Y. Zhao et al., cDNA cloning, chromosome mapping and expression characterization of human geranylgeranyl pyrophosphate synthase, SCI CHINA C, 43(6), 2000, pp. 613-622
Geranylgeranyl pyrophosphate (GGPP) mainly participates in post-translation
al modification for various proteins including Rho/Rac, Rap and Rab familie
s, as well as in regulation for cell apoptosis. Geranylgeranyl pyrophosphat
e synthase (GGPPS), which catalyzes the condensation reaction between farne
syl diphosphate and isopentenyl diphosphate, is the key enzyme for synthesi
zing GGPP. We report the isolation of a gene transcript showing high homolo
gy with Drosophila GGPPS cDNA. The transcript is 1466 bp in length and cont
ains an intact open reading frame (ORF) ranging from nt 239 to 1138. This O
RF encodes a deduced protein of 300 residues with calculated molecular weig
ht of 35 ku, The deduced protein shows 57.5% identity and 75% similarity wi
th Drosophila GGPPS, and contains five characteristic domains of prenyltran
sferases. Northern hybridization revealed that human GGPPS was expressed hi
ghest in heart, and moderately in spleen, testis, brain, placenta, lung, li
ver, skeletal muscle, kidney and pancreas. No obvious bands were detected i
n other examined tissues. The GGPPS gene was located on human chromosome 1q
43 by Radiation Hybrid mapping method. It was proved that there was a putat
ive predisposing gene for prostate cancer in this region, and that analogs
of GGPP can inhibit the geranylgeranylation of p21rap protein in PC-3 prost
ate cancer cell lines. These facts suggest that GGPPS may be one of the can
didate genes for prostate cancer.