Keyes, W. M. , Pecoraro, M., Aranda, V., Vernersson-Lindahl, E., Li, W., Vogel, H., Guo, X., Garcia, E. L., Michurina, T. V., Enikolopov, G. N., Muthuswamy, S. K., Mills, A. A.
(February 2011)
DeltaNp63alpha Is an Oncogene that Targets Chromatin Remodeler Lsh to Drive Skin Stem Cell Proliferation and Tumorigenesis.
Cell Stem Cell, 8 (2).
pp. 164-76.
ISSN 1875-9777 (Electronic)
Abstract
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.
| Item Type: |
Paper
|
| Subjects: |
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > Chromatin dynamics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > oncogene
therapies > stem cells |
| CSHL Authors: |
Aranda, Victoria 
Enikolopov, Grigori N.
Garcia, Elvin L.
Guo, Xuecui
Keyes, William M.
Li, Wangzhi
Michurina, Tatyana V.
Mills, Alea A.
Muthuswamy, Senthil K.
Vernersson Lindahl, Emma
|
| Communities: |
CSHL Cancer Center Program > Cancer Genetics
CSHL Cancer Center Program > Signal Transduction
CSHL Cancer Center Shared Resources > Animal Services
CSHL Cancer Center Shared Resources > Microscopy Service
CSHL labs > Enikopolov lab
CSHL labs > Mills lab
CSHL labs > Muthuswamy lab
CSHL Cancer Center Shared Resources > Functional Genomics and Genetics Service |
| Depositing User: |
Matt Covey
|
| Date: |
4 February 2011 |
| Date Deposited: |
07 Feb 2013 15:09 |
| Last Modified: |
02 Feb 2017 16:47 |
| PMCID: |
PMC4373450 |
| Related URLs: |
|
| URI: |
https://repository.cshl.edu/id/eprint/27124 |
Actions (login required)
 |
Administrator's edit/view item |