The Enzymology of CAAX Protein Prenylation

Many proteins involved in signal transduction and protein trafficking are posttranslationally modified by the covalent attachment of lipid groups. One form of lipid modification involves attachment of either a 15-carbon farnesyl or a 20-carbon geranylgeranyl isoprenoid lipid to a cysteine residue fourth from the C-terminus of the substrate protein. The attachment of the isoprenoid is the first step in a processing pathway that can include subsequent proteolysis of three carboxyl-terminal residues, methylation of the free carboxyl group of the resulting C-terminal prenylcysteine, and modification with additional lipid molecules. These modifications are necessary for targeting and attachment of these so-called CAAX proteins to the correct membrane as well as for the cellular function of the protein. The focus of this chapter is on the two protein prenyltransferases responsible for addition of the isoprenoid to the CAAX protein substrates. © 2011 Elsevier Inc.

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Author Patrick John Casey Pharmacology & Cancer Biology