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ras Oncogene Inhibitors

  • Nancy E. Kohl
Chapter
Part of the Cancer Drug Discovery and Development book series (CDD&D)

Abstract

The mammalian ras genes, N-, Ha- and Ki-ras, encode four highly homologous 21-Kd proteins— N-and Ha-Ras, and the splice variants Ki4A- and Ki4B-Ras that function as molecular switches in the regulation of cell proliferation, survival, and differentiation. Situated at the inner surface of the plasma membrane, these proteins transmit extracellular signals from membrane-localized receptor tyrosine kinases to the nucleus. Typical of guanosine 5’ triphosphate (GTP)-binding proteins, Ras cycles between the active, GTP-bound and inactive, guanosine 5’ diphosphate (GDP)-bound states through the action of its intrinsic GTPase activity, together with the action of guanine nucleotide exchange factors and GTPase-activating proteins (GAPs). Constitutively activated forms of Ras with compromised GTPase activity that are capable of deregulated cell growth are encoded by ras genes with point mutations in codons 12, 13, or 61 (1). Activation of Ras by mutation is a frequent finding in human tumors, with an overall incidence of 30%.

Keywords

Human Tumor Cell Line Advanced Solid Tumor Farnesyltransferase Inhibitor Farnesyl Transferase Inhibitor Protein Transferase 
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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© Springer Science+Business Media New York 2004

Authors and Affiliations

  • Nancy E. Kohl

There are no affiliations available

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