Affinage

AXIN1

Axin-1 · UniProt O15169

Length
862 aa
Mass
95.6 kDa
Annotated
2026-04-28
100 papers in source corpus 33 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AXIN1 is a multi-domain scaffold protein that serves as the concentration-limiting core of the β-catenin destruction complex, coordinating the phosphorylation, ubiquitination, and proteasomal degradation of β-catenin to suppress canonical Wnt signaling (PMID:22682247, PMID:10700176). Its central intrinsically disordered region positions GSK3β, CK1ε, APC, β-TrCP, and PP2A on the same platform, with acetylation at K147 regulating β-TrCP recruitment and lactylation at the same residue promoting AXIN1 degradation under hypoxia (PMID:21087614, PMID:35707358, PMID:38972426). Beyond Wnt suppression, AXIN1 scaffolds a GSK3β/Pin1/PP2A complex that destabilizes c-Myc, interacts with NRF2 to restrain antioxidant gene expression, binds YAP/TAZ to control Hippo pathway output, and recruits USP35 to stabilize IRF3 for type I interferon production through TBK1-triggered phase separation (PMID:19131971, PMID:25336178, PMID:35921500, PMID:39384753). Loss-of-function mutations in AXIN1 are recurrently found in hepatocellular carcinoma, where conditional deletion cooperates with c-Met to drive β-catenin- and YAP/TAZ-dependent tumorigenesis (PMID:10700176, PMID:30737831, PMID:35921500).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2000 High

    Establishing AXIN1 as a Wnt pathway tumor suppressor: AXIN1 mutations in HCC activated β-catenin/TCF signaling, and wild-type AXIN1 re-expression induced apoptosis in cancer cells, answering whether AXIN1 loss-of-function causally drives oncogenic Wnt activation.

    Evidence Adenoviral AXIN1 re-expression in HCC and CRC cell lines with mutation sequencing

    PMID:10700176

    Open questions at the time
    • Mechanism by which AXIN1 loss activates β-catenin not yet defined at the biochemical level
    • Cooperative genetic events for tumorigenesis unknown
  2. 2001 High

    Defining the functional requirement for the AXIN1-GSK3β interaction: a missense mutation in the GSK3-binding domain of zebrafish Axin1 abolished GSK3 binding and disrupted anterior neural patterning, demonstrating that the scaffold-kinase interaction is essential for pathway activity in vivo.

    Evidence Zebrafish masterblind allele genetic epistasis with overexpression rescue

    PMID:11390362

    Open questions at the time
    • Whether the same domain requirements hold in mammalian systems
    • Structural basis of the AXIN1-GSK3β interface at atomic resolution
  3. 2009 High

    Revealing a non-Wnt scaffold function: AXIN1 organizes a GSK3β/Pin1/PP2A-B56α complex that directs sequential phosphorylation and degradation of c-Myc, showing AXIN1 is not exclusively a Wnt pathway component but a general degradation scaffold.

    Evidence Co-IP, siRNA knockdown, phospho-specific immunoblotting, c-Myc stability assays in multiple cell lines

    PMID:19131971 PMID:21808024

    Open questions at the time
    • Whether AXIN1-mediated c-Myc degradation operates through the same physical complex as β-catenin destruction
    • Identity of the E3 ligase acting on c-Myc within this complex
  4. 2010 High

    Characterizing the structural basis of scaffold flexibility: biophysical analysis revealed that the central GSK3β/β-catenin-binding region of AXIN1 is intrinsically disordered, explaining how a single scaffold can dynamically accommodate multiple binding partners.

    Evidence NMR, CD spectroscopy, size-exclusion chromatography on purified AXIN1 fragments

    PMID:21087614

    Open questions at the time
    • Full-length AXIN1 structural model not available
    • How disorder-to-order transitions influence binding partner selectivity
  5. 2012 High

    Redefining destruction complex mechanism: β-catenin phosphorylation, ubiquitination, and degradation all occur within an intact AXIN1 complex; Wnt blocks ubiquitination rather than disassembling the complex, causing saturation that allows free β-catenin accumulation — overturning the prevailing dissociation model.

