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Inhibition of the Wnt/Β-catenin pathway by the WWOX tumor suppressor protein

Oncogene, ISSN: 0950-9232, Vol: 28, Issue: 28, Page: 2569-2580
2009
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Article Description

The WWOX gene encodes a candidate tumor suppressor protein (WWOX) implicated in a variety of human diseases such as cancer. To better understand the molecular mechanisms of WWOX action, we investigated novel partners of this protein. Using the two-hybrid system and a coimmunoprecipitation assay, we observed a physical association between WWOX and the Dishevelled protein (Dvl) family signaling elements involved in the Wnt/Β-catenin pathway. We found that enforced WWOX expression inhibited, and inhibition of endogenous WWOX expression stimulated the transcriptional activity of the Wnt/Β-catenin pathway. Inhibition of endogenous WWOX expression also enhanced the effect of Wnt-3a on Β-catenin stability. Moreover, we observed the sequestration of Dvl-2 wild type and Dvl-2NESm, a mutated form of Dvl-2 predominantly localized in the nucleus, in the cytoplasm compartment by WWOX. Our results indicate that WWOX is a novel inhibitor of the Wnt/Β-catenin pathway. WWOX would act, at least in part, by preventing the nuclear import of the Dvl proteins. © 2009 Macmillan Publishers Limited.

Bibliographic Details

N. Bouteille; K. Driouch; P. E. Hage; S. Sin; R. Lidereau; F. Lallemand; E. Formstecher; J. Camonis

Springer Science and Business Media LLC

Biochemistry, Genetics and Molecular Biology

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