USP42 protects ZNRF3/RNF43 from R-spondin-dependent clearance and inhibits Wnt signalling
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 sig...
Gespeichert in:
| Hauptverfasser: | , , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
30 March 2021
|
| In: |
EMBO reports
Year: 2021, Jahrgang: 22, Heft: 5, Pages: 1-16 |
| ISSN: | 1469-3178 |
| DOI: | 10.15252/embr.202051415 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.15252/embr.202051415 Verlag, kostenfrei, Volltext: https://www.embopress.org/doi/full/10.15252/embr.202051415 
|
| Verfasserangaben: | 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 |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1785806092 | ||
| 003 | DE-627 | ||
| 005 | 20230320073737.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 220112s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.15252/embr.202051415 |2 doi | |
| 035 | |a (DE-627)1785806092 | ||
| 035 | |a (DE-599)KXP1785806092 | ||
| 035 | |a (OCoLC)1341436767 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 32 |2 sdnb | ||
| 100 | 1 | |a Giebel, Nicole |d 1993- |e VerfasserIn |0 (DE-588)1249229138 |0 (DE-627)1785768174 |4 aut | |
| 245 | 1 | 0 | |a USP42 protects ZNRF3/RNF43 from R-spondin-dependent clearance and inhibits Wnt signalling |c 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 |
| 264 | 1 | |c 30 March 2021 | |
| 300 | |a 16 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 12.01.2022 | ||
| 520 | |a 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. | ||
| 650 | 4 | |a colorectal cancer | |
| 650 | 4 | |a deubiquitination | |
| 650 | 4 | |a EMT | |
| 650 | 4 | |a LGR4/5/6 | |
| 650 | 4 | |a mouse intestinal organoids | |
| 700 | 1 | |a Jaime-Soguero, Anchel de |e VerfasserIn |0 (DE-588)1249232031 |0 (DE-627)1785809423 |4 aut | |
| 700 | 1 | |a García del Arco, Ana |e VerfasserIn |0 (DE-588)1136887784 |0 (DE-627)893681202 |0 (DE-576)490909892 |4 aut | |
| 700 | 1 | |a Landry, Jonathan |e VerfasserIn |0 (DE-588)1032005459 |0 (DE-627)737808799 |0 (DE-576)37974256X |4 aut | |
| 700 | 1 | |a Tietje, Marlene |e VerfasserIn |4 aut | |
| 700 | 1 | |a Villacorta, Laura |e VerfasserIn |4 aut | |
| 700 | 1 | |a Benes, Vladimir |e VerfasserIn |0 (DE-588)1155743911 |0 (DE-627)1017952639 |0 (DE-576)501828893 |4 aut | |
| 700 | 1 | |a Fernández-Sáiz, Vanesa |e VerfasserIn |4 aut | |
| 700 | 1 | |a Acebron, Sergio P. |e VerfasserIn |0 (DE-588)1137651474 |0 (DE-627)895022087 |0 (DE-576)491696272 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |a European Molecular Biology Organization |t EMBO reports |d [London] : Nature Publishing Group UK, 2000 |g 22(2021), 5, Artikel-ID e51415, Seite 1-16 |h Online-Ressource |w (DE-627)320645622 |w (DE-600)2025376-X |w (DE-576)095092153 |x 1469-3178 |7 nnas |
| 773 | 1 | 8 | |g volume:22 |g year:2021 |g number:5 |g elocationid:e51415 |g pages:1-16 |g extent:16 |a USP42 protects ZNRF3/RNF43 from R-spondin-dependent clearance and inhibits Wnt signalling |
| 856 | 4 | 0 | |u https://doi.org/10.15252/embr.202051415 |x Verlag |x Resolving-System |z kostenfrei |3 Volltext |
| 856 | 4 | 0 | |u https://www.embopress.org/doi/full/10.15252/embr.202051415 |x Verlag |z kostenfrei |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20220112 | ||
| 993 | |a Article | ||
| 994 | |a 2021 | ||
| 998 | |g 1137651474 |a Acebron, Sergio P. |m 1137651474:Acebron, Sergio P. |d 140000 |e 140000PA1137651474 |k 0/140000/ |p 9 |y j | ||