    Evidence Quantitative mass spectrometry at endogenous levels, immunoprecipitation, proteasome inhibitor assays in primary intestinal epithelium and CRC lines

    PMID:22682247

    Open questions at the time
    • Identity of the E3 ligase inhibited by Wnt within the intact complex
    • Stoichiometric details of complex saturation kinetics
  6. 2012 High

    Demonstrating in vivo consequences of AXIN1 loss in liver: conditional Axin1 deletion in adult hepatocytes caused acute proliferation, Wnt target gene activation, and eventual HCC without nuclear β-catenin accumulation, distinguishing AXIN1-loss phenotype from APC-loss.

    Evidence Conditional Cre/loxP Axin1 KO mouse with transcriptional and histological analysis

    PMID:22960659

    Open questions at the time
    • Mechanism by which Wnt target genes activate without detectable nuclear β-catenin
    • Cooperative oncogenic hits required for full HCC penetrance
  7. 2014 High

    Identifying a non-canonical AXIN1-NRF2 axis: AXIN1 physically binds NRF2 and restrains its protein levels; liver-specific Axin1 KO mice upregulated the NRF2 antioxidant transcriptional signature, establishing AXIN1 as a regulator of redox metabolism independent of classical Wnt targets.

    Evidence Co-IP domain mapping, siRNA, tankyrase inhibition, conditional liver-specific KO mice

    PMID:25336178

    Open questions at the time
    • Whether AXIN1 promotes NRF2 degradation through Keap1 or an independent mechanism
    • Physiological significance of NRF2 dysregulation in AXIN1-mutant tumors
  8. 2016 High

    Uncovering transcriptional control of AXIN1: VDR directly binds the AXIN1 genomic locus and maintains cytosolic AXIN1 expression, while RUNX1 antagonizes estrogen-mediated AXIN1 suppression through an intronic regulatory element, revealing dual transcriptional inputs governing AXIN1 abundance.

    Evidence ChIP, conditional VDR KO mouse, RNA-seq, AXIN1 stabilization rescue in ER+ mammary cells

    PMID:26916619 PMID:27601169

    Open questions at the time
    • How VDR and RUNX1 regulatory elements integrate quantitatively
    • Whether other transcription factors regulate AXIN1 in non-epithelial tissues
  9. 2016 High

    Identifying membrane-tethering partners: γ-Protocadherin-C3 competes with Dishevelled for the AXIN1 DIX domain, stabilizing AXIN1 at the membrane and inhibiting Wnt signaling — later confirmed in vivo where γC3 loss disrupts AXIN1 synaptic localization and dendritic arborization in cortical neurons.

    Evidence Reciprocal Co-IP, domain competition, conditional transgenic mice; CRISPR KO mouse with subcellular fractionation and neuron rescue

    PMID:27530555 PMID:36604170

    Open questions at the time
    • Whether γC3-AXIN1 interaction modulates Wnt signaling specifically at synapses
    • Structural basis of DIX domain competition between γC3 VCD and Dishevelled
  10. 2017 Medium

    Identifying E3 ligases that target AXIN1 for degradation: TRIM65 and later TRIM11 were shown to ubiquitinate AXIN1 and promote its proteasomal degradation, activating β-catenin signaling in HCC and lymphoma respectively, establishing ubiquitin-mediated turnover as a major regulatory layer for AXIN1 protein levels.

    Evidence Co-IP, ubiquitination assays, overexpression/knockdown with in vivo xenograft (TRIM65); Co-IP and ubiquitination assay with functional readouts (TRIM11)

    PMID:28754688 PMID:31786079

    Open questions at the time
    • Whether TRIM65 and TRIM11 compete or cooperate for AXIN1 ubiquitination
    • Specific ubiquitin chain types attached by each E3
    • Independent replication in additional cancer types
  11. 2019 Medium

    Establishing AXIN1's role outside canonical Wnt contexts: AXIN1 complexes with AMPK in contracting skeletal muscle to activate Rac1 and glucose uptake, and binds Caveolin-1 in alveolar epithelial cells to restrain inflammatory cytokine production, broadening AXIN1's functional scope to metabolism and innate immunity.

    Evidence Reciprocal Co-IP in C2C12 myotubes and mouse exercise model; yeast two-hybrid and CRISPR disruption in alveolar cells

    PMID:30954225 PMID:31846370

    Open questions at the time
    • Mechanism by which AXIN1-AMPK activates Rac1 GTP loading
    • Whether these non-Wnt roles depend on the destruction complex or operate independently
  12. 2019 High

    Genetic epistasis confirming β-catenin dependence of AXIN1-loss HCC: Axin1 deletion cooperates with c-Met to drive HCC that is abolished by co-deletion of Ctnnb1 but unaffected by Notch pathway blockade, definitively placing β-catenin as the critical effector downstream of AXIN1 loss in liver cancer.

