Format

Send to

Choose Destination
Nat Commun. 2016 May 3;7:11430. doi: 10.1038/ncomms11430.

Wnt pathway activation by ADP-ribosylation.

Author information

1
Department of Genetics and the Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth College, Hanover, New Hampshire 03755, USA.
2
Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth College, Hanover, New Hampshire 03755, USA.
3
Department of Biological Sciences, Yale-NUS College, National University of Singapore, Singapore 138615, Singapore.
4
Department of Cell and Developmental Biology, Vanderbilt Ingram Cancer Center, and Vanderbilt Institute of Chemical Biology, Nashville, Tennessee 37232, USA.

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.

PMID:
27138857
PMCID:
PMC4857404
DOI:
10.1038/ncomms11430
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Grant support

Publication types

MeSH terms

Substances

Grant support

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center