Critical Scaffolding Regions of the Tumor Suppressor Axin1 Are Natively Unfolded
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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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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.”
From Intrinsically disordered proteins play diverse roles in cell signaling (2022) · cites this paper as [263]
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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.
- ORCID
- 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
- bronze
- doi.org
- Licence
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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