquitination and proteasomal degradation, thereby relieving Axin1-mediated suppression of glycolysis and cell stemness in esophageal carcinoma cells; Axin1-K147 mutant resistant to lactylation reverses these effects. Pan-lysine lactylation mass spectrometry, site-directed mutagenesis (K147), ubiquitination assay, ECAR/glucose/lactate measurements, in vivo tumor growth Biochemical pharmacology Medium 38972426
2024 AXIN1 stabilizes the antiviral transcription factor IRF3 by recruiting USP35, which removes K48-linked ubiquitination at IRF3 K366, preventing p62-mediated autophagic degradation; upon virus infection, TBK1-phosphorylated AXIN1 undergoes phase separation, increasing IRF3 phosphorylation and IFN-I production; KYA1797K (binding AXIN1 RGS domain) enhances AXIN1-IRF3 interaction. Co-immunoprecipitation, ubiquitination assay (K48-linkage specific), autophagic flux assay, phase separation imaging, TBK1 phosphorylation assay, pharmacological RGS-domain ligand Signal transduction and targeted therapy High 39384753
2024 Analysis of 80 tumor-associated AXIN1 missense variants identified 18 that significantly activate β-catenin signaling; most loss-of-function missense mutations lose binding to the interaction partner corresponding to the mutated domain (GSK3β, β-catenin, or RGS/APC binding domains); truncated AXIN1 proteins inversely correlate with β-catenin regulatory function. Co-immunoprecipitation for each domain-specific binding partner, β-catenin reporter assay, structural prediction analysis for 80 variants Cancer research High 38359148
2019 AXIN1 forms a complex with AMPK and LKB1 in skeletal muscle during contraction; contraction and AMPK activation upregulate total Axin1 protein; Axin1 knockdown reduces AMPK activation, GTP-loading of Rac1, PAK phosphorylation, and contraction-stimulated glucose uptake in C2C12 myotubes, defining an AMPK/Axin1-Rac1 signaling axis. Reciprocal co-immunoprecipitation from myotubes and mouse muscle, siRNA knockdown, AMPK activator treatment, glucose uptake assay, GTP-Rac1 pull-down American journal of physiology. Endocrinology and metabolism Medium 31846370
2021 In skeletal muscle-specific AXIN1 knockout mice, AXIN1 deletion does not affect AMPK/mTORC1 signaling or glucose uptake at rest or during contraction/exercise under most conditions, with the only difference being elevated α2/β2/γ3 AMPK activity and AMP/ATP ratio in gastrocnemius during exercise (likely due to AXIN2 functional redundancy). Tamoxifen-inducible muscle-specific KO, AMPK/mTORC1 phosphorylation assays, glucose uptake assay, exercise protocols, AMP/ATP measurement The Journal of physiology Medium 33913171
2022 UCHL5 deubiquitinase physically interacts with multiple domains of Axin1 and is required for both stabilization and polymerization of Axin1 proteins; these events are governed by deubiquitination in the DIX domain of Axin1 but do not require the catalytic deubiquitinating activity of UCHL5. Co-immunoprecipitation, Axin1 domain-binding assays, Axin1 polymerization assay, catalytic UCHL5 mutant analysis, β-catenin reporter assay Scientific reports Medium 35256667
2022 Axin1 is required for IFN-γ/Th1-mediated intestinal immune program; intestinal epithelial Axin1 deficiency renders mice more susceptible to chemically induced colon carcinogenesis but reduces DSS-induced colitis; Axin1 has redundant function with Axin2 for Wnt pathway down-regulation in the intestine. Intestinal epithelial-specific Axin1 KO, Axin2 KO, chemically induced tumorigenesis, DSS colitis, RNA-seq Cellular and molecular gastroenterology and hepatology Medium 36356835
2022 Axin-1 C-terminal region (710-797 aa) binds the N-terminal region (1-100 aa) of Caveolin-1; disruption of this interaction by CRISPR/Cas9 increases TNF-α and IL-6 production and reduces β-catenin in alveolar type I cells challenged with LPS; Axin-1 functions as an adaptor for Caveolin-1 in regulating inflammatory cytokine production. Yeast two-hybrid screening, co-immunoprecipitation with domain mapping, CRISPR/Cas9 disruption, cytokine ELISA Biochemical and biophysical research communications Medium 30954225
