Please use this identifier to cite or link to this item: https://doi.org/10.1038/ncomms11430
Title: Wnt pathway activation by ADP-ribosylation
Authors: Yang, E
Tacchelly-Benites, O
Wang, Z
Randall, M.P
Tian, A
Benchabane, H
Freemantle, S
Pikielny, C
Tolwinski, N.S 
Lee, E
Ahmed, Y
Keywords: adenosine diphosphate
axin
low density lipoprotein receptor related protein 6
Wnt protein
adenosine diphosphate ribose
axin
axin protein, Drosophila
beta catenin
CTNNB1 protein, human
Drosophila protein
LRP6 protein, human
tankyrase
TNKS protein, human
Wnt3a protein
cancer
cells and cell components
fly
metazoan
protein
adenosine diphosphate ribosylation
Article
concentration (parameters)
controlled study
Drosophila
embryo
human
human cell
nonhuman
protein degradation
protein protein interaction
Wnt signaling pathway
amino acid sequence
animal
cytology
Drosophila melanogaster
drug effects
embryology
gene expression regulation
genetics
HEK293 cell line
lymphocyte
metabolism
molecular genetics
nonmammalian embryo
sequence alignment
transgenic animal
tumor cell line
Wnt signaling pathway
Metazoa
Adenosine Diphosphate Ribose
Amino Acid Sequence
Animals
Animals, Genetically Modified
Axin Protein
beta Catenin
Cell Line, Tumor
Drosophila melanogaster
Drosophila Proteins
Embryo, Nonmammalian
Gene Expression Regulation, Developmental
HEK293 Cells
Humans
Low Density Lipoprotein Receptor-Related Protein-6
Lymphocytes
Molecular Sequence Data
Proteolysis
Sequence Alignment
Tankyrases
Wnt Signaling Pathway
Wnt3A Protein
Issue Date: 2016
Publisher: Nature Publishing Group
Citation: Yang, E, Tacchelly-Benites, O, Wang, Z, Randall, M.P, Tian, A, Benchabane, H, Freemantle, S, Pikielny, C, Tolwinski, N.S, Lee, E, Ahmed, Y (2016). Wnt pathway activation by ADP-ribosylation. Nature Communications 7 : 11430. ScholarBank@NUS Repository. https://doi.org/10.1038/ncomms11430
Rights: Attribution 4.0 International
Abstract: Wnt/?-catenin signalling directs fundamental processes during metazoan development and can be aberrantly activated in cancer. Wnt stimulation induces the recruitment of the scaffold protein Axin from an inhibitory destruction complex to a stimulatory signalosome. Here we analyse the early effects of Wnt on Axin and find that the ADP-ribose polymerase Tankyrase (Tnks) - known to target Axin for proteolysis - regulates Axin's rapid transition following Wnt stimulation. We demonstrate that the pool of ADP-ribosylated Axin, which is degraded under basal conditions, increases immediately following Wnt stimulation in both Drosophila and human cells. ADP-ribosylation of Axin enhances its interaction with the Wnt co-receptor LRP6, an essential step in signalosome assembly. We suggest that in addition to controlling Axin levels, Tnks-dependent ADP-ribosylation promotes the reprogramming of Axin following Wnt stimulation; and propose that Tnks inhibition blocks Wnt signalling not only by increasing destruction complex activity, but also by impeding signalosome assembly. © 2016, Nature Publishing Group. All rights reserved.
Source Title: Nature Communications
URI: https://scholarbank.nus.edu.sg/handle/10635/182476
ISSN: 2041-1723
DOI: 10.1038/ncomms11430
Rights: Attribution 4.0 International
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