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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.  Nat. Commun. 7(): 11430.
FlyBase ID
FBrf0232204
Publication Type
Research paper
Abstract

Wnt/β-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.

PubMed ID
PubMed Central ID
PMC4857404 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Nat. Commun.
    Title
    Nature communications
    ISBN/ISSN
    2041-1723
    Data From Reference
    Alleles (12)
    Gene Groups (1)
    Genes (5)
    Cell Lines (1)
    Natural transposons (1)
    Experimental Tools (4)
    Transgenic Constructs (8)