Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 5.8S rRNA of normal tissues contains a partially 2'-O-methylated uridylic acid residue which is methylated in the cytoplasm and undermethylated in rapidly growing neoplastic tissues (R. N. Nazar, T. O. Sitz, and K. D. Somers, J. Mol. Biol., 142: 117-121, 1980). This difference in methylation was further characterized by examining the effect of cell age or cell culture passage number on the level of methylation of 5.8S RNAs from normal and malignant cell lines and simultaneous changes in intracellular pools of S-adenosylmethionine and S-adenosylhomocysteine. The results indicate that the level of methylation decreases continuously with cell culture passage number as the cells become aneuploid, transformed, or tumorigenic, but there is no direct correlation with the intracellular pools of S-adenosylmethionine or S-adenosylhomocysteine. In contrast, there is a dramatic but inverse increase in the S-adenosylmethionine:S-adenosylhomocysteine ratio which correlates with the decreasing levels of 2'-O-methylation. The significance of these changes in substrate levels to the hypomethylation of 5.8S and other RNAs during oncogenesis is discussed.
 ...
PMID:Significance of S-adenosylmethionine pools in the hypomethylation of ribosomal RNA during the propagation of tissue culture cells and oncogenesis. 658 62

Diphthamide, a unique amino acid, is a post-translational derivative of histidine that exists in protein synthesis elongation factor 2 at the site of diphtheria toxin-catalyzed ADP-ribosylation of elongation factor 2. We investigated steps in the biosynthesis of diphthamide with mutants of Chinese hamster ovary cells that were altered in different steps of this complex post-translational modification. Biochemical evidence indicates that this modification requires a minimum of three steps, two of which we accomplished in vitro. We identified a methyltransferase activity that transfers methyl groups from S-adenosyl methionine to an unmethylated form of diphthine (the deamidated form of diphthamide), and we tentatively identified an ATP-dependent synthetase activity involved in the biosynthesis of diphthamide from diphthine. Our results are in accord with the proposed structure of diphthamide (B. G. VanNess, et al., J. Biol. Chem. 255:10710-10716, 1980).
Mol Cell Biol 1984 Apr
PMID:In vitro biosynthesis of diphthamide, studied with mutant Chinese hamster ovary cells resistant to diphtheria toxin. 671 39

Adenosine dialdehyde (2'-O-[(R)-formyl( adenin -9-yl)methyl]-(R) -glyceraldehyde), which is formed by periodate oxidation of adenosine, was shown to be a potent inhibitor of S- adenosylhomocysteine hydrolase (AdoHcy hydrolase; EC 3.3.1.1) in mouse L929 cells. The inhibitory effects of adenosine dialdehyde on AdoHcy hydrolase were time-dependent, having a rapid onset with complete inhibition occurring within a 15-min incubation period. When mouse L929 cells were preincubated with adenosine dialdehyde for 15 min, then transferred to fresh medium, the AdoHcy hydrolase activity returned to control values within 16 hr. When cycloheximide, an inhibitor of protein synthesis, was included in the incubation medium, recovery of AdoHcy hydrolase activity was not prevented, suggesting that the recovery of enzyme activity was probably due to slow reversal of the inhibitor-enzyme complex. The inhibition of AdoHcy hydrolase by adenosine dialdehyde resulted in a time-dependent increase in endogenous AdoHcy levels. After an initial 15-min lag time, the concentration of AdoHcy continued to increase, reaching a maximum of 1200 pmoles/mg of protein in 12 hr. A slight increase in AdoMet levels was observed. Incubation of mouse L929 cells with adenosine dialdehyde also caused an inhibition of lipid methylation and protein carboxylmethylation which resulted from the compound's effect on AdoHcy hydrolase and the subsequent buildup of endogenous AdoHcy levels. Under the conditions that produce inhibition of AdoHcy hydrolase and AdoMet-dependent methyltransferases, adenosine dialdehyde had no effect on RNA or DNA synthesis. Therefore, adenosine dialdehyde appears to be a useful chemical probe with which to study the physiological role of AdoMet-dependent methylations.
Mol Pharmacol 1984 May
PMID:Effects of adenosine dialdehyde on S-adenosylhomocysteine hydrolase and S-adenosylmethionine-dependent transmethylations in mouse L929 cells. 672 64

