Inhibition of Wnt Signaling Pathway by a Novel Axin-binding Protein*

Axin forms a complex with adenomatous polyposis coli gene product, glycogen synthase kinase-3β (GSK-3β), β-catenin, Dvl, and protein phosphatase 2A and functions as a scaffold protein in the Wnt signaling pathway. In the Axin complex, GSK-3β efficiently phosphorylates β-catenin, which is then ubiquitinated and degraded by proteasome. We isolated a novel protein that binds to Axin and named it Axam (for Axinassociating molecule). Axam formed a complex with Axin in intact cells and bound directly to Axin. Axam inhibited the complex formation of Dvl with Axin and the activity of Dvl to suppress GSK-3β-dependent phosphorylation of Axin. Furthermore, Axam induced the degradation of β-catenin in SW480 cells and inhibited Wnt-dependent axis duplication inXenopus embryos. These results suggest that Axam regulates the Wnt signaling pathway negatively by inhibiting the binding of Dvl to Axin.

• Publication year

  2000

• Venue

  Journal of Biological Chemistry

• Publication date

  2000-11-24

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1074/jbc.M005984200PMID 10944533
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Regulation of the protein kinase activity of ShaggyZeste-white3 by components of the Wingless pathway in Drosophila cells and embryos.

  2016cited by this paper
• Molecular Cloning: A Laboratory Manual

  2001cited by this paper
• Wnt signaling in oncogenesis and embryogenesis--a look outside the nucleus.

  2000cited by this paper
• Interaction of Dishevelled and XenopusAxin-Related Protein Is Required for Wnt Signal Transduction

  2000cited by this paper
• Protein Phosphatase 2Cα Dephosphorylates Axin and Activates LEF-1-dependent Transcription*

  2000cited by this paper
• GSK-3β-dependent phosphorylation of adenomatous polyposis coli gene product can be modulated by β-catenin and protein phosphatase 2A complexed with Axin

  2000cited by this paper
• A GSK3β Phosphorylation Site in Axin Modulates Interaction with β-Catenin and Tcf-Mediated Gene Expression

  1999cited by this paper
• DIX Domains of Dvl and Axin Are Necessary for Protein Interactions and Their Ability To Regulate β-Catenin Stability

  1999cited by this paper
• Dishevelled Proteins Lead to Two Signaling Pathways

  1999cited by this paper
• Regulation of β-Catenin Signaling by the B56 Subunit of Protein Phosphatase 2A

  1999cited by this paper
• The F-box protein β-TrCP associates with phosphorylated β-catenin and regulates its activity in the cell

  1999cited by this paper
• Interaction of Axin and Dvl‐2 proteins regulates Dvl‐2‐stimulated TCF‐dependent transcription

  1999cited by this paper
• The SCFβ-TRCP–ubiquitin ligase complex associates specifically with phosphorylated destruction motifs in IκBα and β-catenin and stimulates IκBα ubiquitination in vitro

  1999cited by this paper
• Mechanism and function of signal transduction by the Wnt/β-catenin and Wnt/Ca2+ pathways

  1999cited by this paper
• The SCFbeta-TRCP-ubiquitin ligase complex associates specifically with phosphorylated destruction motifs in IkappaBalpha and beta-catenin and stimulates IkappaBalpha ubiquitination in vitro.

  1999cited by this paper
• The F-box protein beta-TrCP associates with phosphorylated beta-catenin and regulates its activity in the cell.

  1999cited by this paper
• Roles of Axin in the Wnt signalling pathway.

  1999cited by this paper
• Domains of Axin Involved in Protein–Protein Interactions, Wnt Pathway Inhibition, and Intracellular Localization

  1999cited by this paper
• Casein kinase I transduces Wnt signals

  1999cited by this paper
• Regulation of beta-catenin signaling by the B56 subunit of protein phosphatase 2A.

  1999cited by this paper
• Wnt-induced dephosphorylation of axin releases beta-catenin from the axin complex.

