Wild-type p53 Activates Transcription in Vitro

Nature. 1992 Jul 2;358(6381):83-6. doi: 10.1038/358083a0.

Abstract

The p53 protein is an important determinant in human cancer and regulates the growth of cells in culture. It is known to be a sequence-specific DNA-binding protein with a powerful activation domain, but it has not been established whether it regulates transcription directly. Here we show that intact purified wild-type human and murine p53 proteins strongly activate transcription in vitro. This activation depends on the ability of p53 to bind to a template bearing a p53-binding sequence. By contrast, tumour-derived mutant p53 proteins cannot activate transcription from the template at all, and when complexed to wild-type p53, these mutants block transcriptional activation by the wild-type protein. Moreover, the simian virus 40 large T antigen inhibits wild-type p53 from activating transcription. Our results support a model in which p53 directly activates transcription but this activity can be inhibited by mutant p53 and SV40 large T antigen through interaction with wild-type p53.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Polyomavirus Transforming / metabolism
  • DNA Mutational Analysis
  • DNA-Binding Proteins / physiology
  • Gene Expression Regulation
  • HeLa Cells
  • Humans
  • In Vitro Techniques
  • Mice
  • Neoplasm Proteins / metabolism
  • Promoter Regions, Genetic
  • Structure-Activity Relationship
  • Transcription Factors / physiology*
  • Transcription, Genetic*
  • Tumor Suppressor Protein p53 / chemistry
  • Tumor Suppressor Protein p53 / physiology*

Substances

  • Antigens, Polyomavirus Transforming
  • DNA-Binding Proteins
  • Neoplasm Proteins
  • Transcription Factors
  • Tumor Suppressor Protein p53