Protein prenylation is a post-translational modification that is responsible for membrane association and protein-protein interactions. Because the oncogenic protein Ras is farnesylated, several farnesyltransferase inhibitors (FTIs) have been developed for anti-cancer activity. Many FTIs in clinical trials have demonstrated anti-tumor activity on non-Ras dependent cancers, by an unknown mechanism. We developed a method allowing for quantification of the prenylome using microscopy and flow cytometry. We show that metabolically incorporating alkyne isoprenoids in mammalian cells, followed by a 'click' reaction to a fluorophore, allows for detection of prenylated proteins. Addition of inhibitors of the prenyltransferases dynamically changes the levels of prenylated proteins in a cell specific manner. Furthermore, we demonstrate that the levels of prenylated proteins are increased in a cellular model of aging, indicating a potential involvement of protein prenylation in aging diseases. These results highlight the applicability of prenylome labeling for further studies on the intracellular targets of FTIs.

Imaging and quantification of prenylated proteins in cells reveals elevated levels of prenylated proteins in a cell aging model

243rd National Meeting (2012)

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