p53 tumor suppressor protein regulates the levels of huntingtin gene expression

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

URL: https://www.ncbi.nlm.nih.gov/pubmed/16278683
DOI: 10.1038/sj.onc.1209021

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: http://repository.cshl.edu/id/eprint/22790

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