Wild-type p53 mediates positive regulation of gene expression through a specific DNA sequence element

Genes Dev. 1992 Jul;6(7):1143-52. doi: 10.1101/gad.6.7.1143.

Abstract

It has been reported recently that the wild-type p53 gene product can positively regulate the expression of a test gene adjacent to the enhancer-promoter elements of the murine muscle-specific creatine kinase (MCK) gene. This discussion reports the identification of a wild-type p53 protein-specific DNA-binding element located within the p53-responsive region of the MCK enhancer-promoter element. This p53 protein/DNA-binding element has been defined by DNase I footprint analysis, which identified a 50-bp region. This 50-bp sequence was sufficient to confer wild-type p53 responsiveness on a heterologous minimal promoter. The mutant forms of p53 protein are much less capable of stimulating this DNA element. This study has identified the first example of a naturally occurring wild-type p53-specific DNA-binding element that is able to mediate positive regulation of a test gene. The results suggest a biological function in gene regulation for the wild-type p53 protein that is lost or altered in the mutant p53 proteins.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • Cell Line
  • Creatine Kinase / genetics*
  • Creatine Kinase / metabolism
  • DNA / metabolism
  • Gene Expression Regulation, Enzymologic*
  • Humans
  • Molecular Sequence Data
  • Muscles / enzymology
  • Mutation
  • Promoter Regions, Genetic
  • Regulatory Sequences, Nucleic Acid*
  • Temperature
  • Transcriptional Activation
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Tumor Suppressor Protein p53
  • DNA
  • Creatine Kinase

Associated data

  • GENBANK/M79310
  • GENBANK/M81118
  • GENBANK/S39469
  • GENBANK/S49473
  • GENBANK/S49475
  • GENBANK/X65112
  • GENBANK/X65113
  • GENBANK/X66096
  • GENBANK/X66097
  • GENBANK/X66098