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Prenylation of RAS and Inhibitors of Prenyltransferases

  • Chapter
Regulation of the RAS Signaling Network

Abstract

The recent development of farnesyltransferase inhibitors which inhibit the growth of RAS-transformed cells demonstrates that membrane association of RAS and other monomeric G proteins such as Rho is important for the tumorigenicity of RAS.1–3 In the early 1980s, it was established that RAS is C-terminally modified and that this modification is important for both its membrane association and tumorigenicity. This observation was followed by the elucidation of the steps involved in the C-terminal modification. The first step in this modification is the addition of a farnesyl group to RAS utilizing farnesyl pyrophosphate (FPP) as the prenyl donor. Characterization of the farnesylation led to the identification of the enzyme farnesyltransferase (FTase). This enzyme and two related enzymes, geranylgeranyltransferases (GGTases) I and II, form a family of enzymes called protein prenyl-transferases. The structure and function of these enzymes are being elucidated, which could provide vital information concerning the active sites of the enzyme. Inhibitors of these enzymes have been identified by a variety of approaches, and the inhibitors have been utilized to inhibit the growth of RAS tumors. In this chapter we will focus on two topics: (i) the structure and function of protein prenyltransferases and (ii) inhibitors of prenyltransferases.

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  1. Isabel Sattler
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  2. Fuyuhiko Tamanoi
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© 1996 R.G. Landes Company

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Sattler, I., Tamanoi, F. (1996). Prenylation of RAS and Inhibitors of Prenyltransferases. In: Regulation of the RAS Signaling Network. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-1183-6_4

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  • DOI: https://doi.org/10.1007/978-1-4613-1183-6_4

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4612-8502-1

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