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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polyamines are known to be essential for normal cell growth and differentiation. However, despite numerous studies, specific cellular functions of polyamines in general and individual polyamines in particular have remained only tentative, because of a lack of appropriate cell lines in which genes of polyamine-synthesizing enzymes have been disrupted by gene targeting. With the use of homologous recombination technique, we disrupted the gene encoding spermine synthase in mouse embryonic stem cells. The spermine synthase gene is located on X chromosome in mouse and, because the cells used in this study were of XY karyotype, a single targeting event was sufficient to result in null genotype. The targeted cells did not have any measurable spermine synthase activity and were totally devoid of the polyamine spermine. Spermine deficiency led to a substantial increase in spermidine content, but the total polyamine content was nearly unchanged. Despite the lack of spermine, these cells displayed a growth rate that was nearly similar to that of the parental cells and showed no overt morphological changes. However, the spermine-deficient cells were significantly more sensitive to the growth inhibition exerted by 2-difluoromethylornithine, an inhibitor of ornithine decarboxylase. Similarly, methylglyoxal bis(guanylhydrazone), an inhibitor of S-adenosylmethionine decarboxylase, and diethylnorspermine, a polyamine analog, although exerting cytostatic growth inhibition on wild-type cells, were clearly cytotoxic to the spermine-deficient cells. The spermine-deficient cells were also much more sensitive to etoposide-induced DNA damage than their wild-type counterparts.
Mol Pharmacol 2001 Feb
PMID:Spermine deficiency resulting from targeted disruption of the spermine synthase gene in embryonic stem cells leads to enhanced sensitivity to antiproliferative drugs. 1116 Aug 58

In the present study, the expression and the regulation of ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC) was examined in a series of oncogene transformed cell lines. The expression of both ODC and SAMDC was found to correlate with the nature of the oncogene expressed and with the resulting cellular phenotype expressed. This study demonstrates, for the first time, that the expression of both ODC and SAMDC increases as a function of cellular transformation and, in particular, as a function of malignant progression. Ras transformed cells were shown to express a unique regulatory mechanism whereby a co-ordinate up-regulation of the expression of both ODC and SAMDC occurs (via post-transcriptional stabilization of their mRNA transcripts) in the presence of protein synthesis inhibition. Altered expression (and regulation) of both ODC and SAMDC is suggested to constitute an important part of an altered growth regulatory program inherent to oncogene transformed cells, in particular, to transformed cells capable of malignant progression.
Mol Cell Biochem 2000 Dec
PMID:Altered ornithine decarboxylase and S-adenosylmethionine decarboxylase expression and regulation in mouse fibroblasts transformed with oncogenes or constitutively active Mitogen-Activated Protein (MAP) kinase kinase. 1120 59

Differential cDNA display and quantitative RT-PCR revealed that mRNA of host S-adenosylmethionine decarboxylase (SAMDC) was abundant only in the aphid endosymbiotic system well organized in young hosts, suggesting that SAMDC plays some important roles in the system. SAMDC is a key enzyme to synthesize polyamines that are known to be involved in a large array of biological events including protein synthesis, DNA stabilization, DNA replication, and cell proliferation. As the first step to investigate roles of polyamines in the endosymbiotic system, polyamine composition in bacteriocytes was determined by high performance liquid chromatography. As a result, we found that bacteriocytes contained virtually an only single polyamine, spermidine. The spermidine content of bacteriocytes fluctuated with time in the course of development and aging of the host aphid. This is the first report of polyamine assessment in a prokaryote-eukaryote endocellular symbiotic system, which demonstrated a unique polyamine composition.
Insect Biochem Mol Biol 2001 Mar 15
PMID:Expression of host S-adenosylmethionine decarboxylase gene and polyamine composition in aphid bacteriocytes. 1122 59

Omithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC) expression was investigated in NIH-3T3 fibroblasts that secrete K-FGF. Correlations between altered ODC and SAMDC expression and malignant potential were determined. Increased ODC and SAMDC expression was associated with increased expression of both ODC and SAMDC mRNA and enzyme activity levels. Transcriptional and post-transcriptional regulatory mechanisms were found to account for the increased expression of both ODC and SAMDC. Amplification of the ODC gene also played a role. Correlations between the expression of ODC and the invasion ability of the K-FGF overexpressing cells were also found. Additionally, putrescine, which is a cellular polyamine, was found to play a role in determining the nature of the invasive capacity of the K-FGF overexpressing cells. The results of this study which established correlations between alterations in the expression of ODC and SAMDC, the key rate limiting and regulatory activities in the synthesis of cellular polyamines, and malignant potential as a consequence of K-FGF overexpression supports a model which suggests that growth factor modulation of ODC and SAMDC expression is part of the altered growth regulatory program associated with cellular transformation and malignant progression.
Mol Cell Biochem 2002 Apr
PMID:K-FGF mediated transformation and induction of metastatic potential involves altered ornithine decarboxylase and S-adenosylmethionine decarboxylase expression--role in cellular invasion. 1208 79