    Evidence CRISPR/Cas9 Axin1 deletion combined with liver-specific Ctnnb1 KO and dominant-negative Notch2 ablation in mouse HCC model

    PMID:30737831

    Open questions at the time
    • Whether β-catenin-independent pathways contribute at later stages of tumor evolution
    • Therapeutic exploitability of β-catenin dependence
  13. 2020 Medium

    Identifying deubiquitinases that stabilize AXIN1: USP44 directly deubiquitinates AXIN1 to stabilize its protein levels and suppress Wnt signaling; separately, UCHL5 stabilizes and promotes AXIN1 polymerization through a non-catalytic mechanism mediated by the DIX domain.

    Evidence Co-IP, ubiquitination assays, catalytically-dead UCHL5 mutant, AXIN1 polymerization assay, functional rescue

    PMID:32285989 PMID:35256667

    Open questions at the time
    • Whether USP44 and UCHL5 target different ubiquitin chain types on AXIN1
    • How non-catalytic UCHL5 function promotes DIX-dependent polymerization mechanistically
  14. 2022 High

    Revealing AXIN1 as a Hippo pathway regulator: AXIN1 binds YAP/TAZ and controls their stability; co-deletion of Yap/Taz significantly suppresses AXIN1-loss-driven HCC, identifying YAP/TAZ as major effectors beyond β-catenin in AXIN1-mutant liver cancer.

    Evidence Co-IP in human HCC cells, conditional Yap/Taz KO epistasis in Axin1-deleted mouse liver tumors

    PMID:35921500

    Open questions at the time
    • Mechanism by which AXIN1 promotes YAP/TAZ degradation (Hippo kinases vs. direct ubiquitination)
    • Relative contributions of β-catenin vs. YAP/TAZ to distinct tumor phenotypes
  15. 2022 Medium

    Identifying acetylation as a destruction complex regulatory switch: SIRT4 deacetylates AXIN1 at K147, and a K147R acetylation-mimicking mutant impairs β-TrCP recruitment, causing β-catenin accumulation — demonstrating that a single PTM site on AXIN1 controls destruction complex competence.

    Evidence SIRT4 translocation imaging, in vitro deacetylation assay, K147R mutagenesis with β-TrCP Co-IP

    PMID:35707358

    Open questions at the time
    • Identity of the acetyltransferase that modifies K147
    • Whether K147 acetylation and lactylation are mutually exclusive regulatory events
  16. 2024 High

    Systematic variant-function mapping: analysis of 80 tumor-associated AXIN1 missense variants revealed that 18 significantly impair β-catenin regulation with domain-specific loss of partner binding, providing a functional atlas of clinically relevant AXIN1 mutations.

    Evidence Systematic β-catenin signaling reporter assay and Co-IP of 80 variants with structural analysis

    PMID:38359148

    Open questions at the time
    • Whether variants affecting NRF2 or YAP/TAZ binding exist among uncharacterized mutations
    • Correlation with patient outcomes for functionally classified variants
  17. 2024 High

    Establishing AXIN1 in innate antiviral defense: AXIN1 recruits USP35 to remove K48-linked ubiquitination from IRF3 K366, preventing autophagic degradation; TBK1 phosphorylation triggers AXIN1 phase separation that enhances IRF3 activation and type I IFN production, revealing a Wnt-independent immune signaling role.

    Evidence Co-IP, K48-specific ubiquitination assay, phase separation imaging, TBK1 phosphorylation assay, pharmacological validation

    PMID:39384753

    Open questions at the time
    • Whether AXIN1 phase separation also concentrates destruction complex components
    • In vivo antiviral phenotype of AXIN1 deficiency
  18. 2024 Medium

    Lactylation at K147 as a hypoxia-responsive degradation signal: hypoxia-induced lactylation of AXIN1 at K147 promotes its ubiquitination and degradation, enhancing glycolysis and stemness, revealing metabolic regulation of AXIN1 stability through a novel PTM at the same site regulated by acetylation.

