Inhibition of an activated Ras protein with genetically selected peptide aptamers

Stephen E. Kurtz, Kim Esposito, Weimin Tang, Rolf Menzel

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Mutant alleles of Ras maintain an activated, GTP-bound conformation and relay mitogenic signals that cannot be turned off. A genetic selection in Saccharomyces cerevisiae was used to identify peptide aptamers that suppress the growth arrest phenotype of an activated Ras allele. Peptide aptamers were expressed as C-terminal fusions to glutathione-S-transferase. Modifications that alter the coding capacity of the peptide aptamer indicate it is necessary for Ras2-Val19 suppression. Aptamer expression also reduces the elevated levels of cAMP and suppresses the heat shock sensitivity characteristic of Ras-activated yeast cells. The peptide aptamer retains suppressor activity when fused to thioredoxin. The peptide aptamer expression strategy described here indicates that aptamers presented as unconstrained peptides have functional capacity in vivo.

Original languageEnglish (US)
Pages (from-to)38-46
Number of pages9
JournalBiotechnology and Bioengineering
Volume82
Issue number1
DOIs
StatePublished - Apr 5 2003

Keywords

  • Genetic suppressor
  • Peptide aptamer library
  • Ras
  • Saccharomyces cerevisiae

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

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