ArticleCell communication and signaling : CCS2020
Protease associated domain of RNF43 is not necessary for the suppression of Wnt/β-catenin signaling in human cells.
Article in Cell communication and signaling : CCS, 2020. 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, 27 citations in OpenAlex.
- RING finger E3 ubiquitin ligases: novel therapeutic opportunities in melanoma.Cellular & molecular biology letters · 2026Review
- Loss of ZNRF3/RNF43 unleashes EGFR in cancer.eLife · 2026Article
- PRICKLE3 protects VANGL proteins from CK1-mediated phosphorylation and RNF43-mediated degradation.Communications biology · 2025Article
- WNK kinase regulates plasma membrane levels of the WNT inhibitor RNF43: A WNK-RNF43 circuit regulates WNT signal suppression.bioRxiv : the preprint server for biology · 2025Article
- ZNRF3 in neurodevelopmental disorders: insights into Wnt signaling and therapeutic potential.Neurogenetics · 2025Review
- Mechanistic insights into Wnt-β-catenin pathway activation and signal transduction.Nature reviews. Molecular cell biology · 2025Review
- Lack of dominant-negative activity for tumor-related ZNRF3 missense mutations at endogenous levels.Oncogene · 2025Article
- A phase I dose escalation study of the LRP5 antagonist BI 905681 in patients with advanced and metastatic solid tumors.ESMO open · 2024Article
- E3 ligases RNF43 and ZNRF3 display differential specificity for endocytosis of Frizzled receptors.Life science alliance · 2024Article
- New insights in ubiquitin-dependent Wnt receptor regulation in tumorigenesis.In vitro cellular & developmental biology. Animal · 2024Review
- Zinc Finger Proteins in the War on Gastric Cancer: Molecular Mechanism and Clinical Potential.Cells · 2023Review
- Transcription factor c-Myb: novel prognostic factor in osteosarcoma.Clinical & experimental metastasis · 2022Article
- Receptor control by membrane-tethered ubiquitin ligases in development and tissue homeostasis.Current topics in developmental biology · 2022Article
- Article
- 12-O-Tetradecanoylphorbol-13-acetate increases cardiomyogenesis through PKC/ERK signaling.Scientific reports · 2020Article
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRNF43 and its homolog ZNRF3 are transmembrane E3 ubiquitin ligases frequently mutated in many human cancer types. Their main role relays on the inhibition of canonical Wnt signaling by the negative regulation of frizzled receptors and LRP5/6 co-receptors levels at the plasma membrane. Intracellular RING domains of RNF43/ZNRF3 mediate the key enzymatic activity of these proteins, but the function of the extracellular Protease Associated (PA) fold in the inhibition of Wnt/β-catenin pathway is controversial up-to date, apart from the interaction with secreted antagonists R-spondin family proteins shown by the crystallographic studies.
methodsIn our research we utilised cell-based approaches to study the role of RNF43 lacking PA domain in the canonical Wnt signalling pathway transduction. We developed controlled overexpression (TetON) and CRISPR/Cas9 mediated knock-out models in human cells.
resultsRNF43ΔPA mutant activity impedes canonical Wnt pathway, as manifested by the reduced phosphorylation of LRP6, DVL2 and DVL3 and by the decreased β-catenin-dependent gene expression. Finally, rescue experiments in the CRISPR/Cas9 derived RNF43/ZNRF3 double knock-out cell lines showed that RNFΔPA overexpression is enough to inhibit activation of LRP6 and β-catenin activity as shown by the Western blot and Top flash dual luciferase assays. Moreover, RNF43 variant without PA domain was not sensitive to the R-spondin1 treatment.
conclusionTaken together, our results help to understand better the mode of RNF43 tumor suppressor action and solve some discrepancies present in the field. Video Abstract.
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