2020 YTHDF2 RNA m6A reader promotes AXIN1 mRNA decay, thereby activating Wnt/β-catenin signaling in lung adenocarcinoma; knockout of AXIN1 rescues the inhibitory effect of YTHDF2 depletion on lung cancer cell proliferation, colony-formation, and migration. RNA-seq, m6A-seq, CLIP-seq, RIP-seq, mRNA stability assay, AXIN1 KO rescue experiment Cell death & disease Medium 33980824
2022 Deletion of Axin1 in condylar chondrocytes at adult stage causes OA-like degeneration associated with activation of both β-catenin and FGF/ERK1/2 signaling; increased Fgfr1 expression, MMP13 and Adamts5, and decreased lubricin were detected; both pathways cooperatively contribute to cartilage degeneration. Conditional tamoxifen-inducible chondrocyte KO, immunostaining, qRT-PCR, histomorphometry Journal of cellular physiology Medium 30070692
2022 Specific deletion of Axin1 in limb mesenchymal cells activates both β-catenin and BMP signaling, leading to fibular hemimelia-like phenotype; inhibition of either β-catenin or BMP signaling significantly reverses the FH phenotype, demonstrating that Axin1 controls limb development through integration of both pathways. Conditional limb mesenchyme Axin1 KO, pharmacological β-catenin and BMP inhibition, in vivo rescue eLife High 36541713

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 AXIN1 mutations in hepatocellular carcinomas, and growth suppression in cancer cells by virus-mediated transfer of AXIN1. Nature genetics 865 10700176
2012 Wnt signaling through inhibition of β-catenin degradation in an intact Axin1 complex. Cell 739 22682247
2002 Mutational spectrum of beta-catenin, AXIN1, and AXIN2 in hepatocellular carcinomas and hepatoblastomas. Oncogene 398 12101426
2001 A mutation in the Gsk3-binding domain of zebrafish Masterblind/Axin1 leads to a fate transformation of telencephalon and eyes to diencephalon. Genes & development 219 11390362
2006 Differential effects of inactivated Axin1 and activated beta-catenin mutations in human hepatocellular carcinomas. Oncogene 205 16964294
2001 Deletions of AXIN1, a component of the WNT/wingless pathway, in sporadic medulloblastomas. Cancer research 189 11585731
2012 Wnt/β-catenin signaling and AXIN1 regulate apoptosis triggered by inhibition of the mutant kinase BRAFV600E in human melanoma. Science signaling 139 22234612
2021 A novel protein AXIN1-295aa encoded by circAXIN1 activates the Wnt/β-catenin signaling pathway to promote gastric cancer progression. Molecular cancer 133 34863211
2014 AXIN1 and AXIN2 variants in gastrointestinal cancers. Cancer letters 116 25236910
2003 AXIN1 mutations but not deletions in cerebellar medulloblastomas. Oncogene 113 12555076
2009 The Axin1 scaffold protein promotes formation of a degradation complex for c-Myc. The EMBO journal 98 19131971
2021 RNA m6A reader YTHDF2 facilitates lung adenocarcinoma cell proliferation and metastasis by targeting the AXIN1/Wnt/β-catenin signaling. Cell death & disease 92 33980824
2006 Increased DNA methylation at the AXIN1 gene in a monozygotic twin from a pair discordant for a caudal duplication anomaly. American journal of human genetics 86 16773576
2007 Wnt/Axin1/beta-catenin signaling regulates asymmetric nodal activation, elaboration, and concordance of CNS asymmetries. Neuron 81 17678853
2011 Mechanistic insight into Myc stabilization in breast cancer involving aberrant Axin1 expression. Proceedings of the National Academy of Sciences of the United States of America 73 21808024
2007 Axin1 and Axin2 are regulated by TGF- and mediate cross-talk between TGF- and Wnt signaling pathways. Annals of the New York Academy of Sciences 66 18083923
2016 RUNX1 prevents oestrogen-mediated AXIN1 suppression and β-catenin activation in ER-positive breast cancer. Nature communications 64 26916619
2001 Identification of AXUD1, a novel human gene induced by AXIN1 and its reduced expression in human carcinomas of the lung, liver, colon and kidney. Oncogene 61 11526492
2003 Detection of point mutations of the Axin1 gene in colorectal cancers. International journal of cancer 59 14566817
2017 TRIM65 triggers β-catenin signaling via ubiquitylation of Axin1 to promote hepatocellular carcinoma. Journal of cell science 57 28754688
