Abstract
Geranylgeranyl pyrophosphate (GGPP) mainly participates in post-translational modification for various proteins including Rho/Rac, Rap and Rab families, as well as in regulation for cell apoptosis. Geranylgeranyl pyrophosphate synthase (GGPPS), which catalyzes the condensation reaction between farnesyl diphosphate and isopentenyl diphosphate, is the key enzyme for synthesizing GGPP. We report the isolation of a gene transcript showing high homology withDrosophila GGPPS cDNA. The transcript is 1 466 bp in length and contains an intact open reading frame (ORF) ranging from nt 239 to 1 138. This ORF encodes a deduced protein of 300 residues with calculated molecular weight of 35 ku. The deduced protein shows 57.5% identity and 75% similarity withDrosophila GGPPS, and contains five characteristic domains of prenyltransferases. Northern hybridization revealed that humanGGPPS was expressed highest in heart, and moderately in spleen, testis, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. No obvious bands were detected in other examined tissues. TheGGPPS gene was located on human chromosome 1q43 by Radiation Hybrid mapping method. It was proved that there was a putative predisposing gene for prostate cancer in this region, and that analogs of GGPP can inhibit the geranylgeranylation of p21rap protein in PC-3 prostate cancer cell lines. These facts suggest thatGGPPS may be one of the candidate genes for prostate cancer.
Similar content being viewed by others
References
Bogusko, M. S., McCormick, F., Proteins regulating Ras and its relatives, Nature, 1993, 366(16): 643.
Clark, S., Protein isoprenylation and methylation at carboxy-terminal cysteine residues, Annu. Rev. Biochem., 1992, 61: 355.
Marshall, C. J., Protein prenylation: a mediator of protein-protein interactions, Science, 1993, 259: 1865.
Macchia, M., Jannitti, N., Gervasi, G. et al., Geranylgeranyl diphosphate-based inhibitors of post-translational geranylgeranylation of cellular proteins, J. Med. Chem., 1996, 39(7): 1352.
Gesi, M., Pellegrini, A., Soldani, P. et al., Ultrastructural and biochemical evidence of apoptosis induced by a novel inhibitor of protein geranylgeranylation in human MIA PaCa-2 pancreatic cancer cells, Ultrastructure Pathol., 1998, 22(3): 253.
Sagami, H., Korenaga, T., Ogura, K. et al., Studies on geranylgeranyl diphosphate synthase from rat liver: specific inhibition by 3-azageranylgeranyl diphosphate, Arch. Biochem. Biophys., 1992, 297(2): 314.
Sagami, H., Ishi, K., Ogura, K., Occurrence and unusual properties of geranylgeranyl pyrophosphate synthetase of pig liver, Biochem. Int., 1981, 3: 669.
Sagami, H., Korenaga, T., Ogura, K., Geranylgeranyl diphosphate synthase catalyzing the single condensation between isopentenyl diphosphate and farnesyl diphosphate, J. Biochem., 1993, 114: 118.
Lai, C., McMahon, R., Young, C. et al., quemao, a Drosophila bristle locus, encodes geranylgeranyl pyrophosphate synthase, Gentics, 1998, 149: 1051.
Ashby, M. N., Edwards, P. A., Elucidation of the deficiency in two yeast coenzyme Q mutants: characterization of the structural gene encoding hexaprenyl pyrophosphate synthetase, J. Biol. Chem., 1990, 265: 13157.
Tarshis, L. C., Yan, M., Poulter, C. D. et al., Crystal structure of recombinant farnesyl diphosphate synthase at 2.6-A resolution, Biochemistry, 1994, 33: 10871.
Quondam, M., Barbato, C., Pickford, A. et al., Homology modeling of Neurospora crassa geranylgeranyl pyrophosphate synthaseL: structural interpretation of mutant phenotype, Protein Eng., 1997, 10(9): 1047.
Chen, A., Poulter, C. D., Isolation and characterization of idaA: the gene for short chain isoprenyl diphosphate synthase fromMethanobacterium thermoautorophicum, Arch. Biochem. Biophys., 1994, 314: 399.
Rogers, S., Wells, R., Rechsteiner, M., Amino acid sequences common to rapidly degraded proteins: the PEST hypothesis, Science, 1986, 234(17): 364.
Rechsteiner, M., Rogers, S., Rote, K., Protein structure and intracellular stability, Trends in Biochem. Sci., 1987, 12: 390.
Guijarro, C., Blanco-Colio, L. M., Ortego, M. et al., 3-Hydroxy-3-methylglutaryl coenzyme a reductase and isoprenylation inhibitors induce apoptosis of vascular smooth muscle cells kin culture, Circ. Res., 1998, 83(5): 490.
Berthon, P., Valeri, A., Cohen-Akenine, A. et al., Predisposing gene for early-onset prostate cancer, localized on chromosome 1q42.2-43, Am. J. Hum. Genet., 1998, 62: 1416.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Zhao, Y., Yu, L., Gao, J. et al. cDNA cloning, chromosome mapping and expression characterization of human geranylgeranyl pyrophosphate synthase. Sci. China Ser. C.-Life Sci. 43, 613–622 (2000). https://doi.org/10.1007/BF02882282
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02882282