WIKI4, a Novel Inhibitor of Tankyrase and Wnt/ß-Catenin Signaling
Loading...
Citations
Web of Science:
Altmetric:
Altmetric::
Download
Associated Records
Authors
File Licence
Editors
Date
2012-12-05
Source Title
PLoS ONE
Journal Title
Journal ISSN
Volume Title
Publisher
PUBLIC LIBRARY SCIENCE
Melbourne Authors
Affiliation
Medical Biology (W.E.H.I.)
Document Type
Journal Article
Subject Code
Citation
James, R. G., Davidson, K. C., Bosch, K. A., Biechele, T. L., Robin, N. C., Taylor, R. J., Major, M. B., Camp, N. D., Fowler, K., Martins, T. J. & Moon, R. T. (2012). WIKI4, a Novel Inhibitor of Tankyrase and Wnt/ß-Catenin Signaling. Plos One, 7 (12), https://doi.org/10.1371/journal.pone.0050457.
Access Status
Open Access
Access URL
Open Access URL
Open Access at PMC
Linked Resource URL
NHMRC Grant Code
ARC Grant Code
Description
Abstract
The Wnt/ß-catenin signaling pathway controls important cellular events during development and often contributes to disease when dysregulated. Using high throughput screening we have identified a new small molecule inhibitor of Wnt/ß-catenin signaling, WIKI4. WIKI4 inhibits expression of ß-catenin target genes and cellular responses to Wnt/ß-catenin signaling in cancer cell lines as well as in human embryonic stem cells. Furthermore, we demonstrate that WIKI4 mediates its effects on Wnt/ß-catenin signaling by inhibiting the enzymatic activity of TNKS2, a regulator of AXIN ubiquitylation and degradation. While TNKS has previously been shown to be the target of small molecule inhibitors of Wnt/ß-catenin signaling, WIKI4 is structurally distinct from previously identified TNKS inhibitors.