2015 5-hydroxytryptamine receptor (5-HT1DR) promotes colorectal cancer metastasis by regulating Axin1/β-catenin/MMP-7 signaling pathway. Oncotarget 57 26214021
2017 Loss of AXIN1 drives acquired resistance to WNT pathway blockade in colorectal cancer cells carrying RSPO3 fusions. EMBO molecular medicine 56 28100566
2014 WNT-3A regulates an Axin1/NRF2 complex that regulates antioxidant metabolism in hepatocytes. Antioxidants & redox signaling 55 25336178
2018 MicroRNA-128 Protects Dopamine Neurons from Apoptosis and Upregulates the Expression of Excitatory Amino Acid Transporter 4 in Parkinson's Disease by Binding to AXIN1. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 53 30537735
2015 Coordinated action of Axin1 and Axin2 suppresses β-catenin to regulate muscle stem cell function. Cellular signalling 51 25866367
2010 Critical scaffolding regions of the tumor suppressor Axin1 are natively unfolded. Journal of molecular biology 51 21087614
2010 Histone modifications at the blastocyst Axin1(Fu) locus mark the heritability of in vitro culture-induced epigenetic alterations in mice. Biology of reproduction 50 20650886
2012 Conditional disruption of Axin1 leads to development of liver tumors in mice. Gastroenterology 49 22960659
2019 Axis inhibition protein 1 (Axin1) Deletion-Induced Hepatocarcinogenesis Requires Intact β-Catenin but Not Notch Cascade in Mice. Hepatology (Baltimore, Md.) 47 30737831
2020 The RNA-binding protein RBM47 inhibits non-small cell lung carcinoma metastasis through modulation of AXIN1 mRNA stability and Wnt/β-catentin signaling. Surgical oncology 46 32891348
2020 LncRNA NEAT1 Regulates the Development of Parkinson's Disease by Targeting AXIN1 Via Sponging miR-212-3p. Neurochemical research 43 33241432
2020 USP44 suppresses proliferation and enhances apoptosis in colorectal cancer cells by inactivating the Wnt/β-catenin pathway via Axin1 deubiquitination. Cell biology international 42 32285989
2020 HIF-1α/microRNA-128-3p axis protects hippocampal neurons from apoptosis via the Axin1-mediated Wnt/β-catenin signaling pathway in Parkinson's disease models. Aging 40 32167488
2016 The γ-Protocadherin-C3 isoform inhibits canonical Wnt signalling by binding to and stabilizing Axin1 at the membrane. Scientific reports 40 27530555
2017 Differential Roles of AXIN1 and AXIN2 in Tankyrase Inhibitor-Induced Formation of Degradasomes and β-Catenin Degradation. PloS one 37 28107521
2016 WDR26 is a new partner of Axin1 in the canonical Wnt signaling pathway. FEBS letters 35 27098453
2024 Hypoxia exposure induces lactylation of Axin1 protein to promote glycolysis of esophageal carcinoma cells. Biochemical pharmacology 33 38972426
2008 Mutations in the AXIN1 gene in advanced prostate cancer. European urology 33 18514389
2022 YTHDF2 interference suppresses the EMT of cervical cancer cells and enhances cisplatin chemosensitivity by regulating AXIN1. Drug development research 32 35489084
2024 The scaffold protein AXIN1: gene ontology, signal network, and physiological function. Cell communication and signaling : CCS 31 38291457
2021 MicroRNAs sequencing of plasma exosomes derived from patients with atrial fibrillation: miR-124-3p promotes cardiac fibroblast activation and proliferation by regulating AXIN1. Journal of physiology and biochemistry 31 34495485
2017 Axin1 up-regulated 1 accelerates stress-induced cardiomyocytes apoptosis through activating Wnt/β-catenin signaling. Experimental cell research 30 28830684
2010 MAP3K1 functionally interacts with Axin1 in the canonical Wnt signalling pathway. Biological chemistry 30 20128690
2021 Evaluation of AXIN1 and AXIN2 as targets of tankyrase inhibition in hepatocellular carcinoma cell lines. Scientific reports 29 33811251
2019 TRIM11 promotes lymphomas by activating the β-catenin signaling and Axin1 ubiquitination degradation. Experimental cell research 28 31786079
2018 The E3 ubiquitin ligase RNF146 promotes colorectal cancer by activating the Wnt/β-catenin pathway via ubiquitination of Axin1. Biochemical and biophysical research communications 28 29932918
2011 Hsp90α/β associates with the GSK3β/axin1/phospho-β-catenin complex in the human MCF-7 epithelial breast cancer model. Biochemical and biophysical research communications 28 21925151