A fast method for a single-step fractionation of a number of tRNA methyltransferases from Salmonella typhimurium is described. The method basically consists of ion-exchange chromatography on a phosphocellulose column and permits the separation of the enzymes forming mt6A, m1G, m5U, m7G. The enzyme fractions appear sufficiently purified to allow the estimation of some molecular and kinetic properties. The apparent KM for adenosylmethionine range between 1.5 to 3.2 X 10(-5) M, whereas KM for undermethylated tRNA range between 3.1 X 10(-5) M to 3.1 X 10(-4) M. Glycerol gradient determination indicates the following Mr for the native proteins: 25 X 10(3), 40 X 10(3), 50 X 10(3) and 65 X 10(3) for m7G-, mt6A-, m1G- and m5U-forming enzymes, respectively. A complete analysis of methylated nucleosides formed in vivo in S. typhimurium has been obtained: it also allowed us to infer the pattern of the various tRNA methyltransferases for this prokaryote. The tRNA methyltransferase forming mt6A has been isolated for the first time from any type of cell.
Mol Cell Biochem 1981 Apr 27
PMID:Purification and properties of several transfer RNA methyltransferases from S. typhimurium. 678 7

Nitrous oxide administration to experimental animals leads to significant alterations in the hepatic folate pathway. This pathway is closely linked to the metabolism of methionine and S-adenosylmethionine (AdoMet), two compounds that play a central role in biologically important methylation reactions. This study was carried out to assess whether nitrous oxide administration to animals can affect the metabolism of AdoMet and the AdoMet-dependent methylation reactions. Exposure of rats to a mixture of nitrous oxide and oxygen (50:50) for 2 hr reduced hepatic AdoMet levels. However, when methionine was administered to these rats, hepatic AdoMet rapidly increased to levels that were significantly higher than those observed in air-exposed animals. Concomitant with this increase, there was a significant and marked increase in the rate of methylation of phospholipids and carboxymethylation of proteins. Thus, nitrous oxide, in addition to its inhibitory effect on 5-methyltetrahydrofolate:homocysteine methyltransferase (methionine synthase, EC 2.1.1.13) activity, possesses another effect. It increases the rate of conversion of exogenously administered methionine into AdoMet with a subsequent increase in the rate of methylation of key cellular constituents.
Mol Pharmacol 1983 Jul
PMID:Effect of nitrous oxide and methionine treatments on hepatic S-adenosylmethionine and methylation reactions in the rat. 686 21

The assay for the ksgA-encoded S-adenosylmethionine--6-N',N'-adenosyl (rRNA) dimethyltransferase has been improved; the gel-filtration molecular weight of partially purified enzyme under two different sets of conditions was found to be 55,000 or 26,000 daltons. We have determined methyltransferase activities in strains where ksgA was brought under the control of the mitomycin C-inducible promoter of the colicin E1 gene. Our studies show that ksgA is transcribed counterclockwise on the Escherichia coli chromosome.
Mol Gen Genet 1980
PMID:Some properties of the ribosomal RNA methyltransferase encoded by ksgA and the polarity of ksgA transcription. 700 24

A previous study showed that cultured Nb 2 node rat lymphoma cells stopped replicating when transferred to medium supplemented with horse serum instead of fetal calf serum; resumption of growth could be induced by the addition of prolactin or other lactogens. The present study shows that in the absence of prolactin cells accumulated early in the G1 phase from which, on stimulation by the hormone, they proceeded through the cell cycle in a synchronized fashion. Ornithine decarboxylase and S-adenosyl methionine decarboxylase activities were closely related to the proliferative status of the cells. In stationary cultures the enzyme activity was barely detectable; following the addition of prolactin, the levels increased over 100-fold and displayed well-defined changes as the cells proceeded through the cell cycle. The results suggest the lymphoma cells are very useful for studying biochemical events resulting from the interaction of a mitogenic polypeptide hormone and its target cell.
Mol Cell Endocrinol 1982 Apr
PMID:Biochemical response of lymphoma cells to mitogenic stimulation by prolactin. 708 63

