WIKI4, a novel inhibitor of tankyrase and Wnt/ß-catenin signaling.
oleh: Richard G James, Kathryn C Davidson, Katherine A Bosch, Travis L Biechele, Nicholas C Robin, Russell J Taylor, Michael B Major, Nathan D Camp, Kerry Fowler, Timothy J Martins, Randall T Moon
| Format: | Article |
|---|---|
| Diterbitkan: | Public Library of Science (PLoS) 2012-01-01 |
Deskripsi
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.