cDNA cloning, chromosome mapping and expression characterization of human geranylgeranyl pyrophosphate synthase

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.