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WIKI4, a novel inhibitor of tankyrase and Wnt/ß-catenin signaling.

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.

SUBMITTER: James RG

PROVIDER: S-EPMC3515623 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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WIKI4, a novel inhibitor of tankyrase and Wnt/ß-catenin signaling.

James Richard G RG Davidson Kathryn C KC Bosch Katherine A KA Biechele Travis L TL Robin Nicholas C NC Taylor Russell J RJ Major Michael B MB Camp Nathan D ND Fowler Kerry K Martins Timothy J TJ Moon Randall T RT

PloS one 20121205 12

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 ...[more]

PMID: 23227175

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