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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1994-3-31
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pubmed:databankReference | |
pubmed:abstractText |
Mouse neuroblastoma cells (NB) selected for 10,000-fold increased resistance to mycophenolic acid (NB-Myco) showed a 200-500-fold increase in IMP dehydrogenase protein, and the enzyme (IMP: NAD+ oxidoreductase, EC 1.1.1.205) also exhibited a 2400-fold increased ki for mycophenolic acid and reduced catalytic efficiency (Hodges, S.D., Fung, E., McKay, D.J., Renaux, B.S., and Snyder, F.F. (1989) J. Biol. Chem. 264, 18137-18141). The molecular basis of these changes is the subject of the present study. The nucleotide sequence of IMP dehydrogenase cDNA from NB-Myco cells revealed four nucleotide changes. One of these changes did not result in a codon change, and a second one corresponding to methionine-483 was present in the parental NB mouse line. The remaining two nucleotide substitutions and deduced residue changes are: the C to T transition at base 998 relative to initiation of translation, altering threonine-333 to isoleucine; and the C to A transversion at base 1052, altering serine-351 to tyrosine. Evidence was also obtained for IMP dehydrogenase having undergone gene amplification. IMP dehydrogenase mRNA levels were 500-fold increased in NB-Myco cells as compared to parental NB cells. DNA dot blot analysis showed a 25-fold increase in IMP dehydrogenase gene copy number and restriction enzyme analysis revealed similar gene structure for NB and NB-myco cells.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Mar
|
pubmed:issn |
0006-3002
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
1217
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
156-62
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:7906545-Animals,
pubmed-meshheading:7906545-Base Sequence,
pubmed-meshheading:7906545-Cell Division,
pubmed-meshheading:7906545-Drug Resistance,
pubmed-meshheading:7906545-Gene Amplification,
pubmed-meshheading:7906545-IMP Dehydrogenase,
pubmed-meshheading:7906545-Mice,
pubmed-meshheading:7906545-Molecular Sequence Data,
pubmed-meshheading:7906545-Mycophenolic Acid,
pubmed-meshheading:7906545-Point Mutation,
pubmed-meshheading:7906545-RNA, Messenger,
pubmed-meshheading:7906545-Sequence Homology, Amino Acid,
pubmed-meshheading:7906545-Tumor Cells, Cultured
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pubmed:year |
1994
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pubmed:articleTitle |
Gene amplification and dual point mutations of mouse IMP dehydrogenase associated with cellular resistance to mycophenolic acid.
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pubmed:affiliation |
Department of Paediatrics, Faculty of Medicine, University of Calgary, Alberta, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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