ArticleNature communications2023
The USP46 complex deubiquitylates LRP6 to promote Wnt/β-catenin signaling.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- Supplemental exposure to polystyrene nanoplastics synergistically amplifies calcium oxalate crystal-induced injury to renal tubular epithelium, accelerating the formation of calcium oxalate kidney stones.Particle and fibre toxicology · 2026Article
- PLK1 stabilizes β-catenin to drive colorectal carcinogenesis through NFKB2-mediated transcriptional activation of USP2a and site-specific phosphorylation.Theranostics · 2026Article
- Nuclear β-catenin: molecular regulation, challenges and therapeutic opportunities.Cell communication and signaling : CCS · 2025Review
- CRISPR/Cas9-Mediated Disruption ofInternational journal of molecular sciences · 2025Article
- Cannabidiol restores hematopoietic stem cell stemness in mouse through Atf2-Lrp6 axis after acute irradiation.MedComm · 2025Article
- Wnt signalosomes: What we know that we do not know.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- The mechanosensitive protein ANTXR1 is involved in maintaining cartilage homeostasis in post-traumatic osteoarthritis.Frontiers in cell and developmental biology · 2025Article
- Review
- The initial implementation of the transverse bone transport technique in the post-radiation region of the mandible. A pre-clinical in vivo study.BMC oral health · 2024Article
- WDR20 prevents hepatocellular carcinoma senescence by orchestrating the simultaneous USP12/46-mediated deubiquitination of c-Myc.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The role of ubiquitination in health and disease.MedComm · 2024Review
- Wnt/β-catenin signaling in the development and therapeutic resistance of non-small cell lung cancer.Journal of translational medicine · 2024Review
- 1-L Transcription of SARS-CoV-2 Spike Protein S1 Subunit.International journal of molecular sciences · 2024Article
- WNT/β-catenin regulatory roles on PD-(L)1 and immunotherapy responses.Clinical and experimental medicine · 2024Review
- The USP46 deubiquitylase complex increases Wingless/Wnt signaling strength by stabilizing Arrow/LRP6.Nature communications · 2023Article
Corrections and comments
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Authors and funding
26 authors at 8 institutions in 2 countries.
Funding
Abstract
The relative abundance of Wnt receptors plays a crucial role in controlling Wnt signaling in tissue homeostasis and human disease. While the ubiquitin ligases that ubiquitylate Wnt receptors are well-characterized, the deubiquitylase that reverses these reactions remains unclear. Herein, we identify USP46, UAF1, and WDR20 (USP46 complex) as positive regulators of Wnt signaling in cultured human cells. We find that the USP46 complex is similarly required for Wnt signaling in Xenopus and zebrafish embryos. We demonstrate that Wnt signaling promotes the association between the USP46 complex and cell surface Wnt coreceptor, LRP6. Knockdown of USP46 decreases steady-state levels of LRP6 and increases the level of ubiquitylated LRP6. In contrast, overexpression of the USP46 complex blocks ubiquitylation of LRP6 by the ubiquitin ligases RNF43 and ZNFR3. Size exclusion chromatography studies suggest that the size of the USP46 cytoplasmic complex increases upon Wnt stimulation. Finally, we show that USP46 is essential for Wnt-dependent intestinal organoid viability, likely via its role in LRP6 receptor homeostasis. We propose a model in which the USP46 complex increases the steady-state level of cell surface LRP6 and facilitates the assembly of LRP6 into signalosomes via a pruning mechanism that removes sterically hindering ubiquitin chains.
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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.