Structure of the mitogen-inducible TIS10 gene and demonstration that the TIS10-encoded protein is a functional prostaglandin G/H synthase
The TIS10 cDNA was cloned as a primary response gene transcript whose mRNA rapidly accumulates in 3T3 cells treated with serum, polypeptide growth factors, or phorbol esters. The sequence of the TIS10 cDNA suggested that the gene encodes a protein with strong similarities to prostaglandin G/H syntha...
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Published in | The Journal of biological chemistry Vol. 267; no. 7; pp. 4338 - 4344 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Bethesda, MD
American Society for Biochemistry and Molecular Biology
05.03.1992
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Subjects | |
Online Access | Get full text |
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Summary: | The TIS10 cDNA was cloned as a primary response gene transcript whose mRNA rapidly accumulates in 3T3 cells treated with serum,
polypeptide growth factors, or phorbol esters. The sequence of the TIS10 cDNA suggested that the gene encodes a protein with
strong similarities to prostaglandin G/H synthase/cyclooxygenase (EC 1.14.99.1). Transient transfection into COS-1 cells of
an expression vector driving the TIS10 cDNA leads to production and secretion of prostaglandin E2. Microsomes prepared from
COS-1 cells transfected with this construct demonstrate both hydroperoxidase and cyclooxygenase activities similar to that
demonstrated by cells transfected with a vector encoding the ovine prostaglandin G/H synthase. These data demonstrate that
the TIS10 gene encodes a functional prostaglandin synthase/cyclooxygenase distinct from the prostaglandin synthase/cyclooxygenase
whose cDNAs and/or genes have previously been cloned from sheep, mouse, and man. The structure of the TIS10 gene, determined
by a combination of sequencing of genomic clones and polymerase chain reactions from genomic clones, demonstrates remarkable
exon-intron conservation with the human prostaglandin synthase/cyclooxygenase gene. A 1-kilobase sequence located immediately
proximal to the start site of transcription of the TIS10 gene can confer phorbol ester and serum inducibility to a luciferase
reporter gene following transient transfection into NIH 3T3 cells, suggesting that this region of the gene is responsible
for transcriptional regulation of the TIS10 gene by mitogens in fibroblasts. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0021-9258 1083-351X |
DOI: | 10.1016/S0021-9258(18)42840-2 |