Prenyl-binding domains: potential targets for Ras inhibitors and anti-cancer drugs.
Ras and Rho GTPases are prominent participants in malignant transformation. They possess an essential prenyl group (farnesyl or geranylgeranyl) that endows them with membrane-tethering ability and functional specificity. Accumulating evidence suggests that prenyl groups are involved primarily in lipid-protein interactions, and recent experiments point to prenyl-binding hydrophobic pockets in proteins regulating Ras and Rho in normal cells and cancer cells. This review presents the evidence for such prenyl-binding domains as significant players in the control of Ras-like GTPases, and the emerging concept of prenyl-binding domains as potential targets for Ras inhibitors and anti-cancer drugs.
Kloog
Yoel
Y
Department of Neurobiochemistry, The George S. Wise Faculty of Life Sciences, Tel-Aviv University, 69978 Tel-Aviv, Israel. yoelk@taunex.tau.ac.il
Cox
Adrienne D
AD
D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D009369:Neoplasms / Q000628:therapy*; D017368:Protein Prenylation; D018631:ras Proteins / Q000037:antagonists & inhibitors*
D018631:ras Proteins