ArticleOpen biology2015
Disinhibition of the HECT E3 ubiquitin ligase WWP2 by polymerized Dishevelled.
Article in Open biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 45 citations in OpenAlex.
- HECT-type ubiquitin ligases: Emerging principles in the era of full-length structures.The Journal of biological chemistry · 2026Review
- NEDD4 family E3 ligases in osteoporosis: mechanisms and emerging potential therapeutic targets.Journal of orthopaedic surgery and research · 2025Review
- Emerging regulatory mechanisms and functions of biomolecular condensates: implications for therapeutic targets.Signal transduction and targeted therapy · 2025Review
- Carboxy-terminal polyglutamylation regulates signaling and phase separation of the Dishevelled protein.The EMBO journal · 2024Article
- Alternative mechanisms of Notch activation by partitioning into distinct endosomal domains.The Journal of cell biology · 2024Article
- Spatial Mechano-Signaling Regulation of GTPases through Non-Degradative Ubiquitination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Divergent regulation of α-arrestin ARRDC3 function by ubiquitination.Molecular biology of the cell · 2023Article
- E3 Ubiquitin Ligase Regulators of Notch Receptor Endocytosis: From Flies to Humans.Biomolecules · 2022Review
- Article
- Regulation of Dishevelled DEP domain swapping by conserved phosphorylation sites.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Adaptors as the regulators of HECT ubiquitin ligases.Cell death and differentiation · 2021Review
- Article
- The Tumour Suppressor TMEM127 Is a Nedd4-Family E3 Ligase Adaptor Required by Salmonella SteD to Ubiquitinate and Degrade MHC Class II Molecules.Cell host & microbe · 2020Article
- Activity of Smurf2 Ubiquitin Ligase Is Regulated by the Wnt Pathway Protein Dishevelled.Cells · 2020Article
- YTHDF2 promotes mitotic entry and is regulated by cell cycle mediators.PLoS biology · 2020Article
- Acetylation of conserved DVL-1 lysines regulates its nuclear translocation and binding to gene promoters in triple-negative breast cancer.Scientific reports · 2019Article
- Review
- USP9X Deubiquitylates DVL2 to Regulate WNT Pathway Specification.Cell reports · 2019Article
- WWP2 Is One Promising Novel Oncogene.Pathology oncology research : POR · 2019Review
- WW domain-mediated regulation and activation of E3 ubiquitin ligase Suppressor of Deltex.The Journal of biological chemistry · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
Dishevelled is a pivot in Wnt signal transduction, controlling both β-catenin-dependent transcription to specify proliferative cell fates, and cell polarity and other non-nuclear events in post-mitotic cells. In response to Wnt signals, or when present at high levels, Dishevelled forms signalosomes by dynamic polymerization. Its levels are controlled by ubiquitylation, mediated by various ubiquitin ligases, including NEDD4 family members that bind to a conserved PPxY motif in Dishevelled (mammalian Dvl1-3). Here, we show that Dvl2 binds to the ubiquitin ligase WWP2 and unlocks its ligase activity from autoinhibition. This disinhibition of WWP2 depends on several features of Dvl2 including its PPxY motif and to a lesser extent its DEP domain, but crucially on the ability of Dvl2 to polymerize, indicating that WWP2 is activated in Wnt signalosomes. We show that Notch intracellular domains are substrates for Dvl-activated WWP2 and their transcriptional activity is consequently reduced, providing a molecular mechanism for cross-talk between Wnt and Notch signalling. These regulatory interactions are conserved in Drosophila whose WWP2 orthologue, Suppressor-of-deltex, downregulates Notch signalling upon activation by Dishevelled in developing wing tissue. Attentuation of Notch signalling by Dishevelled signalosomes could be important during the transition of cells from the proliferative to the post-mitotic state.
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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.