Prenylation of CaaX-type proteins: Basic principles through clinical applications

Published

Journal Article (Review)

Post-translational modification by attachment of lipid moieties is critical for the biological activity of many membrane-associated proteins. This process, termed lipidation, serves to direct and anchor specific proteins to the cell membrane and can also play a role in important protein-protein interactions. A wide variety of lipids can be attached to proteins, including saturated acyl groups such as myristoyl and palmitoyl chains, glycosylphosphatidylinositol (GPI) moieties, and the 15- and 20-carbon isoprenoid groups famesyl and geranylgeranyl, respectively. Some lipidated proteins have only a single modification, whereas many others may have multiple, in some cases variable, modifications, in which each permuation confers a unique chemical property and distinct functional characteristic to the parent protein. This chapter deals primarily with the biochemistry and biology of protein prenylation, focusing on those proteins that contain a so-called CaaX motif at their C-terminus. The C-terminal processing of CaaX proteins is initiated by addition of either a farnesyl or geranylgeranyl isoprenoid to the conserved cysteine of the CaaX motif. Farnesylation of Ras proteins in particular has attracted a great deal of attention and is the primary reason why the enzyme responsible, termed protein farnesyltransferase (FTase), has been targeted for development of inhibitors that are currently being evaluated in clinical trials as anticancer agents. © 2002.

Duke Authors

Cited Authors

  • Hurwitz, HI; Casey, PJ

Published Date

  • December 1, 2002

Published In

Volume / Issue

  • 52 /

Start / End Page

  • 531 - 550

International Standard Serial Number (ISSN)

  • 1063-5823

Citation Source

  • Scopus