    Evidence Mass spectrometry lactylation site mapping, K147 mutagenesis, ECAR/glycolysis assay, in vivo xenograft

    PMID:38972426

    Open questions at the time
    • Identity of the lactyl-transferase and the E3 ligase triggered by lactylation
    • Interplay between K147 lactylation, acetylation, and SIRT4 deacetylation under physiological conditions

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major unresolved questions include: the full-length structure of the AXIN1 complex with all partners, the mechanism by which Wnt inhibits β-catenin ubiquitination within the intact complex, how AXIN1 phase separation integrates Wnt and innate immune signaling, and the functional interplay of competing PTMs at K147.
  • No full-length structural model of the assembled destruction complex
  • Mechanism of Wnt-induced ubiquitination block within the intact complex remains undefined
  • In vivo validation of AXIN1 phase separation in Wnt and immune contexts

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
Localization
GO:0005829 cytosol 3 GO:0005886 plasma membrane 2 GO:0005634 nucleus 1
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-392499 Metabolism of proteins 5 R-HSA-1643685 Disease 4 R-HSA-5357801 Programmed Cell Death 2 R-HSA-168256 Immune System 1
Partners
APCCSNK1ECTNNB1GSK3BIRF3NRF2PCDHGC3YAP1
Complex memberships
c-Myc degradation complex (GSK3β/Pin1/PP2A-B56α)β-catenin destruction complex (APC/GSK3β/CK1/β-TrCP)

