Protein Geranylgeranyltransferase Type 1 as a Target in Cancer.
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.
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Related Subject Headings
- Protein Prenylation
- Oncology & Carcinogenesis
- Neoplasms
- Humans
- Farnesyltranstransferase
- Enzyme Inhibitors
- Animals
- Alkyl and Aryl Transferases
- 3404 Medicinal and biomolecular chemistry
- 3211 Oncology and carcinogenesis
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Protein Prenylation
- Oncology & Carcinogenesis
- Neoplasms
- Humans
- Farnesyltranstransferase
- Enzyme Inhibitors
- Animals
- Alkyl and Aryl Transferases
- 3404 Medicinal and biomolecular chemistry
- 3211 Oncology and carcinogenesis