Studies on the disposition of extracellular S-adenosylhomocysteine by isolated rat hepatocytes have shown that S-adenosyl-L-homocysteine is not taken up by cells, but binds to acceptor(s) on the cell surface. The Scatchard plots for the binding of S-adenosylhomocysteine to hepatocytes and purified rat liver membranes at 0 degrees were nonlinear, and consistent with high-affinity components with Kd values of 0.4 microM and 0.7 microM, respectively. About 60% of the S-adenosylhomocysteine that was bound to cells and purified membranes dissociated rapidly from its binding sites. The rapid initial phase was followed by a second slow phase obeying first-order kinetics, corresponding to a dissociation rate constant of 0.09 min-1. S-Tubercidinylhomocysteine and unlabeled S-adenosylhomocysteine were potent inhibitors of the binding of S-[14C]adenosylhomocysteine, whereas S-3-deazaadenosylhomocysteine, S-adenosylmethionine, and S-adenosyl-D-homocysteine were less effective. A fraction of the S-adenosylhomocysteine that was bound to rat hepatocytes was displaced by low concentrations of sinefungin and its metabolite, A9145C, but these compounds were weak inhibitors of S-adenosylhomocysteine binding to purified membranes. 5'-Deoxy-5'-S-isobutylthioadenosine showed slight inhibitory activity against S-adenosylhomocysteine binding to both cells and purified membranes. In conclusion, the equilibrium binding, dissociation rate kinetics, and displacement curves in the presence of S-adenosylhomocysteine analogues show that S-adenosylhomocysteine binds to a heterogeneous population of binding sites of intact hepatocytes and purified liver plasma membranes.
Mol Pharmacol 1982 Jan
PMID:Characterization of S-adenosylhomocysteine binding to isolated rat hepatocytes and purified rat liver plasma membranes. Effect of analogues of S-adenosylhomocysteine. 713 53

The age related decrease in alpha 1-adrenergic stimulated inositol 1, 4, 5 trisphosphate (IP3) production in parotid cells of aged rats can be partially restored by treatment with S-adenosylmethionine (SAM). This effect is completely blocked by S-adenosyl homocysteine (SAH) and occurs in association with an increase in the conversion of phosphatidylethanolamine to phosphatidylcholine and a decrease in membrane viscosity. In contrast, SAM treatment actually inhibits stimulated IP3 production in cells of young rats. The membrane viscosity of these cells is lower than that of those from aged rats. Although conversion of phosphatidylethanolamine to phosphatidylcholine is enhanced, no further decrease in membrane viscosity is elicited in young cell preparations. These findings suggest that age changes in the membrane environment may result in impaired alpha 1-adrenergic signal transduction and that such alterations may be at least partially reversible by SAM treatment.
Mol Cell Biochem 1995 Jul 05
PMID:Partial restoration of impaired alpha 1-adrenergic responsiveness in parotid cells of aged rats by S-adenosylmethionine treatment. 747 36

APP695 mRNA is only expressed in the brains of SAM. The expression of APP mRNA in SAM P1 mice brains is more marked than that in SAM R1 mice brain. APP mRNA expression was increased with advancing age in all brain regions of SAM P1 mice compared with SAM R1. Especially, the changes of the amount of APP mRNA in the prosencephalon and the mesencephalon are significant at P value of 0.05. We suggest that overexpression of APP mRNA may be related to accelerated aging phenomenon in the SAM brain. This is the first report of age-related increase in the amount of APP mRNA in the SAM brain.
Comp Biochem Physiol B Biochem Mol Biol 1995 Oct
PMID:Age-related changes of mRNA expression of amyloid precursor protein in the brain of senescence-accelerated mouse. 758 67


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>