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 AXIN1 mutations in hepatocellular carcinomas lead to increased nuclear beta-catenin/TCF DNA binding, and adenovirus-mediated transfer of wild-type AXIN1 induces apoptosis in HCC and colorectal cancer cells with activated beta-catenin signaling, establishing AXIN1 as a tumor suppressor that negatively regulates the Wnt/beta-catenin pathway. Adenoviral gene transfer, TCF/beta-catenin DNA binding assay, mutation sequencing Nature genetics High 10700176
2001 A missense mutation in the GSK3-binding domain of zebrafish Axin1 (masterblind allele) abolishes Axin1 binding to Gsk3 and disrupts Tcf-dependent transcription, demonstrating that Axin1-GSK3 interaction is required for anterior neural patterning; overexpression of wild-type Axin1 or Gsk3beta rescues the phenotype. Genetic epistasis (zebrafish mutant), overexpression rescue, Tcf reporter assay Genes & development High 11390362
2009 Axin1 acts as a scaffold protein to promote formation of a c-Myc degradation complex containing GSK3beta, Pin1, and PP2A-B56alpha; Axin1 knockdown decreases association of c-Myc with these proteins, reduces T58 phosphorylation, enhances S62 phosphorylation, and increases c-Myc stability, while acute Axin1 expression reduces c-Myc levels and suppresses its transcriptional activity. Co-immunoprecipitation, siRNA knockdown, phosphorylation analysis, c-Myc stability assay The EMBO journal High 19131971
2012 Beta-catenin is phosphorylated, ubiquitinated, and degraded by the proteasome all within an intact Axin1 complex; Wnt signaling suppresses beta-catenin ubiquitination within the complex without causing complex disassembly or inhibiting phosphorylation, leading to complex saturation by phospho-beta-catenin and allowing newly synthesized free beta-catenin to accumulate. Quantitative mass spectrometry under endogenous conditions, immunoprecipitation, proteasome inhibitor assays in multiple cell types Cell High 22682247
2010 The central scaffolding region of Axin1 implicated in binding GSK3beta and beta-catenin is natively unfolded (intrinsically disordered), suggesting that this unfolded nature facilitates dynamic interactions that position the kinase GSK3beta to phosphorylate its substrate beta-catenin. Biochemical and biophysical characterization (NMR, CD spectroscopy, size-exclusion chromatography) Journal of molecular biology High 21087614
2011 Axin1 scaffold protein promotes Myc protein instability in breast cancer: decreased AXIN1 expression and altered splice variant ratio in breast cancer correlates with increased Myc stability, elevated S62 phosphorylation, and decreased T58 phosphorylation, establishing Axin1 as a coordinator of the Myc degradation complex. Splice variant analysis, protein stability assay, phospho-specific immunoblotting, breast cancer cell lines and primary tumors PNAS Medium 21808024
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 requiring the DIX domain and Ser614 of Axin1, and Axin1 prevents bacterial invasiveness and inflammatory response in intestinal epithelial cells. Loss-of-function (knockdown), domain mapping (DIX domain and Ser614 mutants), ubiquitination and SUMOylation assays PloS one Medium 22509369
2014 Axin1 physically associates with NRF2 (via the central region of Axin1 and Neh4/Neh5 domains of NRF2) in a WNT-3A-regulated complex; Axin1 knockdown increases NRF2 protein levels, Axin1 stabilization (tankyrase inhibition) blocks WNT/NRF2 signaling, and liver-specific conditional Axin1 knockout mice show upregulation of the NRF2 transcriptional signature, revealing a non-canonical WNT-Axin1-NRF2 axis regulating hepatic antioxidant metabolism. Co-immunoprecipitation, domain mapping, siRNA knockdown, tankyrase inhibition, conditional liver-specific KO mice Antioxidants & redox signaling High 25336178
2016 RUNX1 and estrogen receptor (ER) occupy adjacent elements in the AXIN1 second intron, and RUNX1 antagonizes oestrogen-mediated AXIN1 transcriptional suppression; loss of RUNX1 in ER+ mammary epithelial cells decreases AXIN1, increases beta-catenin, deregulates mitosis, and stimulates proliferation, effects rescued by AXIN1 stabilization. ChIP assay, RNA-seq, in vivo conditional KO, AXIN1 stabilization rescue experiments Nature communications High 26916619
2016 The gamma-Protocadherin-C3 (γ-Pcdh-C3) isoform physically interacts with Axin1 via its unique variable cytoplasmic domain (VCD); the C3 VCD competes with Dishevelled for binding to the DIX domain of Axin1, stabilizing Axin1 at the membrane, reducing phosphorylation of Wnt co-receptor Lrp6, and inhibiting canonical Wnt signaling. Co-immunoprecipitation, competition binding assay (VCD vs. Dvl for DIX domain), conditional transgenic in vivo Scientific reports High 27530555
2016 Axin-1 localizes around the meiotic spindle in mouse oocytes; siRNA-mediated knockdown of Axin1 causes defective spindles, misaligned chromosomes, failure of first polar body extrusion, impaired gamma-tubulin/Nek9 spindle pole localization, and retained BubR1 at kinetochores, establishing Axin1 as critical for spindle organization and meiotic cell cycle progression. Immunofluorescence localization, siRNA knockdown with defined phenotypic readout in mouse oocytes PloS one Medium 27284927
