Comparative binding of p53 to its promoter and DNA recognition elements

Richard L. Weinberg, Dmitry B. Veprintsev, Mark Bycroft, Alan R. Fersht*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

144 Scopus citations

Abstract

Tumor suppressor p53 is a transcription factor that transactivates a wide range of genes, including those in DNA repair, cell cycle arrest, apoptosis and its own degradation. To estimate the role of selectivity in binding to its promoters, we measured the binding affinities of a tetrameric p53 construct (p53CT) in vitro with 20 of its recognition elements from a variety of representative genes. The binding of full length p53 to four representative sequences exactly paralleled the affinities to p53CT. The binding of p53 to different recognition elements was co-operative and the affinities varied by up to 50-fold. p53 bound with high affinity to the recognition elements of all the genes involved in cell cycle arrest and some of the genes in apoptosis. All of the lower affinity-binding sites were in genes involved in apoptosis. Our quantitative-binding data were in agreement with published cell-based assays. The regulation of p53 activity is in part determined through the specificity of its DNA-binding interactions.

Original languageEnglish (US)
Pages (from-to)589-596
Number of pages8
JournalJournal of Molecular Biology
Volume348
Issue number3
DOIs
StatePublished - May 6 2005
Externally publishedYes

Keywords

  • Apoptosis
  • DNA
  • Fluorescence anisotropy
  • Promoter
  • p53

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Molecular Biology

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