J. Lipid Res.
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A more recent version of this article appeared on June 1, 2003

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J. Lipid Res., doi:10.1194/jlr.M300057-JLR200
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Submitted on February 3, 2003
Revised on March 19, 2003
Accepted on March 20, 2003

Monoterpene regulation of Ras and Ras-related protein expression

Sarah A. Holstein and Raymond J. Hohl

Internal Medicine and Pharmacology, University of Iowa, Iowa City, IA 52242

Corresponding Author: raymond-hohl{at}uiowa.edu

Monoterpenes, derived primarily from plants, are products of the isoprenoid biosynthetic pathway and function as chemical messengers with diverse functions. The biochemical bases for these activities are largely undefined. The Ras small GTPase superfamily of proteins consists of isoprenylated proteins that play key roles in signal transduction pathways known to regulate diverse cellular functions. In these studies we have examined the effects of monoterpenes on expression of Ras and Ras-related proteins, in the absence and presence of mevalonate depletion. Although prior studies have suggested that monoterpenes inhibit isoprenyl transferases, our studies clearly show that select monoterpenes inhibit upregulation of Ras and the Ras-related proteins. A structure-activity relationship model for these effects was defined. The ability of monoterpenes to regulate the expression of the Ras-related proteins was found to be independent of effects on cell proliferation or total cellular protein synthesis/degradation. We can conclude that monoterpenes selectively decrease levels of Ras and Ras-related proteins in a manner that is structure-dependent.


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