2016 Vitamin D receptor (VDR) is a transcriptional regulator of AXIN1: VDR binds a genomic regulatory region of the AXIN1 gene (ChIP-confirmed), and VDR deletion reduces cytosolic Axin1 protein and mRNA levels without a change in Axin1 nuclear fraction; Axin1 knockdown does not reciprocally affect VDR, establishing unidirectional transcriptional control. ChIP assay, conditional VDR KO mouse (VDRΔIEC), subcellular fractionation, RT-PCR and Western blot The Journal of steroid biochemistry and molecular biology High 27601169
2017 TRIM65 E3 ubiquitin ligase directly binds Axin1 and promotes its ubiquitination and proteasomal degradation, thereby activating beta-catenin signaling; TRIM65 overexpression reduces Axin1 protein and promotes HCC cell growth and metastasis, while knockdown has opposite effects. Co-immunoprecipitation, ubiquitination assay, overexpression/knockdown with functional readouts in vitro and in vivo Journal of cell science Medium 28754688
2018 C9orf140, identified by tandem-affinity purification/mass spectrometry as an Axin1-interacting protein, outcompetes PP2A for binding to Axin1, shifts the balance between phosphorylation and dephosphorylation of beta-catenin, and mediates a negative feedback loop of Wnt/beta-catenin signaling; C9orf140 is induced by Wnt/beta-catenin. Tandem-affinity purification/mass spectrometry, Co-IP, competition binding assay, zebrafish embryo epistasis Oncogene Medium 29531269
2018 Peptide microarray mapping of AXIN1 identified at least three binding epitopes in the central intrinsically disordered region (IDR) for each of CK1ε, c-Myc, Pin1, and p53; functionally validated AXIN1-CK1ε epitopes with peptide mimics and deletion variants; proposed model in which AXIN1 competes with Dishevelled for CK1ε binding to regulate CK1ε-induced DVL phosphorylation and Wnt/beta-catenin signaling. Peptide microarray, epitope-mimicking peptides, AXIN1 deletion variants, functional Wnt assay The Journal of biological chemistry Medium 30166345
2019 Axin1 deletion cooperates with c-Met to induce HCC in mice in a beta-catenin-dependent but Notch-independent manner; silencing beta-catenin in AXIN1-null HCC cells strongly inhibited proliferation, while blocking Notch via dominant-negative RBP-J or Notch2 ablation did not affect hepatocarcinogenesis, establishing the genetic epistasis of Axin1-loss-driven HCC. CRISPR/Cas9 Axin1 deletion, liver-specific Ctnnb1 KO epistasis, dominant-negative Notch2 ablation, mouse HCC model Hepatology High 30737831
2019 Axin1 forms a complex with AMPK in contracting skeletal muscle (reciprocal co-IP confirmed); contraction/exercise upregulates Axin1 protein in an AMPK-dependent manner, and siRNA knockdown of either AMPK or Axin1 blocks contraction-induced GTP loading of Rac1, PAK phosphorylation, and glucose uptake, placing Axin1 in an AMPK/Axin1-Rac1 signaling axis for contraction-stimulated muscle glucose uptake. Reciprocal co-immunoprecipitation, siRNA knockdown, Rac1-GTP loading assay, glucose uptake assay in C2C12 myotubes and mouse exercise model American journal of physiology. Endocrinology and metabolism Medium 31846370
2020 USP44 deubiquitinase directly interacts with Axin1, reduces its ubiquitination level (without affecting mRNA), stabilizes Axin1 protein, and thereby suppresses Wnt/beta-catenin signaling; Axin1 knockdown abolishes USP44-mediated effects on CRC cell proliferation and apoptosis. Co-immunoprecipitation, ubiquitination assay, mRNA vs. protein analysis, functional rescue with Axin1 KD Cell biology international Medium 32285989
2019 Axin-1 binds Caveolin-1 via its C-terminal region (710-797 aa) interacting with the N-terminal region (1-100 aa) of Caveolin-1; disrupting this interaction by CRISPR/Cas9 increases inflammatory cytokine production (TNF-α, IL-6) and reduces beta-catenin expression in LPS-challenged alveolar type I epithelial cells. Yeast two-hybrid, co-immunoprecipitation with domain mapping, CRISPR/Cas9 disruption of interaction, cytokine ELISA Biochemical and biophysical research communications Medium 30954225
2021 YTHDF2, an m6A reader, directly binds AXIN1 mRNA and promotes its decay, thereby activating Wnt/beta-catenin signaling; AXIN1 knockout rescues the inhibitory effects of YTHDF2 depletion on lung cancer cell proliferation, colony-formation, and migration. RNA-seq, m6A-seq, CLIP-seq, RIP-seq integration, mRNA decay assay, genetic rescue (AXIN1 KO) Cell death & disease High 33980824
2021 CircAXIN1 encodes a novel 295-aa protein (AXIN1-295aa) that competitively interacts with APC, disrupting the beta-catenin destruction complex and causing beta-catenin nuclear translocation and TCF-driven transcription; immunoprecipitation confirmed AXIN1-295aa/APC competitive interaction. FLAG-tagged overexpression, immunoblotting, mass spectrometry, luciferase reporter, immunoprecipitation competition assay, ChIP, in vitro and in vivo functional assays Molecular cancer Medium 34863211
2022 AXIN1 binds to YAP/TAZ in human HCC cells and regulates their stability; loss of AXIN1 strongly induces nuclear YAP/TAZ, and co-deletion of Yap and Taz significantly inhibits c-Met/sgAxin1-driven HCC development in mice, establishing YAP/TAZ as major effectors downstream of AXIN1-loss in hepatocarcinogenesis. Co-immunoprecipitation, conditional KO epistasis (Yap/Taz KO in Axin1-deleted liver tumors), TTR-CreERT2 KO during tumor progression Hepatology High 35921500
