| First Author | Feng Z | Year | 2006 |
| Journal | Oncogene | Volume | 25 |
| Issue | 1 | Pages | 1-7 |
| PubMed ID | 16278683 | Mgi Jnum | J:104350 |
| Mgi Id | MGI:3611699 | Doi | 10.1038/sj.onc.1209021 |
| Citation | Feng Z, et al. (2006) p53 tumor suppressor protein regulates the levels of huntingtin gene expression. Oncogene 25(1):1-7 |
| abstractText | 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 (gamma-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, gamma-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. |