2020 Inhibition of Axin1 in osteoblast precursor cells leads to defects in postnatal bone growth through suppressing osteoclast formation. Bone research 27 32821442
2019 Down-regulation of microRNA-31-5p inhibits proliferation and invasion of osteosarcoma cells through Wnt/β-catenin signaling pathway by enhancing AXIN1. Experimental and molecular pathology 27 30844369
2012 Axin1 prevents Salmonella invasiveness and inflammatory response in intestinal epithelial cells. PloS one 27 22509369
2019 An AMPK/Axin1-Rac1 signaling pathway mediates contraction-regulated glucose uptake in skeletal muscle cells. American journal of physiology. Endocrinology and metabolism 26 31846370
2018 Deletion of Axin1 in condylar chondrocytes leads to osteoarthritis-like phenotype in temporomandibular joint via activation of β-catenin and FGF signaling. Journal of cellular physiology 26 30070692
2004 Frequent loss of the AXIN1 locus but absence of AXIN1 gene mutations in adenocarcinomas of the gastro-oesophageal junction with nuclear beta-catenin expression. British journal of cancer 26 14970870
2011 Generation of Axin1 conditional mutant mice. Genesis (New York, N.Y. : 2000) 25 21344612
2018 miR-155 Is Downregulated in Familial Adenomatous Polyposis and Modulates WNT Signaling by Targeting AXIN1 and TCF4. Molecular cancer research : MCR 24 30072583
2011 Clinicopathological analysis of β-catenin and Axin-1 in solid pseudopapillary neoplasms of the pancreas. Annals of surgical oncology 24 21769465
2022 Differential requirement of Hippo cascade during CTNNB1 or AXIN1 mutation-driven hepatocarcinogenesis. Hepatology (Baltimore, Md.) 23 35921500
2022 Axin1 Protects Colon Carcinogenesis by an Immune-Mediated Effect. Cellular and molecular gastroenterology and hepatology 22 36356835
2023 A Unique Role for Protocadherin γC3 in Promoting Dendrite Arborization through an Axin1-Dependent Mechanism. The Journal of neuroscience : the official journal of the Society for Neuroscience 21 36604170
2020 The Synthetic Small Molecule FL3 Combats Intestinal Tumorigenesis via Axin1-Mediated Inhibition of Wnt/β-Catenin Signaling. Cancer research 21 32665357
2024 Cancer-associated fibroblasts-secreted exosomal miR-92a-3p promotes tumor growth and stemness in hepatocellular carcinoma through activation of Wnt/β-catenin signaling pathway by suppressing AXIN1. Journal of cellular physiology 20 38949237
2018 Genomic convergence of locus-based GWAS meta-analysis identifies AXIN1 as a novel Parkinson's gene. Immunogenetics 20 29923028
2016 Vitamin D receptor is a novel transcriptional regulator for Axin1. The Journal of steroid biochemistry and molecular biology 20 27601169
2013 Alterations of axis inhibition protein 1 (AXIN1) in hepatitis B virus-related hepatocellular carcinoma and overexpression of AXIN1 induces apoptosis in hepatocellular cancer cells. Oncology research 20 23879168
2021 UBE3C promotes proliferation and inhibits apoptosis by activating the β-catenin signaling via degradation of AXIN1 in gastric cancer. Carcinogenesis 19 32930707
2013 CTNNB1, AXIN1 and APC expression analysis of different medulloblastoma variants. Clinics (Sao Paulo, Brazil) 19 23525311
2006 Verification of predicted alternatively spliced Wnt genes reveals two new splice variants (CTNNB1 and LRP5) and altered Axin-1 expression during tumour progression. BMC genomics 19 16772034
2015 The variations in the AXIN1 gene and susceptibility to cryptorchidism. Journal of pediatric urology 18 25802106
2009 Changes of AXIN-1 and beta-catenin in neuroepithelial brain tumors. Pathology oncology research : POR 18 19633924
2024 AXIN1 boosts antiviral response through IRF3 stabilization and induced phase separation. Signal transduction and targeted therapy 17 39384753
2018 C9orf140, a novel Axin1-interacting protein, mediates the negative feedback loop of Wnt/β-catenin signaling. Oncogene 17 29531269
2017 Relationship between RUNX1 and AXIN1 in ER-negative versus ER-positive Breast Cancer. Cell cycle (Georgetown, Tex.) 17 28055379
2022 The E3 Ubiquitin Ligase TRIM11 Facilitates Gastric Cancer Progression by Activating the Wnt/β-Catenin Pathway via Destabilizing Axin1 Protein. Journal of oncology 16 35237324
