| First Author | Keyes WM | Year | 2011 |
| Journal | Cell Stem Cell | Volume | 8 |
| Issue | 2 | Pages | 164-76 |
| PubMed ID | 21295273 | Mgi Jnum | J:168830 |
| Mgi Id | MGI:4939075 | Doi | 10.1016/j.stem.2010.12.009 |
| Citation | Keyes WM, et al. (2011) DeltaNp63alpha Is an Oncogene that Targets Chromatin Remodeler Lsh to Drive Skin Stem Cell Proliferation and Tumorigenesis. Cell Stem Cell 8(2):164-76 |
| abstractText | The p53 homolog p63 is essential for development, yet its role in cancer is not clear. We discovered that p63 deficiency evokes the tumor-suppressive mechanism of cellular senescence, causing a striking absence of stratified epithelia such as the skin. Here we identify the predominant p63 isoform, DeltaNp63alpha, as a protein that bypasses oncogene-induced senescence to drive tumorigenesis in vivo. Interestingly, bypass of senescence promotes stem-like proliferation and maintains survival of the keratin 15-positive stem cell population. Furthermore, we identify the chromatin-remodeling protein Lsh as a new target of DeltaNp63alpha that is an essential mediator of senescence bypass. These findings indicate that DeltaNp63alpha is an oncogene that cooperates with Ras to promote tumor-initiating stem-like proliferation and suggest that Lsh-mediated chromatin-remodeling events are critical to this process. |
