Cotranslation of activated mutant p53 with wild type drives the wild-type p53 protein into the mutant conformation

Cell. 1991 May 31;65(5):765-74. doi: 10.1016/0092-8674(91)90384-b.

Abstract

Activating mutations of p53 promote tumor progression. The mutant protein adopts a characteristic conformation, which lacks the growth suppressor function of wild-type p53. We show that mutant p53 can drive cotranslated wild-type p53 into the mutant conformation: a similar effect in vivo would block wild-type suppressor function with dominant negative effect. The cotranslational effect of mutant p53 on wild-type conformation depends upon interaction between nascent polypeptides and oligomerization of the full-length proteins. We also show that oligomers of p53 proteins can be induced to change conformation in a cooperative manner. Cell growth stimulation induces a similar conformational change in p53, and our present results indicate that this may involve allosteric regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Division
  • Cloning, Molecular
  • Codon
  • Genes, Tumor Suppressor*
  • Humans
  • Mice
  • Mutagenesis, Site-Directed*
  • Plasmids
  • Protein Biosynthesis*
  • Protein Conformation
  • Thermodynamics
  • Transcription, Genetic
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • Codon
  • Tumor Suppressor Protein p53