Protease associated domain of RNF43 is not necessary for the suppression of Wnt/β-catenin signaling in human cells.

Cell Communication and Signaling : CCS
Tomasz Radaszkiewicz, Vitezslav Bryja

Abstract

RNF43 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. In 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. RNF43ΔPA 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 an...Continue Reading

References

Jan 9, 2007·Proceedings of the National Academy of Sciences of the United States of America·Takahiko Matsuda, Constance L Cepko
Mar 24, 2012·Genome Biology·Wim B M de LauHans C Clevers
Oct 26, 2012·The Journal of Pathology·Georgina L RylandIan G Campbell
Jan 5, 2013·Science·Prashant MaliGeorge M Church
Jun 13, 2013·Genes & Development·Po-Han ChenXiaolin He
Jun 13, 2013·Genes & Development·Dongli WangXinquan Wang
Jul 31, 2013·Structure·Kai XuDimitar B Nikolov
Dec 3, 2013·The Journal of Pathology·Yuchen JiaoLaura D Wood
Feb 18, 2014·Genes & Development·Wim de LauHans Clevers
Oct 27, 2014·Nature Genetics·Marios GiannakisLevi A Garraway
Apr 1, 2015·Molecular and Cellular Biology·Tadasuke TsukiyamaShigetsugu Hatakeyama
May 6, 2015·Progress in Biophysics and Molecular Biology·Matthias Zebisch, E Yvonne Jones
Dec 3, 2016·Nucleic Acids Research·Simon A ForbesPeter J Campbell
Jul 5, 2017·Molecular and Cellular Biology·Petra PaclíkováVítězslav Bryja
Feb 7, 2018·ELife·Andres M Lebensohn, Rajat Rohatgi
Mar 31, 2018·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Stephanie Grainger, Karl Willert
Jun 28, 2018·Development·Katrin E WieseRenée van Amerongen

❮ Previous
Next ❯

Citations

Sep 29, 2020·Scientific Reports·Katarzyna Anna RadaszkiewiczJiří Pachernik
Feb 12, 2021·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Tadasuke TsukiyamaShigetsugu Hatakeyama
Jun 4, 2021·Cellular Signalling·Petra PaclíkováVítězslav Bryja
Jan 8, 2022·Clinical & Experimental Metastasis·Kamila ŘíhováPetr Beneš

❮ Previous
Next ❯

Methods Mentioned

BETA
ubiquitination
co-immunoprecipitation assay
surface plasmon resonance
PCR
co-immunoprecipitation

Software Mentioned

LAS X Life Science ( Leica )
GraphPad Prism
ImageJ

Related Concepts

Related Feeds

CRISPR (general)

Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). CRISPR-Cas system enables the editing of genes to create or correct mutations. Discover the latest research on CRISPR here.

CRISPR for Genome Editing

Genome editing technologies enable the editing of genes to create or correct mutations. Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). Here is the latest research on the use of CRISPR-Cas system in gene editing.

Related Papers

Molecular and Cellular Biology
Tadasuke TsukiyamaShigetsugu Hatakeyama
Journal of Clinical Pathology
Stefano Serra, Runjan Chetty
Proceedings of the National Academy of Sciences of the United States of America
Xiaomo JiangFeng Cong
© 2022 Meta ULC. All rights reserved