Covalent modification by isoprenoid lipids (prenylation) is now recognized as a mechanism to promote membrane interactions and biological activities of a variety of cellular proteins. Both the 15-carbon farnesyl and 20-carbon geranylgeranyl isoprenoids are involved in these modifications, which occur on carboxyl-terminal cysteine residues of proteins (Fig. 1). Known prenylated proteins include ...

1,4-Dihydroxy-2-naphthoate [1, 21 as the crucial intermediate in the biosynthesis of menaquinones in bacteria is formed from shikimate [3] via chorismate [2] and o-succinylbenzoate [I]. Prenylation [4] and methylation [I] result in formation of menaquinones of different length of side chain. The principal steps of the synthesis of the naphthoquinone moiety are similar for both plants and bacter...

Protein isoprenylation is a lipid posttranslational modification required for the function of many proteins that share a carboxyl-terminal CAAX motif. The X residue determines which isoprenoid will be added to the cysteine. When X is a methionine or serine, the farnesyl-transferase transfers a farnesyl, and when X is a leucine or isoleucine, the geranygeranyl-transferase I, a geranylgeranyl gro...

Members of the Ras and Rho families of small GTPases regulate diverse signaling pathways that promote normal physiological processes as well as diseases such as cancer. The localization of small GTPases in distinct subcellular regions defines which signaling pathways they activate, thus defining their participation in disease. The plasma membrane is viewed as the region of highest activity for ...

Hepatitis delta antigen (HDAg) consists of two species, large (LHDAg) and small (SHDAg), which are identical in sequence except that the large form contains 19 extra amino acids at the C terminus. The large form is prenylated on the Cxxx motif. The small form can trans activate HDV RNA replication, while the large form inhibits it. To determine the molecular basis for their differential functio...

Recent evidence suggests that apoptosis may be involved in the control of vascular smooth muscle cell (VSMC) number in atherosclerotic lesions. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have been reported to induce apoptosis in a variety of tumor cell lines. To evaluate whether these agents also induce apoptosis of VSMCs, cultured rat VSMCs were treated with increasin...

Lonafarnib (SCH66336) is a farnesyl transferase inhibitor (FTI) that inhibits the post-translational lipid modification of H-Ras and other farnesylated proteins. K- and N-Ras are also substrates of farnesyl transferase; however, upon treatment with FTIs, they are alternatively prenylated by geranylgeranyl transferase-1. Despite the failure to abrogate prenylation of K- and N-Ras, growth of many...