2022 SIRT4 translocates from mitochondria to the cytoplasm upon Wnt stimulation and deacetylates Axin1 at Lys147 (within the RGS domain); the Axin1-K147R mutant impairs assembly of beta-TrCP into the destruction complex, leading to beta-catenin accumulation even without Wnt stimulation, revealing acetylation as a regulatory PTM of Axin1 activity. SIRT4 translocation imaging, in vitro deacetylation assay, Axin1-K147R mutagenesis, beta-TrCP Co-IP, beta-catenin accumulation assay Frontiers in oncology Medium 35707358
2022 UCHL5 deubiquitinase physically interacts with multiple domains of Axin1 and is required for both stabilization and polymerization of Axin1 proteins; these effects are mediated through the DIX domain of Axin1 but do not require UCHL5 deubiquitinating enzymatic activity, identifying a non-catalytic mechanism by which UCHL5 potentiates Axin1 function in the beta-catenin destruction complex. Co-immunoprecipitation, Axin1 polymerization assay, catalytically-dead UCHL5 mutant, siRNA knockdown with Wnt reporter Scientific reports Medium 35256667
2023 γ-Pcdh-C3 interacts with Axin1 in the cortex in vivo; mice lacking γC3 exhibit disrupted Axin1 localization to synaptic fractions and severely decreased dendritic complexity of cortical pyramidal neurons; rescue experiments in γC3-KO neurons confirm γC3 promotes dendritic arborization through an Axin1-dependent mechanism mediated via its variable cytoplasmic domain. CRISPR/Cas9 KO mouse, subcellular fractionation, dendritic morphology analysis, cultured neuron rescue with domain mutants The Journal of neuroscience High 36604170
2024 Analysis of 80 tumor-associated AXIN1 missense variants in the GSK3beta, beta-catenin, and RGS/APC interaction domains identified 18 that significantly affect beta-catenin signaling; co-immunoprecipitation showed most lost binding to the partner corresponding to the mutated domain; truncating mutations inversely correlated with beta-catenin regulatory function by protein length. Systematic beta-catenin signaling reporter assay, co-immunoprecipitation of 80 variants, protein structure analysis Cancer research High 38359148
2024 AXIN1 maintains stability of IRF3 by preventing p62-mediated autophagic degradation: AXIN1 recruits USP35 to remove K48-linked ubiquitination at IRF3 K366. Upon virus infection, phosphorylated TBK1 triggers AXIN1 phase separation, leading to increased IRF3 phosphorylation and enhanced type I IFN production. Co-immunoprecipitation, ubiquitination assay (K48-specific), phase separation imaging, TBK1 phosphorylation assay, USP35 recruitment assay, small molecule (KYA1797K) functional validation Signal transduction and targeted therapy High 39384753
2024 Lactylation of Axin1 at K147 induced by hypoxia promotes ubiquitination and proteasomal degradation of Axin1, leading to enhanced glycolysis and cell stemness; Axin1 K147 mutant (non-lactylatable) resists degradation and inhibits glycolysis even under hypoxia, while wild-type Axin1 overexpression suppresses tumor growth in vivo. Mass spectrometry-identified lactylation site, K147 mutagenesis, ubiquitination assay, ECAR/glycolysis assay, in vivo tumor xenograft Biochemical pharmacology Medium 38972426
2012 Conditional disruption of Axin1 in adult mouse liver results in acute hepatocyte proliferation, activation of Wnt target genes (Axin2, c-Myc, cyclin D1) and G2/M transition genes, without nuclear beta-catenin accumulation or changes in liver zonation characteristic of APC loss, and development of HCC in 5 of 9 mice after 1 year. Conditional Cre/loxP Axin1 KO mouse, qRT-PCR, immunoprecipitation, histology Gastroenterology High 22960659
2010 MAP3K1 interacts with Axin1 as an endogenous binding partner identified by immunoprecipitation-coupled proteomics; the Axin1-MAP3K1 interaction is induced and modulated by Wnt stimulation; MAP3K1 E3 ubiquitin ligase activity (not kinase activity) is required for TCF/LEF-driven Wnt target gene expression. Immunoprecipitation-coupled proteomics (MS), siRNA depletion, ubiquitin ligase and kinase mutant functional analysis Biological chemistry Medium 20128690
2017 Hsp90α/β associates with the GSK3β/Axin1/phospho-β-catenin complex in MCF-7 breast cancer cells; selective Hsp90 inhibition disrupts this complex, confirming Hsp90 modulates beta-catenin phosphorylation by participating in the destruction complex. Immunoprecipitation, confocal microscopy, selective Hsp90 inhibition Biochemical and biophysical research communications Low 21925151
2018 TRIM11 E3 ubiquitin ligase interacts with Axin1 (Co-IP confirmed) and promotes Axin1 ubiquitination and degradation, thereby activating beta-catenin signaling to promote lymphoma cell proliferation. Co-immunoprecipitation, ubiquitination detection assay, TRIM11 KD/OE functional assays Experimental cell research Medium 31786079
2020 RBM47 RNA-binding protein binds AXIN1 mRNA and stabilizes it, thereby suppressing Wnt/beta-catenin signaling and inhibiting NSCLC cell proliferation, migration, and invasion. RIP (RNA immunoprecipitation), mRNA stability assay, lentiviral KD, in vivo xenograft Surgical oncology Medium 32891348

