Isolation and sequence of the human farnesyl pyrophosphate synthetase cDNA. Coordinate regulation of the mRNAs for farnesyl pyrophosphate synthetase, 3-hydroxy-3-methylglutaryl coenzyme A reductase, and 3-hydroxy-3-methylglutaryl coenzyme A synthase by phorbol ester.

摘要: We report the isolation and nucleotide sequence of human farnesyl pyrophosphate synthetase cDNA, an enzyme in cholesterogenic pathway. Partial cDNAs for were isolated by screening hepatoma (HepG2) placental cDNA libraries with rat liver as a probe. Anchored polymerase chain reaction was used to isolate 5'-end cDNA. The has high identity (86%) Treatment monocytic leukemia cell line THP-1 phorbol esters led 2--7-fold increases mRNA concentrations three enzymes, synthetase, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, HMG-CoA synthase within 5 h. Immunoprecipitation radiolabeled cells demonstrated that there corresponding increase rate synthesis all proteins. addition cycloheximide also enzymes. resulted superinduction mRNAs; levels increased 35-fold, 17-fold, reductase 16-fold h after treatment. returned pretreatment 20 Cells preincubated presence lipoprotein-deficient fraction serum plus mevinolin induce mRNAs. Addition these derepressed further These results are consistent hypothesis contain short-lived negative transcription factor which regulates FPP genes. Phorbol regulate same genes, presumably modifying common and/or inducing positive factor(s).