Biochemical and Biological Analyses of Farnesyl-Protein Transferase Inhibitors

  • Nancy E. Kohl
  • Kenneth S. Koblan
  • Charles A. Omer
  • Allen Oliff
  • Jackson B. Gibbs
Part of the Methods In Molecular Biology™ book series (MIMB, volume 84)


Farnesyl-protein transferase (FPTase) catalyzes the postiranslational addition of the IScarbon isoprenoid, farnesyl, to approx 20 cellular proteins. Farnesylation is essential for the membrane localization and function of the modified proteins. Among these proteins are the products of the ras oncogenes, Harvey (Ha), Kirsten (Ki), and N-Ras. Ras is synthesized in the cytoplasm as a biologically inactive precursor that localizes to the plasma membrane and attains cell-transforming activity upon famesylation (1, 2, 3, 4). FPTase has therefore become a target for the development of inhibitors of Ras function, which will be effective against human tumors (5, 6, 7), particularly leukemias and pancreatic and colon carcinomas where oncogenically mutated ras genes are frequently found (8). Here, we describe a series of in vitro, cell-based, and in vivo assays that permit the identification and characterization of inhibitors of FPTase.


Mouse Mammary Tumor Virus Geranylgeranyl Pyrophosphate Rodent Fibroblast Tissue Culture Cluster FPTase Inhibitor 
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.


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Copyright information

© Humana Press Inc. 1998

Authors and Affiliations

  • Nancy E. Kohl
    • 1
  • Kenneth S. Koblan
    • 1
  • Charles A. Omer
    • 1
  • Allen Oliff
    • 1
  • Jackson B. Gibbs
    • 1
  1. 1.Department of Cancer ResearchMerck Research LaboratoriesWest Point

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