Human geranylgeranyl diphosphate synthase: isolation of the cDNA, chromosomal mapping and tissue expression

We report the nucleotide sequence of human geranylgeranyl diphosphate (GGPP) synthase cDNA isolated from a fetal heart library. The 2.5 kb cDNA encodes a protein of 34 kDa. The protein contains six domains that have been identified previously in many other prenyltransferases. Recombinant, purified h...

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Main Authors: Johan Ericsson, John M. Greene, Kenneth C. Carter, Brenda K. Shell, D. Roxanne Duan, Charles Florence, Peter A. Edwards
Format: Article
Language:English
Published: Elsevier 1998-09-01
Series:Journal of Lipid Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0022227520321593
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author Johan Ericsson
John M. Greene
Kenneth C. Carter
Brenda K. Shell
D. Roxanne Duan
Charles Florence
Peter A. Edwards
author_facet Johan Ericsson
John M. Greene
Kenneth C. Carter
Brenda K. Shell
D. Roxanne Duan
Charles Florence
Peter A. Edwards
author_sort Johan Ericsson
collection DOAJ
description We report the nucleotide sequence of human geranylgeranyl diphosphate (GGPP) synthase cDNA isolated from a fetal heart library. The 2.5 kb cDNA encodes a protein of 34 kDa. The protein contains six domains that have been identified previously in many other prenyltransferases. Recombinant, purified histidine-tagged protein exhibited the enzymatic properties associated with GGPP synthase, namely the synthesis of GGPP from farnesyl diphosphate and isopentenyl diphosphate. Transient transfection of mammalian cells with a plasmid encoding the putative GGPP synthase resulted in a 55-fold increase in GGPP synthase activity. Taken together, these results establish that the cDNA encodes the mammalian GGPP synthase protein. The mRNA for GGPP synthase was expressed ubiquitiously. Of the 16 human tissues examined, the highest expression of the mRNA was in testis. The mRNA levels in cultured HeLa cells were unaffected by alterations in cellular sterol levels and contrasted with the significant regulation of isopentenyl diphosphate synthase mRNA under these same conditions. Fluorescent in situ hybridization was used to map the single gene encoding human GGPP synthase to chromosome 1q43.—Ericsson, J., J. M. Greene, K. C. Carter, B. K. Shell, D. R. Duan, C. Florence, and P. A. Edwards. Human geranylgeranyl diphosphate synthase: isolation of the cDNA, chromosomal mapping, and tissue expression.
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spelling doaj.art-d2311d0917744433a4eae5e16c96697a2022-12-21T19:41:16ZengElsevierJournal of Lipid Research0022-22751998-09-0139917311739Human geranylgeranyl diphosphate synthase: isolation of the cDNA, chromosomal mapping and tissue expressionJohan Ericsson0John M. Greene1Kenneth C. Carter2Brenda K. Shell3D. Roxanne Duan4Charles Florence5Peter A. Edwards6Departments of Biological Chemistry, University of California Los Angeles, Los Angeles, CA 90095; Medicine, University of California Los Angeles, Los Angeles, CA 90095Human Genome Sciences, Bioinformatics, 9410 Key West Avenue, Rockville, MD 20850Human Genome Sciences, Bioinformatics, 9410 Key West Avenue, Rockville, MD 20850Human Genome Sciences, Bioinformatics, 9410 Key West Avenue, Rockville, MD 20850Human Genome Sciences, Bioinformatics, 9410 Key West Avenue, Rockville, MD 20850Human Genome Sciences, Bioinformatics, 9410 Key West Avenue, Rockville, MD 20850To whom correspondence should be addressed.; Departments of Biological Chemistry, University of California Los Angeles, Los Angeles, CA 90095; Medicine, University of California Los Angeles, Los Angeles, CA 90095; the Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA 90095We report the nucleotide sequence of human geranylgeranyl diphosphate (GGPP) synthase cDNA isolated from a fetal heart library. The 2.5 kb cDNA encodes a protein of 34 kDa. The protein contains six domains that have been identified previously in many other prenyltransferases. Recombinant, purified histidine-tagged protein exhibited the enzymatic properties associated with GGPP synthase, namely the synthesis of GGPP from farnesyl diphosphate and isopentenyl diphosphate. Transient transfection of mammalian cells with a plasmid encoding the putative GGPP synthase resulted in a 55-fold increase in GGPP synthase activity. Taken together, these results establish that the cDNA encodes the mammalian GGPP synthase protein. The mRNA for GGPP synthase was expressed ubiquitiously. Of the 16 human tissues examined, the highest expression of the mRNA was in testis. The mRNA levels in cultured HeLa cells were unaffected by alterations in cellular sterol levels and contrasted with the significant regulation of isopentenyl diphosphate synthase mRNA under these same conditions. Fluorescent in situ hybridization was used to map the single gene encoding human GGPP synthase to chromosome 1q43.—Ericsson, J., J. M. Greene, K. C. Carter, B. K. Shell, D. R. Duan, C. Florence, and P. A. Edwards. Human geranylgeranyl diphosphate synthase: isolation of the cDNA, chromosomal mapping, and tissue expression.http://www.sciencedirect.com/science/article/pii/S0022227520321593prenyltransferase
spellingShingle Johan Ericsson
John M. Greene
Kenneth C. Carter
Brenda K. Shell
D. Roxanne Duan
Charles Florence
Peter A. Edwards
Human geranylgeranyl diphosphate synthase: isolation of the cDNA, chromosomal mapping and tissue expression
Journal of Lipid Research
prenyltransferase
title Human geranylgeranyl diphosphate synthase: isolation of the cDNA, chromosomal mapping and tissue expression
title_full Human geranylgeranyl diphosphate synthase: isolation of the cDNA, chromosomal mapping and tissue expression
title_fullStr Human geranylgeranyl diphosphate synthase: isolation of the cDNA, chromosomal mapping and tissue expression
title_full_unstemmed Human geranylgeranyl diphosphate synthase: isolation of the cDNA, chromosomal mapping and tissue expression
title_short Human geranylgeranyl diphosphate synthase: isolation of the cDNA, chromosomal mapping and tissue expression
title_sort human geranylgeranyl diphosphate synthase isolation of the cdna chromosomal mapping and tissue expression
topic prenyltransferase
url http://www.sciencedirect.com/science/article/pii/S0022227520321593
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