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lüll Chemistry and biology of Ras farnesyltransferase Cho KN; Lee KIArch Pharm Res 2002[Dec]; 25 (6): 759-69Mutated forms of ras are found in many human tumors and the rate of incidence is significantly higher in colon and pancreatic cancers. The protein product from the ras oncogene is a small G-protein, p21(ras) (Ras) that is known to play a key role in the signal transduction cascade and cell differentiation and proliferation. Mutated Ras is unable to regulate itself and remains constantly activated, leading to uncontrolled cell growth. The function of Ras in signal transduction requires its location near the growth factor receptor at the cell membrane. However, Ras does not have a transmembrane domain. Ras requires farnesylation to increase its hydrophobicity and subsequent plasma membrane association for its transforming activity. This key post-translational modification is catalyzed by the enzyme Ras famesyltransferase (FTase), which transfers a famesyl group from farnesylpyrophosphate to the C-terminal cysteine of the Ras protein. The requirement has focused attention on FTase as a target for therapeutic intervention. Selective inhibition of FTase will prevent Ras protein from association with the plasma membrane, leading to a disruption of oncogenic Ras function.|*Genes, ras[MESH]|Alkyl and Aryl Transferases/antagonists & inhibitors/*chemistry/*physiology[MESH]|Animals[MESH]|Cell Transformation, Neoplastic/genetics/metabolism[MESH]|Humans[MESH]|Signal Transduction/genetics/physiology[MESH] |