p53 tumor suppressor protein regulates the levels of huntingtin gene expression

Oncogene. 2006 Jan 5;25(1):1-7. doi: 10.1038/sj.onc.1209021.


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.

MeSH terms

  • Animals
  • Blotting, Northern
  • Blotting, Western
  • Cell Line, Tumor
  • Chromatin Immunoprecipitation
  • DNA Damage
  • Gamma Rays
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Huntingtin Protein
  • Huntington Disease / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Mutation
  • Nerve Tissue Proteins / biosynthesis*
  • Nerve Tissue Proteins / genetics
  • Nuclear Proteins / biosynthesis*
  • Nuclear Proteins / genetics
  • RNA, Messenger / metabolism
  • Response Elements
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Temperature
  • Time Factors
  • Transcription, Genetic
  • Tumor Suppressor Protein p53 / metabolism
  • Tumor Suppressor Protein p53 / physiology*


  • HTT protein, human
  • Huntingtin Protein
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • RNA, Messenger
  • Tumor Suppressor Protein p53