Farnesol is utilized for protein isoprenylation and the biosynthesis of cholesterol in mammalian cells

Dean C. Crick, Douglas A. Andres, Charles J. Waechter

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65 Scopus citations


Evidence has been obtained indicating that free farnesol (F-OH) can be utilized for isoprenoid biosynthesis in mammalian cells. When rat C6 glial cells and an African green monkey kidney cell line (CV-1) were incubated with [3H]F-OH, radioactivity was incorporated into cholesterol, ubiquinone (CoQ) and isoprenylated proteins. The incorporation of label from [3H]F-OH into cholesterol in C6 and CV-1 cells was blocked by squalestatin 1 (SQ) which specifically inhibits the conversion of farnesyl pyrophosphate (F-P-P) to squalene. This result strongly suggests that cholesterol, and probably CoQ and protein, is metabolically labeled via F-P-P. SDS-PAGE analysis of the delipidated protein fractions from C6 and CV-1 cells revealed several labeled polypeptides. Consistent with these proteins being modified by isoprenylation of cysteine residues, Pronase E digestion released a major labeled product with the chromatographic mobility of [3H]farnesyl-cysteine (F-Cys). A different set of polypeptides was labeled when C6 and CV-1 cells were incubated with [3H]geranylgeraniol (GG-OH). Both sets of proteins appear to be metabolically labeled by [3H]mevalonolactone, and [3H]-labeled F-Cys and geranylgeranyl-cysteine (GG-Cys) were liberated from these proteins by Pronase E treatment. These cellular and biochemical studies indicate that F-OH can be used for isoprenoid biosynthesis and protein isoprenylation in mammalian cells after being converted to F-P-P by phosphorylation reactions that remain to be elucidated.

Original languageEnglish
Pages (from-to)590-599
Number of pages10
JournalBiochemical and Biophysical Research Communications
Issue number2
StatePublished - 1995

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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