The process of protein prenylation involves the covalent linkage of either
farnesyl (15-carbon) or geranylgeranyl (20-carbon) isoprenoid lipds to conserved
cysteine residues in the carboxyl-terminus of proteins. Protein geranylgeranyltransferase
I (GGTase-I) is the enzyme that catalyzes the addition of the geranylgeranyl
moiety from geranylgeranyl pyrophosphate to the target protein, which contains a Cterminal
consensus sequence termed a CaaX motif. Geranylgeranylation is important to
the function of a number of proteins, including the majority of Rho GTPases, G protein
gamma subunits, and several other regulatory proteins. Studies over the past two
decades have revealed that many of these proteins contribute to tumor development
and metastasis. Blocking Rho GTPase activity through inhibition of GGTase-I in
particular has been advanced as a potential strategy for disease therapy. This review will provide an
overview of the CaaX prenyltransferases, the rationale for targeting GGTase-I in cancer in particular, and
the current status of GGTase-I inhibitor (GGTI) development.
Keywords: Prenylation, isoprenylation, isoprenoid, CaaX protein, GGTI, FTI, geranylgeranyl, farnesyl.
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