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DNA damage signalling recruits RREB-1 to the p53 tumour suppressor promoter

Hanshao Liu1, Hoi Chin Hew, Zheng-Guang Lu

  • 1Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.

The Biochemical Journal
|June 30, 2009
PubMed

Insights

Ras-responsive-element-binding protein-1 (RREB-1) activates the p53 tumor suppressor gene, crucial for DNA damage response. RREB-1 is essential for p53 expression and its downstream target genes, impacting apoptosis.

Area of Science:

  • Molecular biology
  • Cancer research
  • Gene regulation

Background:

  • The p53 tumor suppressor gene is critical for cellular responses to DNA damage.
  • The precise molecular mechanisms regulating p53 gene transcription are not fully understood.
  • Understanding p53 regulation is vital for developing cancer therapies.

Purpose of the Study:

  • To investigate the role of Ras-responsive-element-binding protein-1 (RREB-1) in regulating p53 gene expression.
  • To elucidate the molecular basis of RREB-1's interaction with the p53 promoter.
  • To determine the functional significance of RREB-1-mediated p53 regulation in DNA damage response and apoptosis.

Main Methods:

  • Chromatin immunoprecipitation assays to assess RREB-1 binding to the p53 promoter.
  • Quantitative real-time PCR and Western blotting to measure mRNA and protein levels of p53 and its target genes.
  • RNA interference (RNAi) to silence RREB-1 expression.
  • Assessment of apoptosis following genotoxic stress.

Main Results:

  • RREB-1 directly binds to the p53 core promoter element and enhances p53 transcription.
  • Silencing RREB-1 leads to a significant decrease in both p53 mRNA and protein levels.
  • RREB-1-dependent p53 activation is necessary for the expression of p53 target genes involved in DNA damage response.
  • RREB-1 mediates apoptosis in response to genotoxic stress in a p53-dependent manner.

Conclusions:

  • RREB-1 is a key transcriptional activator of the p53 tumor suppressor gene.
  • RREB-1 plays a crucial role in the p53-mediated DNA damage response pathway.
  • RREB-1's function in p53 regulation highlights its potential as a therapeutic target in cancer.

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