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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 |
| Appears in Collections: | Elements Staff Publications |
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