Cited by 58Wnt/β-catenin signaling in development and cancerProtein Structure and DynamicsSignaling Pathways in Disease

Critical Scaffolding Regions of the Tumor Suppressor Axin1 Are Natively Unfolded

Open access
Noutsou, Maria, Duarte, Afonso M.S., Anvarian, Zeinab, Didenko, Tatiana, Minde, David P., Kuper, Ineke, de Ridder, Isabel, Oikonomou, Christina +4 more·2011·Journal of Molecular Biology

Abstract

The Wnt pathway tumor-suppressor protein Axin coordinates the formation of a critical multiprotein destruction complex that serves to downregulate β-catenin protein levels, thereby preventing target gene activation. Given the lack of structural information on some of the major functional parts of Axin, it remains unresolved how the recruitment and positioning of Wnt pathway kinases, such as glycogen synthase kinase 3β, are coordinated to bring about β-catenin phosphorylation. Using various biochemical and biophysical methods, we demonstrate here that the central region of Axin that is implicated in binding glycogen synthase kinase 3β and β-catenin is natively unfolded. Our results support a model in which the unfolded nature of these critical scaffolding regions in Axin facilitates dynamic interactions with a kinase and its substrate, which in turn act upon each other.

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Crossref · 10.1016/j.jmb.2010.11.013

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  • Addition of this disordered axin segment to solutions of β-catenin and GSK3b greatly accelerates the rate of phosphorylation of β-catenin by GSK3b.

    “Furthermore, addition of this disordered segment to solutions of β-catenin and GSK3b greatly accelerates the rate of phosphorylation of β-catenin by GSK3b.”

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Authors
Noutsou, M., Duarte, A. M. S., Anvarian, Z., Didenko, T., Minde, D. P., Kuper, I., de Ridder, I., Oikonomou, C., Friedler, A., Boelens, R., Rüdiger, S. G. D., & Maurice, M. M.
Affiliations
  • University Medical Center Utrecht (NL)
  • Utrecht University (NL)
  • Hebrew University of Jerusalem (IL)
Corresponding author
  • Rüdiger, Stefan G.D.
  • Maurice, Madelon M.
Venue
Journal of Molecular Biology
Publisher
Elsevier BV
Published
2011-01
Volume
405
Issue
3
Pages
773-786
ISSN
0022-2836 (ISSN-L)
OpenAlex
W2020317656
Cited by
58
References
69
Citations by year
2025: 2 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 4 · 2019: 2 · 2018: 4 · 2017: 5 · 2016: 5 · 2015: 3 · 2014: 6 · 2013: 4 · 2012: 11
FWCI
2.34
Type
journal article
Language
en
Open access
Locations
  • Journal of Molecular Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • Leiden Repository (Leiden University) (submittedVersion)
  • Utrecht University Repository (Utrecht University) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
  • Figshare (cc-by)
Funders
  • Dutch Cancer Society (UU 2006-3508, 242958, 203413)
  • European Research Council
  • European Research Council starting
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Keywords
AXIN1, intrinsically disordered proteins, Wnt signaling, glycogen synthase kinase-3β, β-catenin, protein-protein interaction, protein structure, kinase-substrate interactions
MeSH terms
Glycogen Synthase Kinase 3 beta, Binding Sites, Humans, Models, Molecular, Protein Binding, Repressor Proteins, Tumor Suppressor Proteins, Glycogen Synthase Kinase 3, Matrix Attachment Regions, Adaptor Proteins, Signal Transducing, Wnt Proteins, beta Catenin, Protein Unfolding, Axin Protein

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