| 998 | |g 1155743911 |a Benes, Vladimir |m 1155743911:Benes, Vladimir |p 7 | ||
| 998 | |g 1032005459 |a Landry, Jonathan |m 1032005459:Landry, Jonathan |p 4 | ||
| 998 | |g 1136887784 |a García del Arco, Ana |m 1136887784:García del Arco, Ana |p 3 | ||
| 998 | |g 1249232031 |a Jaime-Soguero, Anchel de |m 1249232031:Jaime-Soguero, Anchel de |d 700000 |d 721000 |e 700000PJ1249232031 |e 721000PJ1249232031 |k 0/700000/ |k 1/700000/721000/ |p 2 | ||
| 998 | |g 1249229138 |a Giebel, Nicole |m 1249229138:Giebel, Nicole |d 700000 |d 721000 |e 700000PG1249229138 |e 721000PG1249229138 |k 0/700000/ |k 1/700000/721000/ |p 1 |x j | ||
| 999 | |a KXP-PPN1785806092 |e 4033870725 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"physDesc":[{"extent":"16 S."}],"relHost":[{"title":[{"title_sort":"EMBO reports","title":"EMBO reports"}],"pubHistory":["1.2000 -"],"part":{"volume":"22","text":"22(2021), 5, Artikel-ID e51415, Seite 1-16","extent":"16","year":"2021","issue":"5","pages":"1-16"},"disp":"European Molecular Biology OrganizationEMBO reports","type":{"media":"Online-Ressource","bibl":"periodical"},"note":["Fortsetzung der Druck-Ausgabe","Gesehen am 11.03.25"],"language":["eng"],"corporate":[{"role":"aut","display":"European Molecular Biology Organization","roleDisplay":"VerfasserIn"}],"recId":"320645622","origin":[{"publisherPlace":"[London] ; Heidelberg ; Oxford [u.a.] ; London [u.a.] ; Hoboken, NJ [u.a.]","dateIssuedDisp":"[2000]-","publisher":"Nature Publishing Group UK ; EMBO Press ; Oxford Univ. Press ; Nature Publishing Group ; Wiley"}],"id":{"issn":["1469-3178"],"zdb":["2025376-X"],"doi":["10.1002/(ISSN)1469-3178"],"eki":["320645622"]},"name":{"displayForm":["European Molecular Biology Organization"]},"physDesc":[{"extent":"Online-Ressource"}]}],"origin":[{"dateIssuedDisp":"30 March 2021","dateIssuedKey":"2021"}],"id":{"doi":["10.15252/embr.202051415"],"eki":["1785806092"]},"name":{"displayForm":["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"]},"note":["Gesehen am 12.01.2022"],"type":{"media":"Online-Ressource","bibl":"article-journal"},"language":["eng"],"recId":"1785806092","title":[{"title":"USP42 protects ZNRF3/RNF43 from R-spondin-dependent clearance and inhibits Wnt signalling","title_sort":"USP42 protects ZNRF3/RNF43 from R-spondin-dependent clearance and inhibits Wnt signalling"}],"person":[{"roleDisplay":"VerfasserIn","display":"Giebel, Nicole","role":"aut","family":"Giebel","given":"Nicole"},{"display":"Jaime-Soguero, Anchel de","roleDisplay":"VerfasserIn","role":"aut","family":"Jaime-Soguero","given":"Anchel de"},{"family":"García del Arco","given":"Ana","roleDisplay":"VerfasserIn","display":"García del Arco, Ana","role":"aut"},{"family":"Landry","given":"Jonathan","display":"Landry, Jonathan","roleDisplay":"VerfasserIn","role":"aut"},{"role":"aut","display":"Tietje, Marlene","roleDisplay":"VerfasserIn","given":"Marlene","family":"Tietje"},{"family":"Villacorta","given":"Laura","display":"Villacorta, Laura","roleDisplay":"VerfasserIn","role":"aut"},{"given":"Vladimir","family":"Benes","role":"aut","roleDisplay":"VerfasserIn","display":"Benes, Vladimir"},{"roleDisplay":"VerfasserIn","display":"Fernández-Sáiz, Vanesa","role":"aut","family":"Fernández-Sáiz","given":"Vanesa"},{"family":"Acebron","given":"Sergio P.","display":"Acebron, Sergio P.","roleDisplay":"VerfasserIn","role":"aut"}]} | ||
| SRT | |a GIEBELNICOUSP42PROTE3020 | ||