title: Quantitative determination of cellular farnesyltransferase activity: towards defining the minimum substrate reactivity for biologically relevant protein farnesylation.
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.
authors.affiliation: Syracuse University Department of Chemistry, 1-014 Center for Science and Technology, Syracuse, NY 13244-4100 (USA).
authors.forename: Susan C
authors.initials: SC
authors.lastname: Flynn
authors.forename: Danielle E
authors.initials: DE
authors.lastname: Lindgren
authors.forename: James L
authors.initials: JL
authors.lastname: Hougland
mesh_terms: D002478:Cells, Cultured; D004789:Enzyme Activation; D051231:Farnesyltranstransferase / Q000032:analysis* / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D017368:Protein Prenylation; D013379:Substrate Specificity
chemical_list: D051231:Farnesyltranstransferase
keywords: FTase; enzymes; post-translational modification; prenylation; protein modifications