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Human adrenodoxin reductase: two mRNAs encoded by a single gene on chromosome 17cen----q25 are expressed in steroidogenic tissues. 总被引:8,自引:4,他引:4 下载免费PDF全文
S B Solish J Picado-Leonard Y Morel R W Kuhn T K Mohandas I Hanukoglu W L Miller 《Proceedings of the National Academy of Sciences of the United States of America》1988,85(19):7104-7108
Adrenodoxin reductase is a mitochondrial flavoprotein that receives electrons from NADPH, thus initiating the electron-transport chain serving mitochondrial cytochromes P450. We have cloned and sequenced two human adrenodoxin reductase cDNAs that differ by the presence of six additional codons in the middle of one clone. The sequence in this region indicates that these six extra codons arise by alternative splicing of the pre-mRNA. Southern blot hybridization patterns of human genomic DNA cut with four restriction enzymes indicate that the human genome has only one gene for adrenodoxin reductase. Analysis of a panel of mouse-human somatic cell hybrids localized this gene to chromosome 17cen----q25. The alternatively spliced mRNA containing the six extra codons represents 10-20% of all adrenodoxin reductase mRNA. The expression of the adrenodoxin reductase gene may be stimulated by pituitary tropic hormones acting through cAMP, but its response is quantitatively much less than the responses of P450scc and adrenodoxin. 相似文献
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Sequence arrangement of the 5'' ends of simian virus 40 16S and 19S mRNAs. 总被引:14,自引:2,他引:14 下载免费PDF全文
M T Hsu J Ford 《Proceedings of the National Academy of Sciences of the United States of America》1977,74(11):4982-4985
Electron microscopic examination of molecular hybrids between simian virus 40 DNA, that had been cleaved with EcoRI and then digested with exonuclease III, and either 16S or 19S mRNA produced late during the viral infection cycle indicated that each of these mRNAs contained a 5'-terminal "leader" sequence that was encoded in the viral genome at about map position 0.71-0.75. Hybridization of each of these mRNAs to viral DNA immobilized on nitrocellulose filters supported the electron microscopic observations. 相似文献
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C Labbaye P Musette Y E Cayre 《Proceedings of the National Academy of Sciences of the United States of America》1991,88(20):9253-9256
Myeloblastin is a serine protease that has been identified in the human leukemia cell line HL-60. Down-regulation of this protease can inhibit proliferation and induce differentiation of promyelocyte-like human leukemic cells. Proteinase 3, a serine protease of human neutrophils, has been identified as the Wegener autoantigen. A high level of homology between myeloblastin and proteinase 3 has suggested that they may be a single serine protease. We have recently completed the 5'-terminal nucleotide sequence of proteinase 3 and shown that its mRNA was also expressed in HL-60 cells and in cells from patients with acute myeloid leukemia. Here we demonstrate that myeloblastin and proteinase 3 are encoded by a single mRNA. 相似文献
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Two prohormones for gastrin-releasing peptide are encoded by two mRNAs differing by 19 nucleotides. 总被引:5,自引:3,他引:2
E R Spindel M D Zilberberg J F Habener W W Chin 《Proceedings of the National Academy of Sciences of the United States of America》1986,83(1):19-23
In our studies on the molecular biology of human gastrin-releasing peptide (GRP), we have discovered an example of a change in translational reading frame apparently produced through alternative RNA splicing. Complementary DNAs prepared from a pulmonary carcinoid tumor rich in GRP immunoreactivity had one of two different-sized internal DNA fragments after digestion with the restriction enzyme Pvu II. Nucleotide sequences of the two DNA fragments were identical except for 19 additional nucleotides present in the larger fragment. The region of the mRNA containing the 19 nucleotides corresponded to the carboxyl-terminal region of the human GRP precursor. The resulting shift in reading frame causes a difference of 10 amino acids in size and an overall sequence difference of 27 amino acids between the two GRP prohormones so formed. The change in reading frame described here is unusual in eukaryotes and is yet another mechanism to produce diversity in the generation of biological peptides. 相似文献
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Structural features of the acetyl-CoA carboxylase gene: mechanisms for the generation of mRNAs with 5'' end heterogeneity. 总被引:9,自引:3,他引:6 下载免费PDF全文
X C Luo K Park F Lopez-Casillas K H Kim 《Proceedings of the National Academy of Sciences of the United States of America》1989,86(11):4042-4046
Acetyl-CoA carboxylase [acetyl-CoA:carbondioxide ligase (ADP-forming), EC 6.4.1.2] is the rate-limiting enzyme in the biogenesis of long-chain fatty acids. We have previously characterized five acetyl-CoA carboxylase mRNA species that differ in their 5' untranslated regions but not in the coding region. We have now characterized the exon-intron structure of the genomic DNA that encodes the 5' untranslated region of the mRNA. Generation of different forms of the mRNA is the result of the selective use of two promoters and differential splicing of five different exons. These five exons contain a total of 645 nucleotides and they are scattered over a 50-kilobase-pair genomic DNA region that we have characterized. 相似文献
