期刊
ONCOGENE
卷 28, 期 28, 页码 2569-2580出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2009.120
关键词
WWOX; dishevelled; Wnt; beta-catenin; signaling pathway
资金
- GenHomme Network [02490-6088]
- Institut Curie
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/beta-catenin pathway. We found that enforced WWOX expression inhibited, and inhibition of endogenous WWOX expression stimulated the transcriptional activity of the Wnt/beta-catenin pathway. Inhibition of endogenous WWOX expression also enhanced the effect of Wnt-3a on beta-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/beta-catenin pathway. WWOX would act, at least in part, by preventing the nuclear import of the Dvl proteins. Oncogene (2009) 28, 2569-2580; doi: 10.1038/onc.2009.120; published online 25 May 2009
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