| First Author | Zhang L | Year | 2011 |
| Journal | Mol Biol Cell | Volume | 22 |
| Issue | 9 | Pages | 1617-24 |
| PubMed ID | 21411632 | Mgi Jnum | J:182968 |
| Mgi Id | MGI:5317248 | Doi | 10.1091/mbc.E10-12-0985 |
| Citation | Zhang L, et al. (2011) Fas-associated factor 1 antagonizes Wnt signaling by promoting beta-catenin degradation. Mol Biol Cell 22(9):1617-24 |
| abstractText | The canonical Wnt pathway plays an important role in the regulation of cell proliferation and differentiation. Activation of this signaling pathway causes disruption of the Axin/adenomatous polyposis coli/glycogen synthase kinase 3beta complex, resulting in stabilization of beta-catenin and its association with lymphoid enhancer factor/T-cell factor in the nucleus. Here, we identify Fas-associated factor 1 (FAF1) as a negative regulator of Wnt/beta-catenin signaling. We found overexpression of FAF1 to strongly inhibit Wnt-induced transcriptional reporter activity and to counteract Wnt-induced beta-catenin accumulation. Moreover, knockdown of FAF1 resulted in an increase in beta-catenin levels and in activation of Wnt/beta-catenin-induced transcription. FAF1 was found to interact with beta-catenin upon inhibition of proteasome. Ectopic expression of FAF1 promoted beta-catenin degradation by enhancing its polyubiquitination. Functional studies in C2C12 myoblasts and KS483 preosteoblastic cells showed that FAF1 depletion resulted in activation of endogenous Wnt-induced genes and enhanced osteoblast differentiation, whereas FAF1 overexpression had the opposite effect. These results identify FAF1 as a novel inhibitory factor of canonical Wnt signaling pathway. |