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 732 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 204 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 132 34863211
2014 AXIN1 and AXIN2 variants in gastrointestinal cancers. Cancer letters 115 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 91 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 72 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 63 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 56 28754688
2015 5-hydroxytryptamine receptor (5-HT1DR) promotes colorectal cancer metastasis by regulating Axin1/β-catenin/MMP-7 signaling pathway. Oncotarget 56 26214021
2017 Loss of AXIN1 drives acquired resistance to WNT pathway blockade in colorectal cancer cells carrying RSPO3 fusions. EMBO molecular medicine 55 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 45 32891348
2020 LncRNA NEAT1 Regulates the Development of Parkinson's Disease by Targeting AXIN1 Via Sponging miR-212-3p. Neurochemical research 42 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 40 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 38 32167488
2016 The γ-Protocadherin-C3 isoform inhibits canonical Wnt signalling by binding to and stabilizing Axin1 at the membrane. Scientific reports 38 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
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 30 35489084
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
2024 Hypoxia exposure induces lactylation of Axin1 protein to promote glycolysis of esophageal carcinoma cells. Biochemical pharmacology 29 38972426
2021 Evaluation of AXIN1 and AXIN2 as targets of tankyrase inhibition in hepatocellular carcinoma cell lines. Scientific reports 29 33811251
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 29 34495485
2024 The scaffold protein AXIN1: gene ontology, signal network, and physiological function. Cell communication and signaling : CCS 28 38291457
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 26 22509369
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
2019 An AMPK/Axin1-Rac1 signaling pathway mediates contraction-regulated glucose uptake in skeletal muscle cells. American journal of physiology. Endocrinology and metabolism 25 31846370
2011 Generation of Axin1 conditional mutant mice. Genesis (New York, N.Y. : 2000) 25 21344612
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 24 30070692
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
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
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 20 36604170
2022 Differential requirement of Hippo cascade during CTNNB1 or AXIN1 mutation-driven hepatocarcinogenesis. Hepatology (Baltimore, Md.) 20 35921500
2022 Axin1 Protects Colon Carcinogenesis by an Immune-Mediated Effect. Cellular and molecular gastroenterology and hepatology 20 36356835
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
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
2021 miR-3574 ameliorates intermittent hypoxia-induced cardiomyocyte injury through inhibiting Axin1. Aging 16 33582657
2022 The E3 Ubiquitin Ligase TRIM11 Facilitates Gastric Cancer Progression by Activating the Wnt/β-Catenin Pathway via Destabilizing Axin1 Protein. Journal of oncology 15 35237324
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 AXIN1 boosts antiviral response through IRF3 stabilization and induced phase separation. Signal transduction and targeted therapy 13 39384753
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
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
2024 UBE2N promotes cell viability and glycolysis by promoting Axin1 ubiquitination in prostate cancer cells. Biology direct 12 38715121
2023 TRIM37 promotes gallbladder cancer proliferation by activating the Wnt/β-catenin pathway via ubiquitination of Axin1. Translational oncology 12 37379772
2021 AXIN1 knockout does not alter AMPK/mTORC1 regulation and glucose metabolism in mouse skeletal muscle. The Journal of physiology 12 33913171
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
2021 Targeting TRIM54/Axin1/β-Catenin Axis Prohibits Proliferation and Metastasis in Hepatocellular Carcinoma. Frontiers in oncology 11 34956880
2020 Axin1 inhibits proliferation, invasion, migration and EMT of hepatocellular carcinoma by targeting miR-650. American journal of translational research 11 32269738
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
2022 UCHL5 controls β-catenin destruction complex function through Axin1 regulation. Scientific reports 10 35256667
2022 Axin1: A novel scaffold protein joins the antiviral network of interferon. Molecular microbiology 10 36308071
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
2019 Insertion of a chimeric retrotransposon sequence in mouse Axin1 locus causes metastable kinky tail phenotype. Mobile DNA 10 31073336
2016 AXIN1 Expression and Localization in Meningiomas and Association to Changes of APC and E-cadherin. Anticancer research 10 27630299