Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.27.5 (RNase)
 17,967 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The concentration of immunoreactive protein in the cytosol of L1210 cells measured using a specific radioimmunoassay for dihydrofolate reductase was substantially greater than the concentration of active enzyme which was measured by the binding of [3H]methotrexate. When the cytosol was subjected to gel filtration, two immunoreactive proteins were separated, a high-molecular-weight (Mr 318,000) protein which did not have catalytic activity and which did not bind [3H]methotrexate and a smaller protein (Mr approximately 20,000) which did reduce [3H]folic acid to tetrahydrofolate and did bind [3H]methotrexate. The nonfunctional high-molecular-weight protein neutralized the inhibitory effect of the antiserum on active dihydrofolate reductase. There was no spontaneous disaggregation of the big species into smaller subunits nor did 8 M urea alone, dithioerythritol alone, boiling with a mixture of 8 M urea and dithioerythritol, or RNase alter its apparent molecular weight. Trypsin, however, digested both the nonfunctional and active immunoreactive forms of the enzyme. Isoelectric focusing of the cytosol separated two nonfunctional immunoreactive isoproteins, each having the same isoelectric points as the two active isoenzymes of dihydrofolate reductase (pls of 8.0 and 8.5). Studies in rapidly replicating and stationary-phase L1210 cells showed that the concentration of the nonfunctional immunoreactive protein increased rapidly, reaching a peak on Day 2 of log growth at which time active enzyme was at a nadir, and then decreased rapidly, reaching a nadir on Day 4, at which time active enzyme was at a peak. The identical isoelectric points for the inactive and active immunoreactive proteins and the reciprocal concentration of each form in logarithmically growing cells suggest that the immunoreactive large species may be a precursor of the active enzyme.
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PMID:Identification of a high-molecular-weight nonfunctional protein in L1210 leukemia cells with common antigenic determinants to dihydrofolate reductase. 618 48

The eukaryotic trifunctional enzyme, C(1)-tetrahydrofolate (THF) synthase, interconverts folic acid derivatives between various oxidation states and is critical for normal cellular function, growth, and differentiation. Using a rat C(1)-THF synthase cDNA and synthetic oligonucleotides, the rat C(1)-THF synthase gene was isolated and characterized. The gene consists of 28 exons and spans 67.5 kbp. Primer extension, RNase protection, and rapid amplification of cDNA ends (RACE) experiments indicate the presence of multiple transcription start points (tsp) within a 250-bp window located between 50 and 300 bp upstream from the start codon. The 5' flanking region is devoid of a TATA consensus sequence motif, but putative regulatory elements, including NF-kappabeta, HNF-4alpha1, RARalpha1, C/EBP, and PPAR are present in the promoter region. The 5' flanking region also contains two sets of tetranucleotide repeats and two short interspersed nuclear elements (SINES). The initial 2500 bp of 5' flanking sequences of the rat and mouse cytoplasmic C(1)-THF synthase genes share 70% identity. However, comparison with the human gene from the Human Genome Data Bank revealed no significant homology in the 5' flanking region. The gene structure characterization led to the identification of a pseudogene that is 94% identical to the C(1)-THF synthase gene and probably diverged 10-12 million years ago. In addition, the gene expression patterns of C(1)-THF synthase were investigated during liver regeneration and liver and kidney organogenesis, two highly regulated events. In both processes, C(1)-THF synthase expression correlated with increased nucleotide metabolism. This pattern suggests that the gene is regulated in response to changes in the demand for folate-dependent one-carbon units.
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PMID:Characterization of the rat cytoplasmic C1-tetrahydrofolate synthase gene and analysis of its expression in liver regeneration and fetal development. 1459 74