Protease associated domain of RNF43 is not necessary for the suppression of Wnt/beta-catenin signaling in human cells
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F20%3A00540114" target="_blank" >RIV/68081707:_____/20:00540114 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14310/20:00114371
Result on the web
<a href="https://biosignaling.biomedcentral.com/articles/10.1186/s12964-020-00559-0" target="_blank" >https://biosignaling.biomedcentral.com/articles/10.1186/s12964-020-00559-0</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1186/s12964-020-00559-0" target="_blank" >10.1186/s12964-020-00559-0</a>
Alternative languages
Result language
angličtina
Original language name
Protease associated domain of RNF43 is not necessary for the suppression of Wnt/beta-catenin signaling in human cells
Original language description
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/beta-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.ResultsRNF43 Delta PA mutant activity impedes canonical Wnt pathway, as manifested by the reduced phosphorylation of LRP6, DVL2 and DVL3 and by the decreased beta-catenin-dependent gene expression. Finally, rescue experiments in the CRISPR/Cas9 derived RNF43/ZNRF3 double knock-out cell lines showed that RNF Delta PA overexpression is enough to inhibit activation of LRP6 and beta-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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10601 - Cell biology
Result continuities
Project
<a href="/en/project/GX19-28347X" target="_blank" >GX19-28347X: Molecular and functional analysis of casein kinase 1 biology</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Cell communication and signaling : CCS
ISSN
1478-811X
e-ISSN
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Volume of the periodical
18
Issue of the periodical within the volume
1
Country of publishing house
GB - UNITED KINGDOM
Number of pages
12
Pages from-to
91
UT code for WoS article
000542292400001
EID of the result in the Scopus database
2-s2.0-85086424863