  1999cited by this paper
• Phosphorylation of Axin, a Wnt Signal Negative Regulator, by Glycogen Synthase Kinase-3β Regulates Its Stability*

  1999cited by this paper
• Identification of a Domain of Axin That Binds to the Serine/Threonine Protein Phosphatase 2A and a Self-binding Domain*

  1999cited by this paper
• Axin Directly Interacts with Plakoglobin and Regulates Its Stability*

  1999cited by this paper
• Distinct Domains of Mouse Dishevelled Are Responsible for the c-Jun N-terminal Kinase/Stress-activated Protein Kinase Activation and the Axis Formation in Vertebrates*

  1999cited by this paper
• Axin Forms a Complex with MEKK1 and Activates c-Jun NH2-terminal Kinase/Stress-activated Protein Kinase through Domains Distinct from Wnt Signaling*

  1999cited by this paper
• Regulation of the Protein Kinase Activity of ShaggyZeste-white3 by Components of the Wingless Pathway in Drosophila Cells and Embryos*

  1999cited by this paper
• An F‐box protein, FWD1, mediates ubiquitin‐dependent proteolysis of β‐catenin

  1999cited by this paper
• A GSK3beta phosphorylation site in axin modulates interaction with beta-catenin and Tcf-mediated gene expression.

  1999cited by this paper
• Axis determination in Xenopus involves biochemical interactions of axin, glycogen synthase kinase 3 and beta-catenin.

  1998cited by this paper
• Functional interaction of an axin homolog, conductin, with beta-catenin, APC, and GSK3beta.

  1998cited by this paper
• Downregulation of β-catenin by human Axin and its association with the APC tumor suppressor, β-catenin and GSK3β

  1998cited by this paper
• Downregulation of beta-catenin by human Axin and its association with the APC tumor suppressor, beta-catenin and GSK3 beta.

  1998cited by this paper
• Bridging of beta-catenin and glycogen synthase kinase-3beta by axin and inhibition of beta-catenin-mediated transcription.

  1998cited by this paper
• Mechanisms of Wnt signaling in development.

  1998cited by this paper
• Axis determination in Xenopus involves biochemical interactions of axin, glycogen synthase kinase 3 and β-catenin

  1998cited by this paper
• Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3beta and beta-catenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin.

  1998cited by this paper
• Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK‐3β and β‐catenin and promotes GSK‐3β‐dependent phosphorylation of β‐catenin

  1998cited by this paper
• Dishevelled activates JNK and discriminates between JNK pathways in planar polarity and wingless signaling.

  1998cited by this paper
• Axil, a member of the Axin family, interacts with both glycogen synthase kinase 3beta and beta-catenin and inhibits axis formation of Xenopus embryos.

  1998cited by this paper
• Axin, a Negative Regulator of the Wnt Signaling Pathway, Directly Interacts with Adenomatous Polyposis Coli and Regulates the Stabilization of β-Catenin*

  1998cited by this paper
• Bridging of β-catenin and glycogen synthase kinase-3β by Axin and inhibition of β-catenin-mediated transcription

  1998cited by this paper
• Signal transduction by the Wnt family of ligands.

  1998cited by this paper
• From cortical rotation to organizer gene expression: toward a molecular explanation of axis specification in Xenopus

  1998cited by this paper
• Axil, a Member of the Axin Family, Interacts with Both Glycogen Synthase Kinase 3β and β-Catenin and Inhibits Axis Formation ofXenopus Embryos

  1998cited by this paper
• Accumulation of Armadillo Induced by Wingless, Dishevelled, and Dominant-negative Zeste-white 3 Leads to Elevated DE-cadherin inDrosophila Clone 8 Wing Disc Cells*

  1997cited by this paper
• Wnt signaling: a common theme in animal development.

  1997cited by this paper
• Overexpression of the mouse dishevelled‐1 protein inhibits GSK‐3β‐mediated phosphorylation of tau in transfected mammalian cells

  1997cited by this paper
• The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation.

  1997cited by this paper
• Casein kinase 2 associates with and phosphorylates Dishevelled

  1997cited by this paper
• The axis-inducing activity, stability, and subcellular distribution of beta-catenin is regulated in Xenopus embryos by glycogen synthase kinase 3.

  1996cited by this paper
• Analysis of Dishevelled signalling pathways during Xenopus development.

  1996cited by this paper
• Binding of GSK3β to the APC-β-Catenin Complex and Regulation of Complex Assembly

  1996cited by this paper
• PEST sequences and regulation by proteolysis.

  1996cited by this paper
• Wingless inactivates glycogen synthase kinase‐3 via an intracellular signalling pathway which involves a protein kinase C.

  1996cited by this paper
• Binding of GSK3beta to the APC-beta-catenin complex and regulation of complex assembly.

  1996cited by this paper
• Phenotypic and molecular analysis of a transgenic insertional allele of the mouse Fused locus.

  1995cited by this paper
• The entire mesodermal mantle behaves as Spemann's organizer in dorsoanterior enhanced Xenopus laevis embryos.

