| First Author | Chen Y | Year | 2016 |
| Journal | EMBO J | Volume | 35 |
| Issue | 6 | Pages | 668-84 |
| PubMed ID | 26912724 | Mgi Jnum | J:231684 |
| Mgi Id | MGI:5774598 | Doi | 10.15252/embj.201592810 |
| Citation | Chen Y, et al. (2016) Wnt-induced deubiquitination FoxM1 ensures nucleus beta-catenin transactivation. EMBO J 35(6):668-84 |
| abstractText | A key step of Wnt signaling activation is the recruitment of beta-catenin to the Wnt target-gene promoter in the nucleus, but its mechanisms are largely unknown. Here, we identified FoxM1 as a novel target of Wnt signaling, which is essential for beta-catenin/TCF4 transactivation. GSK3 phosphorylates FoxM1 on serine 474 which induces FoxM1 ubiquitination mediated by FBXW7. Wnt signaling activation inhibits FoxM1 phosphorylation by GSK3-Axin complex and leads to interaction between FoxM1 and deubiquitinating enzyme USP5, thereby deubiquitination and stabilization of FoxM1. FoxM1 accumulation in the nucleus promotes recruitment of beta-catenin to Wnt target-gene promoter and activates the Wnt signaling pathway by protecting the beta-catenin/TCF4 complex from ICAT inhibition. Subsequently, the USP5-FoxM1 axis abolishes the inhibitory effect of ICAT and is required for Wnt-mediated tumor cell proliferation. Therefore, Wnt-induced deubiquitination of FoxM1 represents a novel and critical mechanism for controlling canonical Wnt signaling and cell proliferation. |
