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| Verfasst von: | Giebel, Nicole [VerfasserIn]  |
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| | Jaime-Soguero, Anchel de [VerfasserIn] |
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| | García del Arco, Ana [VerfasserIn] |
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| | Landry, Jonathan [VerfasserIn] |
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| | Tietje, Marlene [VerfasserIn] |
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| | Villacorta, Laura [VerfasserIn] |
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| | Benes, Vladimir [VerfasserIn] |
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| | Fernández-Sáiz, Vanesa [VerfasserIn] |
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| | Acebron, Sergio P. [VerfasserIn] |
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| Titel: | USP42 protects ZNRF3/RNF43 from R-spondin-dependent clearance and inhibits Wnt signalling |
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| Verf.angabe: | Nicole Giebel, Anchel de Jaime-Soguero, Ana García del Arco, Jonathan JM Landry, Marlene Tietje, Laura Villacorta, Vladimir Benes, Vanesa Fernández-Sáiz & Sergio P Acebrón |
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| E-Jahr: | 2021 |
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| Jahr: | 30 March 2021 |
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| Umfang: | 16 S. |
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| Fussnoten: | Gesehen am 12.01.2022 |
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| Titel Quelle: | Enthalten in: European Molecular Biology OrganizationEMBO reports |
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| Ort Quelle: | Heidelberg : EMBO Press, 2000 |
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| Jahr Quelle: | 2021 |
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| Band/Heft Quelle: | 22(2021), 5, Artikel-ID e51415, Seite 1-16 |
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| ISSN Quelle: | 1469-3178 |
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| Abstract: | Abstract The tumour suppressors RNF43 and ZNRF3 play a central role in development and tissue homeostasis by promoting the turnover of the Wnt receptors LRP6 and Frizzled (FZD). The stem cell growth factor R-spondin induces auto-ubiquitination and membrane clearance of ZNRF3/RNF43 to promote Wnt signalling. However, the deubiquitinase stabilising ZNRF3/RNF43 at the plasma membrane remains unknown. Here, we show that the USP42 antagonises R-spondin by protecting ZNRF3/RNF43 from ubiquitin-dependent clearance. USP42 binds to the Dishevelled interacting region (DIR) of ZNRF3 and stalls the R-spondin-LGR4-ZNRF3 ternary complex by deubiquitinating ZNRF3. Accordingly, USP42 increases the turnover of LRP6 and Frizzled (FZD) receptors and inhibits Wnt signalling. Furthermore, we show that USP42 functions as a roadblock for paracrine Wnt signalling in colon cancer cells and mouse small intestinal organoids. We provide new mechanistic insights into the regulation R-spondin and conclude that USP42 is crucial for ZNRF3/RNF43 stabilisation at the cell surface. |
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| DOI: | doi:10.15252/embr.202051415 |
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| URL: | kostenfrei: Volltext: https://doi.org/10.15252/embr.202051415 |
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| | kostenfrei: Volltext: https://www.embopress.org/doi/full/10.15252/embr.202051415 |
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| | DOI: https://doi.org/10.15252/embr.202051415 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | colorectal cancer |
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| | deubiquitination |
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| | EMT |
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| | LGR4/5/6 |
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| | mouse intestinal organoids |
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| K10plus-PPN: | 1785806092 |
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| Verknüpfungen: | → Zeitschrift |
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| Lokale URL UB: |  Zum Volltext |
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USP42 protects ZNRF3/RNF43 from R-spondin-dependent clearance and inhibits Wnt signalling / Giebel, Nicole [VerfasserIn]; 30 March 2021 (Online-Ressource)