  1988cited by this paper
• An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs.

  1987cited by this paper
• Functional messenger RNAs are produced by SP6 in vitro transcription of cloned cDNAs.

  1984cited by this paper
• A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.

  1976cited by this paper
• The effects of a lethal mutation responsible for duplications and twinning in mouse embryos.

  1949cited by this paper

• The scaffold protein AXIN1: gene ontology, signal network, and physiological function

  2024cites this paper
• GSK-3: An “Ace” Among Kinases

  2024cites this paper
• Deactivation of the beta-catenin transactivating complex

  2022cites this paper
• Loss of SUMO-specific protease 2 causes isolated glucocorticoid deficiency by blocking zonal transdifferentiation

  2022cites this paper
• Loss of SUMO-specific protease 2 causes isolated glucocorticoid deficiency by blocking adrenal cortex zonal transdifferentiation in mice

  2022cites this paper
• Regulation of SUMOylation Targets Associated With Wnt/β-Catenin Pathway

  2022influential citation
• The dopamine receptor antagonist trifluoperazine prevents phenotype conversion and improves survival in mouse models of glioblastoma

  2020cites this paper
• Advances of Wnt signalling pathway in dental development and potential clinical application

  2019cites this paper
• Axin Family of Scaffolding Proteins in Development: Lessons from C. elegans

  2019cites this paper
• The Dopamine Receptor Antagonist TFP Prevents Phenotype Conversion and Improves Survival in Mouse Models of Glioblastoma

  2019cites this paper
• Lithium Inhibits GSK3β and Augments GluN2A Receptor Expression in the Prefrontal Cortex

  2018cites this paper
• Integrating regulatory mechanisms of Wnt signaling in development and tissue homeostasis

  2017cites this paper
• The γ-Protocadherin-C3 isoform inhibits canonical Wnt signalling by binding to and stabilizing Axin1 at the membrane

  2016cites this paper
• Wnt signaling in regulation of biological functions of the nurse cell harboring Trichinella spp.

  2016cites this paper
• Short report Open Access

  2015cites this paper
• The SUMO proteases SENP1 and SENP2 play a critical role in nucleoporin homeostasis and nuclear pore complex function

  2014cites this paper
• CANONICAL WNT SIGNALING IN PANCREATIC DUCTAL ADENOMACARCINOMA

  2014cites this paper
• Regulation of Wnt/β-catenin signaling by posttranslational modifications

  2014cites this paper
• Gene Expression Profiling Identifies Microphthalmia-Associated Transcription Factor (MITF) and Dickkopf-1 (DKK1) as Regulators of Microenvironment-Driven Alterations in Melanoma Phenotype

  2014cites this paper
• Possible Role of Proto-Oncogenes in Colorectal Cancer — A Population Based Study

  2014cites this paper
• Different Roles for the Axin Interactions with the SAMP versus the Second Twenty Amino Acid Repeat of Adenomatous Polyposis Coli

  2014cites this paper
• Destabilization of Heterologous Proteins Mediated by the GSK3β Phosphorylation Domain of the β-Catenin Protein

  2013cites this paper
• Wnt/beta-Catenin Signaling and Small Molecule Inhibitors

  2012cites this paper
• Etude du rôle du gène suppresseur de tumeur WWOX et de ses partenaires dans la voie de signalisation Wnt/β-caténine et dans la carcinogenèse mammaire

  2012cites this paper
• Diversity of axin in signaling pathways and its relation to colorectal cancer

  2011cites this paper
• Control of Adipogenesis by the SUMO-Specific Protease SENP2

  2010cites this paper
• Inhibition of the Wnt/β-catenin pathway by the WWOX tumor suppressor protein

  2009cites this paper
• Wnt signaling and cancer development: therapeutic implication.

  2008cites this paper
• SUMO-Specific Protease 2 Is Essential for Modulating p53-Mdm2 in Development of Trophoblast Stem Cell Niches and Lineages

  2008cites this paper
• SUMOylation of HMGA2: selective destabilization of promyelocytic leukemia protein via proteasome

  2008cites this paper
• Modification in reverse: the SUMO proteases.

  2007cites this paper
• CANCER DRUG DISCOVERY AND DEVELOPMENT

  2007influential citation
• Microarray Analysis of the Cellular Pathways Involved in the Adaptation to and Progression of Motor Neuron Injury in the SOD1 G93A Mouse Model of Familial ALS

  2007cites this paper
• SUMO-1 Modification of PIASy, an E3 Ligase, Is Necessary for PIASy-Dependent Activation of Tcf-4

  2005influential citation
• Axin: A Master Scaffold for Multiple Signaling Pathways

  2004cites this paper
• Immunohistochemical analysis and mutational analyses of beta-catenin, Axin family and APC genes in hepatocellular carcinomas.

