DeltaNp63alpha Is an Oncogene that Targets Chromatin Remodeler Lsh to Drive Skin Stem Cell Proliferation and Tumorigenesis

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. (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)

URL: http://www.ncbi.nlm.nih.gov/pubmed/21295273
DOI: 10.1016/j.stem.2010.12.009

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:
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 Deposited: 07 Feb 2013 15:09
Last Modified: 02 Feb 2017 16:47
PMCID: PMC4373450
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27124

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