Specific recognition of a transcriptional element within the human h-ras protooncogene by the p53 tumor-suppressor

D Spandidos1, V Zoumpourlis, G Zachos

  • 1UNIV CRETE,SCH MED,IRAKLION,GREECE. UNIV PENN,DEPT MOLEC ONCOL,PHILADELPHIA,PA 19104. UNIV PENN,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19104.

Insights

The tumor suppressor p53 protein binds DNA and activates transcription of the c-H-ras gene. This suggests p53 regulates cell growth by controlling genes that promote or suppress proliferation.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • The p53 protein, a nuclear phosphoprotein, is crucial in human cancer, acting as a tumor suppressor.
  • Wild-type p53 regulates cell cycle progression and gene transcription.
  • p53 exhibits sequence-specific DNA binding capabilities.

Purpose of the Study:

  • To investigate the interaction between wild-type p53 and the human c-H-ras gene.
  • To determine if p53 can bind to and activate transcription via sequences within the c-H-ras gene.

Main Methods:

  • In vitro translation of wild-type p53.
  • DNA binding assays to assess p53 affinity for c-H-ras sequences.
  • Reporter plasmid assays to measure transcriptional activation.

Main Results:

  • Wild-type p53 demonstrated high-affinity binding to specific sequences in the first intron of the c-H-ras gene.
  • These c-H-ras sequences function as a bona fide p53 binding element.
  • p53 activated transcription when these elements were included in a reporter plasmid.

Conclusions:

  • p53 directly interacts with and regulates the transcription of the c-H-ras gene.
  • This interaction suggests a mechanism by which p53 influences cellular growth.
  • p53 coordinates the transcription of genes involved in both suppression and promotion of cellular proliferation.

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