| First Author | Bouteille N | Year | 2009 |
| Journal | Oncogene | Volume | 28 |
| Issue | 28 | Pages | 2569-80 |
| PubMed ID | 19465938 | Mgi Jnum | J:153468 |
| Mgi Id | MGI:4365507 | Doi | 10.1038/onc.2009.120 |
| Citation | Bouteille N, et al. (2009) Inhibition of the Wnt/beta-catenin pathway by the WWOX tumor suppressor protein. Oncogene 28(28):2569-80 |
| abstractText | 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. |
