rdf:type |
|
lifeskim:mentions |
umls-concept:C0010798,
umls-concept:C0017337,
umls-concept:C0031412,
umls-concept:C0033268,
umls-concept:C0037473,
umls-concept:C0037494,
umls-concept:C0085542,
umls-concept:C0128665,
umls-concept:C0360714,
umls-concept:C1011185,
umls-concept:C1158770,
umls-concept:C1292724,
umls-concept:C1521991
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pubmed:issue |
1
|
pubmed:dateCreated |
1998-5-18
|
pubmed:abstractText |
We have characterized the transcriptional regulation of ML-236B.Na and phenobarbital-inducible cytochrome P450sca-2 (CytP450sca-2) from Streptomyces carbophilus, an industrial pravastatin-producing strain. ML-236B.Na and phenobarbital enhanced the expression of the cytP450sca-2 gene in S. carbophilus. The cytP450sca-2 gene was also ML-236B.Na-inductive in S. lividans. Analysis of various deletion and mutation of the 5'-flanking region of the cytP450sca-2 gene revealed that the 1-kb region was required for ML-236B.Na-dependent CytP450sca-2 induction. We have found a putative ORF in the 5'-flanking region that encodes a protein of 174 amino acid residues containing a helix-turn-helix DNA-binding motif. A gel mobility shift assay showed that the protein was bound by an imperfect palindromic sequence between -46bp and -24bp in the 5'-flanking region, and ML-236B.Na was found to inhibit its binding. These findings suggest that induction of cytP450sca-2 is negatively regulated at the transcriptional level and that the protein encoded by the putative ORF is possibly functional as a repressor of the cytP450sca-2 gene.
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pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Anticholesteremic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Antifungal Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 Enzyme System,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxymethylglutaryl-CoA...,
http://linkedlifedata.com/resource/pubmed/chemical/Lovastatin,
http://linkedlifedata.com/resource/pubmed/chemical/Mixed Function Oxygenases,
http://linkedlifedata.com/resource/pubmed/chemical/Phenobarbital,
http://linkedlifedata.com/resource/pubmed/chemical/Pravastatin,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/compactin,
http://linkedlifedata.com/resource/pubmed/chemical/mevastatin hydroxylase
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0378-1119
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pubmed:author |
|
pubmed:issnType |
Print
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pubmed:day |
27
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pubmed:volume |
210
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pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
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pubmed:pagination |
109-16
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:9524240-Amino Acid Sequence,
pubmed-meshheading:9524240-Anticholesteremic Agents,
pubmed-meshheading:9524240-Antifungal Agents,
pubmed-meshheading:9524240-Base Sequence,
pubmed-meshheading:9524240-Cloning, Molecular,
pubmed-meshheading:9524240-Cytochrome P-450 Enzyme System,
pubmed-meshheading:9524240-DNA Mutational Analysis,
pubmed-meshheading:9524240-DNA-Binding Proteins,
pubmed-meshheading:9524240-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:9524240-Gene Expression Regulation, Fungal,
pubmed-meshheading:9524240-Hydroxymethylglutaryl-CoA Reductase Inhibitors,
pubmed-meshheading:9524240-Lovastatin,
pubmed-meshheading:9524240-Mixed Function Oxygenases,
pubmed-meshheading:9524240-Molecular Sequence Data,
pubmed-meshheading:9524240-Phenobarbital,
pubmed-meshheading:9524240-Pravastatin,
pubmed-meshheading:9524240-RNA, Messenger,
pubmed-meshheading:9524240-Repressor Proteins,
pubmed-meshheading:9524240-Sequence Analysis, DNA,
pubmed-meshheading:9524240-Streptomyces,
pubmed-meshheading:9524240-Up-Regulation
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pubmed:year |
1998
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pubmed:articleTitle |
Molecular approaches for production of pravastatin, a HMG-CoA reductase inhibitor: transcriptional regulation of the cytochrome p450sca gene from Streptomyces carbophilus by ML-236B sodium salt and phenobarbital.
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pubmed:affiliation |
Biomedical Research Laboratories, Sankyo Co. Ltd, 1-2-58, Hiromachi, Shinagawa-ku, Tokyo 140, Japan.
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pubmed:publicationType |
Journal Article
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