2021 miR-3574 ameliorates intermittent hypoxia-induced cardiomyocyte injury through inhibiting Axin1. Aging 16 33582657
2016 Axin-1 Regulates Meiotic Spindle Organization in Mouse Oocytes. PloS one 15 27284927
2003 Mutation analysis of CTNNB1 (beta-catenin) and AXIN1, the components of Wnt pathway, in cervical carcinomas. Oncology reports 15 12883680
2024 Analysis of Tumor-Associated AXIN1 Missense Mutations Identifies Variants That Activate β-Catenin Signaling. Cancer research 14 38359148
2022 SIRT4-Catalyzed Deacetylation of Axin1 Modulates the Wnt/β-Catenin Signaling Pathway. Frontiers in oncology 14 35707358
2020 TRIM32 triggers β-catenin signaling through ubiquitylation of AXIN1 to promote inflammatory factor-induced apoptosis of rat nucleus pulposus cells. American journal of physiology. Cell physiology 14 31967859
2019 MicroRNA-1181 supports the growth of hepatocellular carcinoma by repressing AXIN1. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 14 31514071
2024 UBE2N promotes cell viability and glycolysis by promoting Axin1 ubiquitination in prostate cancer cells. Biology direct 13 38715121
2023 Tripartite motif 31 drives gastric cancer cell proliferation and invasion through activating the Wnt/β-catenin pathway by regulating Axin1 protein stability. Scientific reports 13 37973999
2022 TRIM46 upregulates Wnt/β-catenin signaling by inhibiting Axin1 to mediate hypoxia-induced epithelial-mesenchymal transition in HK2 cells. Molecular and cellular biochemistry 13 35670901
2021 AXIN1 knockout does not alter AMPK/mTORC1 regulation and glucose metabolism in mouse skeletal muscle. The Journal of physiology 13 33913171
2018 Analysis of binding interfaces of the human scaffold protein AXIN1 by peptide microarrays. The Journal of biological chemistry 13 30166345
2000 Identification of novel polymorphisms in the AXIN1++ and CDX-2 genes. Journal of human genetics 13 10944858
2023 TRIM37 promotes gallbladder cancer proliferation by activating the Wnt/β-catenin pathway via ubiquitination of Axin1. Translational oncology 12 37379772
2022 UCHL5 controls β-catenin destruction complex function through Axin1 regulation. Scientific reports 12 35256667
2021 Targeting TRIM54/Axin1/β-Catenin Axis Prohibits Proliferation and Metastasis in Hepatocellular Carcinoma. Frontiers in oncology 12 34956880
2020 Axin1 inhibits proliferation, invasion, migration and EMT of hepatocellular carcinoma by targeting miR-650. American journal of translational research 12 32269738
2019 Axin-1 binds to Caveolin-1 to regulate the LPS-induced inflammatory response in AT-I cells. Biochemical and biophysical research communications 12 30954225
2019 Stimulation of endothelial progenitor cells by microRNA-31a-5p to induce endothelialization in an aneurysm neck after coil embolization by modulating the Axin1-mediated β-catenin/vascular endothelial growth factor pathway. Journal of neurosurgery 12 31398705
2017 AXIN1 protects against testicular germ cell tumors via the PI3K/AKT/mTOR signaling pathway. Oncology letters 12 28693262
2022 Axin1: A novel scaffold protein joins the antiviral network of interferon. Molecular microbiology 11 36308071
2022 Specific deletion of Axin1 leads to activation of β-catenin/BMP signaling resulting in fibular hemimelia phenotype in mice. eLife 11 36541713
2016 AXIN1 Expression and Localization in Meningiomas and Association to Changes of APC and E-cadherin. Anticancer research 11 27630299
2014 Association between polymorphisms in AXIN1 gene and atrial septal defect. Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals 11 25355064
2005 Infrequent mutation of APC, AXIN1, and GSK3B in human pituitary adenomas with abnormal accumulation of CTNNB1. Journal of neuro-oncology 11 15981102
2021 LncDBH-AS1 knockdown enhances proliferation of non-small cell lung cancer cells by activating the Wnt signaling pathway via the miR-155/AXIN1 axis. European review for medical and pharmacological sciences 10 33506901
2020 Long-Term Inhibition of Notch in A-375 Melanoma Cells Enhances Tumor Growth Through the Enhancement of AXIN1, CSNK2A3, and CEBPA2 as Intermediate Genes in Wnt and Notch Pathways. Frontiers in oncology 10 32695658

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