Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.3.5.5 (CPS)
 1,262 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cis-diaminedichloroplatinum(II) [cDDP] and three related derivatives Pt(mal)(NH3)2, PtCl2(dach) and Pt(mal) (dach) have been observed to possess cytotoxicity against the growth of P388 lymphocytic leukemia cells. DNA synthesis in P388 cells was inhibited by the agents in a manner which was consistent with their ED50 values for cytotoxicity. When P388 cells were treated with these platinum complexes in vitro at doses which caused more than 80% inhibition of DNA synthesis, no significant inhibition was observed for thymidine, kinase, thymidine monophosphate kinase, carbamoyl phosphate synthetase, or aspartate transcarbamoylase activities. Thus, there was no evidence that these agents inhibited de novo purine, pyrmidine, or deoxynucleotide synthesis. All of the agents did inhibit the nuclear DNA polymerase activity, but the extent of inhibition was 20% or less at doses which caused greater than 70% inhibition of DNA synthesis. Thus, the inhibition of DNA synthesis appeared to be due to cisplatinum(II) drug binding to the DNA bases. This was estimated to be 1 atom of platinum per 1500-3000 DNA base pairs which is consistent with other studies. The platinum complexes with chloro leaving ligands caused considerable DNA strand scission by 24 h at 10 times the ED50 dose, most likely a measure of impending cell death. In contrast, the platinum complexes with malonato leaving ligands did not cause significant strand scission by 24 h at similar doses. They also exhibited a significant delay in the inhibition of DNA synthesis. These data were interpreted as resulting from slower monoadduct to diadduct conversion, but it is not possible to eliminate the possibility of a different mode of interaction with DNA or a different mechanism of cytotoxicity for the malonato compounds.
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PMID:Inhibition of nucleic acid synthesis in P388 lymphocytic leukemia cells in culture by cis-platinum derivatives. 170 16

1. The incorporation of thymidine into DNA of regenerating rat liver was measured at various times after partial hepatectomy. A single intravenous injection of 30mumol of beryllium/kg given immediately after the operation inhibited DNA synthesis 12, 16, 20, 24 and 28h later. 2. The activity of several enzymes critical to DNA synthesis (thymidine kinase, thymidylate kinase, thymidylate synthetase, deoxycytidylate deaminase and DNA polymerase) increased in control rats 20-24h after partial hepatectomy severalfold over the activity found in resting livers. After beryllium treatment this rise in activity was much less and it seemed as if beryllium would partially block the induction of DNA-synthesizing enzymes after partial hepatectomy. 3. Enzymes whose activities do not rise during liver regeneration were not affected by beryllium (aspartate transcarbamoylase, carbamoyl phosphate synthetase, uridine kinase and glucose 6-phosphatase). 4. No evidence was found in vitro that beryllium would specifically inhibit thymidine kinase or DNA polymerase. 5. The time-effect relationship between beryllium administration and thymidine kinase activity in vivo was examined. Measured 24h after partial hepatectomy, thymidine kinase activity was only affected if beryllium was given within the first 9-12h after partial hepatectomy. Beryllium given later, even in greatly increased doses, failed to have any effect on thymidine kinase. The possibility is discussed that beryllium inhibits enzyme induction at the transcriptional level.
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PMID:Effects of beryllium on deoxyribonucleic acid-synthesizing enzymes in regenerating rat liver. 549 75

CCAAT-displacement protein/Cut homeobox (CDP/Cux) was initially identified as a transcriptional repressor. However, a number of studies have now suggested that CDP/Cux is a transcriptional activator as well. Stable DNA binding activity of CDP/Cux is up-regulated at the G(1)/S transition by two mechanisms, dephosphorylation by the Cdc25A phosphatase and proteolytic processing to generate a 110 kDa amino-truncated isoform, CDP/Cux p110. The generation of CDP/Cux p110 stimulates the expression of reporter plasmid containing the promoter sequences of some S phase-specific-genes such as DNA polymerase a gene, dihydrofolate reductase gene, carbamoyl-phosphate synthase/aspartate carbamoyl-transferase/dihydroorotase gene, and cyclin A gene. However, DNA binding activity of CDP/Cux is down-regulated at G(2) phase through a binding of cyclin A-cyclin-dependent kinases1 (Cdk1) to CDP/Cux. Furthermore, another CDP/Cux isoform, CDP/Cux p75, has been found to be associated with breast tumors indicating this isoform is involved in the abnormal proliferation of tumor cells. The differences in DNA binding of CDP/Cux isoforms in S and G(2) phases suggest important roles of CDP/Cux in cell cycle progression. In this review, we discuss the functions of CDP/Cux with a focus on its roles in cell cycle regulation and its possible potency leading to the cell cycle reentry of neurons.
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PMID:Contribution of CDP/Cux, a transcription factor, to cell cycle progression. 1806 84