ArticleMolecular cell2016
Wnt Signalosome Assembly by DEP Domain Swapping of Dishevelled.
Article in Molecular cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers.
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Who cites it
114 citing papers in PubMed, 184 citations in OpenAlex.
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- Phosphatase Activities of a Highly Stable High-Molecular-Mass Multiprotein Complex Isolated from Different Organs of the Sea CucumberInternational journal of molecular sciences · 2026Article
- Convergent mechanisms in Wnt and Hedgehog signaling.Science signaling · 2026Review
- Targeting frizzled receptors (FZDs) for anti-tumor therapy: From orthosteric to allosteric inhibition.Acta pharmaceutica Sinica. B · 2026Review
- Dishevelled PDZ domain targeting peptides modulate non-canonical Wnt5a/Ror signaling.Biochemistry and biophysics reports · 2026Article
- The E3 ubiquitin ligase Itch plays an essential role in kidney fibrosis by inhibiting Dvl2/GSK3β/β-catenin signaling pathway.Cell death and differentiation · 2026Article
- A Wnt-induced conformational phospho-switch in DVL3 controls association with Frizzled receptors and Wnt/β-catenin signaling.Science advances · 2026Article
- Antibody-Drug Conjugates Targeting Resistance-Associated Signaling Pathways: Recent Advances and Future Perspectives.International journal of molecular sciences · 2026Review
- Human papillomavirus16 E7 enhances cell stemness by regulating the APC2/SPIN4/β-catenin axis in cervical cancer.Oncogenesis · 2026Article
- Isoleucine and valine regulate the BCAA antagonism by influencing insulin function in broiler chickens.Journal of animal science and biotechnology · 2026Article
- Topography-driven movement of biomolecular condensates.PloS one · 2026Article
- Computational Identification of Potential Shape-Shifting Proteins from Structures.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Targeting β-catenin: PROTACs and precision degraders for Wnt-driven cancers.Frontiers in oncology · 2026Review
- Smurf1 promotes gastric cancer progression by regulating Axin2-dependent Wnt signaling pathway.Scientific reports · 2025Article
- The LINC01612-DVL2-WNT axis promotes human endoderm differentiation.Stem cell reports · 2025Article
- A Unique Trimeric Assembly of Human Dishevelled 1 PDZ Domain in Crystal: Implication of Homo- and Hetero-Oligomerization During Wnt Signaling Process.Molecules (Basel, Switzerland) · 2025Article
- The Significance of the Wnt/β-Catenin Pathway and Related Proteins in Gastrointestinal Malignancies.International journal of molecular sciences · 2025Review
- Dishevelled localization and function are differentially regulated by structurally distinct sterols.iScience · 2025Article
- WNT-induced association of Frizzled and LRP6 is not sufficient for the initiation of WNT/β-catenin signaling.Nature communications · 2025Article
- Wnt signalosome assembly is governed by conformational flexibility of Axin and by the AP2 clathrin adaptor.Nature communications · 2025Article
54 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Extracellular signals are often transduced by dynamic signaling complexes ("signalosomes") assembled by oligomerizing hub proteins following their recruitment to signal-activated transmembrane receptors. A paradigm is the Wnt signalosome, which is assembled by Dishevelled via reversible head-to-tail polymerization by its DIX domain. Its activity causes stabilization of β-catenin, a Wnt effector with pivotal roles in animal development and cancer. How Wnt triggers signalosome assembly is unknown. Here, we use structural analysis, as well as biophysical and cell-based assays, to show that the DEP domain of Dishevelled undergoes a conformational switch, from monomeric to swapped dimer, to trigger DIX-dependent polymerization and signaling to β-catenin. This occurs in two steps: binding of monomeric DEP to Frizzled followed by DEP domain swapping triggered by its high local concentration upon Wnt-induced recruitment into clathrin-coated pits. DEP domain swapping confers directional bias on signaling, and the dimerization provides cross-linking between Dishevelled polymers, illustrating a key principle underlying signalosome formation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.