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DNA sequences preceding the rabbit beta-globin gene are required for formation in mouse L cells of beta-globin RNA with the correct 5'' terminus. 总被引:54,自引:15,他引:54 下载免费PDF全文
P Dierks A van Ooyen N Mantei C Weissmann 《Proceedings of the National Academy of Sciences of the United States of America》1981,78(3):1411-1415
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Two human glutamate decarboxylases, 65-kDa GAD and 67-kDa GAD, are each encoded by a single gene. 总被引:25,自引:3,他引:25 下载免费PDF全文
D F Bu M G Erlander B C Hitz N J Tillakaratne D L Kaufman C B Wagner-McPherson G A Evans A J Tobin 《Proceedings of the National Academy of Sciences of the United States of America》1992,89(6):2115-2119
We report the isolation and sequencing of cDNAs encoding two human glutamate decarboxylases (GADs; L-glutamate 1-carboxy-lyase, EC 4.1.1.15), GAD65 and GAD67. Human GAD65 cDNA encodes a Mr 65,000 polypeptide, with 585 amino acid residues, whereas human GAD67 encodes a Mr 67,000 polypeptide, with 594 amino acid residues. Both cDNAs direct the synthesis of enzymatically active GADs in bacterial expression systems. Each cDNA hybridizes to a single species of brain mRNA and to a specific set of restriction fragments in human genomic DNA. In situ hybridization of fluorescently labeled GAD probes to human chromosomes localizes the human GAD65 gene to chromosome 10p11.23 and the human GAD67 gene to chromosome 2q31. We conclude that GAD65 and GAD67 each derive from a single separate gene. The cDNAs we describe should allow the bacterial production of test antigens for the diagnosis and prediction of insulin-dependent diabetes mellitus. 相似文献
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Allelic variants of acetylcholinesterase: genetic evidence that all acetylcholinesterase forms in avian nerves and muscles are encoded by a single gene. 总被引:8,自引:1,他引:7 下载免费PDF全文
R L Rotundo A M Gomez C Fernandez-Valle W R Randall 《Proceedings of the National Academy of Sciences of the United States of America》1988,85(20):7805-7809
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Presecretory and cytoplasmic invertase polypeptides encoded by distinct mRNAs derived from the same structural gene differ by a signal sequence. 总被引:30,自引:5,他引:25 下载免费PDF全文
D Perlman H O Halvorson L E Cannon 《Proceedings of the National Academy of Sciences of the United States of America》1982,79(3):781-785
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Multiple purine pathway enzyme activities are encoded at a single genetic locus in Drosophila. 总被引:16,自引:2,他引:14
S Henikoff M A Keene J S Sloan J Bleskan R Hards D Patterson 《Proceedings of the National Academy of Sciences of the United States of America》1986,83(3):720-724
The Drosophila melanogaster Gart locus, known from previous work to encode the enzyme activity phosphoribosylglycinamide formyltransferase (GART), specifies two alternatively processed mRNAs and two proteins. We introduced the entire Gart locus into a Drosophila tissue culture cell line in which the locus is active. The resulting cell clones contained numerous copies of the locus and overproduced both mRNAs and both expected proteins, thus markedly facilitating analysis of these molecules. We assayed extracts of the clones for the activities of 10 enzymes important for de novo purine synthesis and found that, in addition to GART, two other purine pathway activities, phosphoribosylamine-glycine ligase (phosphoribosylglycinamide synthetase, GARS) and phosphoribosylformylglycinamidine cyclo-ligase (phosphoribosylaminoimidazole synthetase, AIRS), are similarly overproduced. All three activities are present together on the larger overproduced protein. A smaller protein appears to possess only GARS activity. Therefore, alternative mRNA processing can allow cells to produce enzyme activities in forms that are either linked or unlinked to other activities. 相似文献
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Functional expression of P-glycoprotein encoded by the mouse mdr3 gene in yeast cells. 总被引:1,自引:1,他引:1 下载免费PDF全文
S Ruetz M Raymond P Gros 《Proceedings of the National Academy of Sciences of the United States of America》1993,90(24):11588-11592
We have expressed P-glycoprotein (P-gp) encoded by the mouse mdr3 gene in the yeast Saccharomyces cerevisiae and have developed an experimental protocol to isolate and purify inside-out plasma membrane vesicles (IOVs) from these cells. Biochemical characterization of IOVs from control and P-gp-expressing cells isolated by this procedure show that they are greatly enriched for plasma membrane markers, are tightly sealed, and are competent for D-glucose transport. P-gp expression in these vesicles results in the appearance of a specific ATP-dependent and temperature-sensitive transport of the drugs colchicine and vinblastine that is osmotically sensitive. P-gp-mediated drug transport into these IOVs is inhibited by a known P-gp modulator, verapamil, and can be abrogated by prior incubation of the IOVs with an anti-P-gp antibody. A Ser-939-->Phe mutation within the predicted transmembrane domain 11 of P-gp, which is known to modulate its function in mammalian cells, drastically reduces drug transport in IOVs obtained from yeast cells expressing the mutant protein. The successful demonstration of active drug transport into IOVs from P-gp-expressing yeast cells indicates that P-gp can mediate both chemotherapeutic drugs and a-pheromone transport in yeast cells. 相似文献