Feng, Z., Jin, S., Zupnick, A., Hoh, J., De Stanchina, E., Lowe, S. W., Prives, C., Levine, A. J. (2006) p53 tumor suppressor protein regulates the levels of huntingtin gene expression. Oncogene, 25 (1). pp. 1-7. ISSN 09509232
Abstract
The p53 protein is a transcription factor that integrates various cellular stress signals. The accumulation of the mutant huntingtin protein with an expanded polyglutamine tract plays a central role in the pathology of human Huntington's disease. We found that the huntingtin gene contains multiple putative p53-responsive elements and p53 binds to these elements both in vivo and in vitro. p53 activation in cultured human cells, either by a temperature-sensitive mutant p53 protein or by gamma-irradiation (?-irradiation), increases huntingtin mRNA and protein expression. Similarly, murine huntingtin also contains multiple putative p53-responsive elements and its expression is induced by p53 activation in cultured cells. Moreover, ?-irradiation, which activates p53, increases huntingtin gene expression in the striatum and cortex of mouse brain, the major pathological sites for Huntington's disease, in p53+/+ but not the isogenic p53-/- mice. These results demonstrate that p53 protein can regulate huntingtin expression at transcriptional level, and suggest that a p53 stress response could be a modulator of the process of Huntington's disease. © 2006 Nature Publishing Group. All rights reserved.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | huntingtin protein p53 tumor suppressor protein gene expression protein function transcription regulation Gene Expression Regulation Neoplastic Animalia Murinae |
| Subjects: | diseases & disorders > cancer > cancer types > huntington's disease bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > mRNA dynamics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > p53 bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > transcription factor |
| CSHL Authors: | |
| Communities: | CSHL labs > Lowe lab |
| Depositing User: | CSHL Librarian |
| Date: | 2006 |
| Date Deposited: | 15 Dec 2011 18:50 |
| Last Modified: | 13 Apr 2018 16:12 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/22790 |
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