Quantitative determination of cellular farnesyltransferase activity: towards defining the minimum substrate reactivity for biologically relevant protein farnesylation

Susan C. Flynn, Danielle E. Lindgren, James L Hougland

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Prenylation is a post-translational modification wherein an isoprenoid group is attached to a protein substrate by a protein prenyltransferase. Hundreds of peptide sequences are in vitro substrates for protein farnesyltransferase (FTase), but it remains unknown which of these sequences can successfully compete for in vivo prenylation. Translating in vitro studies to predict in vivo protein farnesylation requires determining the minimum reactivity needed for modification by FTase within the cell. Towards this goal, we developed a reporter protein series spanning several orders of magnitude in FTase reactivity as a calibrated sensor for endogenous FTase activity. Our approach provides a minimally invasive method to monitor changes in cellular FTase activity in response to environmental or genetic factors. Determining the reactivity "threshold" for in vivo prenylation will help define the prenylated proteome and identify prenylation-dependent pathways for therapeutic targeting.

Original languageEnglish (US)
Pages (from-to)2205-2210
Number of pages6
JournalChembiochem : a European journal of chemical biology
Volume15
Issue number15
DOIs
StatePublished - Oct 13 2014

Keywords

  • enzymes
  • FTase
  • post-translational modification
  • prenylation
  • protein modifications

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry

Fingerprint Dive into the research topics of 'Quantitative determination of cellular farnesyltransferase activity: towards defining the minimum substrate reactivity for biologically relevant protein farnesylation'. Together they form a unique fingerprint.

  • Cite this