Incorporation of Radiolabeled Prenyl Alcohols and Their Analogs into Mammalian Cell Proteins

Prenylated proteins comprise a diverse family of proteins that are posttrans-lationally modified by either a farnesyl group or one or more geranylgeranyl groups (1–3). Recent studies suggest that members of this family are involved in a number of cellular processes, including cell signaling (4–6), differentiation (7–9), proliferation (10–12), cytoskeletal dynamics (13–15), and endocytic and exocytic transport (4,16,17). The authors’ studies have focused on the role of prenylated proteins in the cell cycle (18). Exposure of cultured cells to competitive inhibitors (statins) of 3-hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) reductase not only blocks the biosynthesis of mevalonic acid (MVA), the biosynthetic precursor of both farnesyl and geranylgeranyl groups, but pleio-tropically inhibits DNA replication and cell-cycle progression (10,18–20). Both phenomena can be prevented by the addition of exogenous MVA (10,18,19). The authors have observed that all- trans -geranylgeraniol (GGOH) and, in a few cases, all- trans -farnesol (FOH) can prevent the statin-induced inhibition of DNA synthesis (21). In an effort to understand the biochemical basis of these effects, the authors have developed methods for the labeling and two-dimensional gel analysis of prenylated proteins that should be widely applicable. These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.