  2004cites this paper
• XSENP1, a novel sumo‐specific protease in Xenopus, inhibits normal head formation by down‐regulation of Wnt/β‐catenin signalling

  2004cites this paper
• Inhibition of the Canonical Wnt Signaling Pathway in Cytoplasm: a Novel Property of the Carboxyl Terminal Domains of Two Xenopus ELL Genes

  2004cites this paper
• Wnt/beta-catenin signaling pathway as a novel cancer drug target.

  2004cites this paper
• Negative regulation of Smad2 by PIASy is required for proper Xenopus mesoderm formation

  2004cites this paper
• XIdax, an inhibitor of the canonical Wnt pathway, is required for anterior neural structure formation in Xenopus

  2004cites this paper
• Sumoylation is involved in beta-catenin-dependent activation of Tcf-4.

  2003cites this paper
• Casein kinase I epsilon enhances the binding of Dvl-1 to Frat-1 and is essential for Wnt-3a-induced accumulation of beta-catenin.

  2003cites this paper
• Axin Utilizes Distinct Regions for Competitive MEKK1 and MEKK4 Binding and JNK Activation*

  2003cites this paper
• Identification and characterization of a novel Dvl‐binding protein that suppresses Wnt signalling pathway

  2003cites this paper
• Casein Kinase Iε Enhances the Binding of Dvl-1 to Frat-1 and Is Essential for Wnt-3a-induced Accumulation of β-Catenin*

  2003cites this paper
• Sumoylation is involved in β‐catenin‐dependent activation of Tcf‐4

  2003cites this paper
• Association of the Human SUMO-1 Protease SENP2 with the Nuclear Pore*

  2002cites this paper
• Nuclear Localization of Duplin, a β-Catenin-binding Protein, Is Essential for Its Inhibitory Activity on the Wnt Signaling Pathway*

  2002cites this paper
• Role of Wnt pathway in medulloblastoma oncogenesis

  2002cites this paper
• Versatile protein tag, SUMO: Its enzymology and biological function

  2002cites this paper
• Casein Kinase I and Casein Kinase II Differentially Regulate Axin Function in Wnt and JNK Pathways*

  2002cites this paper
• Desumoylation Activity of Axam, a Novel Axin-Binding Protein, Is Involved in Downregulation of β-Catenin

  2002cites this paper
• Piecing together the cancer puzzle.

  2002cites this paper
• SUMO-1 Modification of the C-terminal KVEKVD of Axin Is Required for JNK Activation but Has No Effect on Wnt Signaling*

  2002cites this paper
• Enzymes of the SUMO Modification Pathway Localize to Filaments of the Nuclear Pore Complex

  2002cites this paper
• SUMO-1 protease-1 regulates gene transcription through PML.

  2002cites this paper
• Activation of AXIN2 expression by beta-catenin-T cell factor. A feedback repressor pathway regulating Wnt signaling.

  2002cites this paper
• Regulation of neuritogenesis in neuroblastoma cells by components of the WNT signalling pathway.

  2002cites this paper
• SHOR TREPORT ROL EO FWN TPATHWA YI NMEDULLOBLASTOM AONCOGENESIS

  2002cites this paper
• Nuclear β-Catenin Signaling as a Target for Anticancer Drug Development

  2002cites this paper
• Synergistic Activation of the Wnt Signaling Pathway by Dvl and Casein Kinase Iε*

  2001cites this paper
• The multifaceted roles of glycogen synthase kinase 3beta in cellular signaling.

  2001cites this paper
• Inhibition of the Wnt Signaling Pathway by Idax, a Novel Dvl-Binding Protein

  2001cites this paper
• Synergistic activation of the Wnt signaling pathway by Dvl and casein kinase Iepsilon.

  2001cites this paper
• Physiological regulation of β-catenin stability by Tcf3 and CK1ε

  2001cites this paper
• Characterization of a Novel Mammalian SUMO-1/Smt3-specific Isopeptidase, a Homologue of Rat Axam, Which Is an Axin-binding Protein Promoting β-Catenin Degradation*

  2001cites this paper
• Inhibition of the Wnt Signaling Pathway by the PR61 Subunit of Protein Phosphatase 2A*

  2001cites this paper