Wnt pathway activation by ADP-ribosylation

Eungi Yang, Ofelia Tacchelly-Benites, Zhenghan Wang, Michael P. Randall, Ai Tian, Hassina Benchabane, Sarah Freemantle, Claudio Pikielny, Nicholas S. Tolwinski, Ethan Lee, Yashi Ahmed

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number11430
JournalNature communications
Volume7
DOIs
StatePublished - May 3 2016
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Fingerprint Dive into the research topics of 'Wnt pathway activation by ADP-ribosylation'. Together they form a unique fingerprint.

Cite this