James Michael Wardleworth

Farnesyl transferase inhibitors

Ras proteins belong to the small guanine triphosphatebinding protein (G protein) superfamily that is widely distributed in mammalian cells (1–3). The G protein superfamily consists of more than 100 members that are structurally classified into at least five families, including the Ras, Rho, Rab, Sarl/Arf, and Ran families. They all have consensus amino acid sequences for specific binding with guanosine diphosphate (GDP) and guanosine triphosphate (GTP), for GTPase activity (which hydrolyzes bound GTP to GDP and Pi) and for downstream effectors. G proteins regulate a wide variety of cellular functions, including gene expression in normal cell growth and differentiation (Ras), cytoskeletal reorganization and gene expression (Rho), vesicle trafficking (Rab and Sarl/Arf), nucleocytoplasmic transport (Ran), and microtubule organization (Ran). They are structurally similar and are physiologically regulated by many of the same signals. Multiple upstream regulators and downstream effectors have been identified, and their modes of activation and crosstalk have been extensively studied (4, 5).