The adaptive hyperplasia of the residual intestine after a massive bowel resection is not fully understood. We investigated the alterations in polyamine and glucose-related enzyme mRNA expression during intestinal adaptation. Six-week-old male Wistar rats underwent an 80% resection of the small intestine. The residual ileum was removed on the preoperative day (control) and on postoperative day (POD) 1, 3, 5 and 7. The total RNA was extracted from the mucosa, and a Northern blot analysis was performed. In the residual small intestine, the expression of polyamine synthesis enzymes, ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC) mRNAs were increased on POD 1. The expression of polyamine degradation enzymes diamine oxidase (DAO) and spermidine/spermine N1-acetyltransferase (SSAT) mRNA did not change dramatically. Antizyme-1 (AZ-1) mRNA was significantly increased on POD 1. The mRNA expression of glucose absorption and metabolism-related proteins, including the Na+-dependent D-glucose cotransporter (SGLT1), fructose-6-phosphate,2-kinase/fructose-2,6-bisphosphatase (Fru-6-P,2-kinase/Fru-2,6-Pase) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were only slightly changed on POD 1. The enzymes responsible for polyamine biosynthesis but not catabolism were upregulated at the translational level in enterocytes after a small bowel resection. The expression of glucose transport and glycolysis enzyme mRNAs did not increase after a small bowel resection.
Int J Mol Med 2002 Oct
PMID:Alteration in expression of polyamine and glucose-related enzyme mRNA after small bowel resection in the rat residual ileum. 1223 99

The Arabidopsis thaliana S-Adenosylmethionine decarboxylase (AdoMetDC) cDNA (GenBank U63633) was cloned. Site-specific mutagenesis was performed to introduce mutations at the conserved cysteine Cys(50), Cys(83), and Cys(230), and lys(81) residues. In accordance with the human AdoMetDC, the C50A and C230A mutagenesis had minimal effect on catalytic activity, which was further supported by DTNB-mediated inactivation and reactivation. However, unlike the human AdoMetDC, the Cys(50) and Cys(230) mutants were much more thermally unstable than the wild type and other mutant AdoMetDC, suggesting the structural significance of cysteines. Furthermore, according to a circular dichroism spectrum analysis, the Cys(50) and Cys(230) mutants show a higher a-helix content and lower coiled-coil content when compared to that of wild type and the other mutant AdoMetDC. Also, the three-dimensional structure of Arabidopsis thaliana AdoMetDC could further support all of the data presented here. Summarily, we suggest that the Cys(50) and Cys(230) residues are structurally important.
J Biochem Mol Biol 2002 Mar 31
PMID:Structural roles of cysteine 50 and cysteine 230 residues in Arabidopsis thaliana S-adenosylmethionine decarboxylase. 1229 27

Polyamines are aliphatic cations present in all cells. In normal cells, polyamine levels are intricately controlled by biosynthetic and catabolic enzymes. The biosynthetic enzymes are ornithine decarboxylase, S-adenosylmethionine decarboxylase, spermidine synthase, and spermine synthase. The catabolic enzymes include spermidine/spermine acetyltransferase, flavin containing polyamine oxidase, copper containing diamine oxidase, and possibly other amine oxidases. Multiple abnormalities in the control of polyamine metabolism and uptake might be responsible for increased levels of polyamines in cancer cells as compared to that of normal cells. This review is designed to look at the current research in polyamine biosynthesis, catabolism, and transport pathways, enumerate the functions of polyamines, and assess the potential for using polyamine metabolism or function as targets for cancer therapy.
J Cell Mol Med
PMID:Polyamine metabolism and cancer. 1292 50

We have investigated the regulation of the rice (Oryza sativa) gene OsSAMDC, which encodes an S-adenosyl-L-methionine decarboxylase (SAMDC) involved in polyamine biosynthesis. Clones representing genes differentially expressed at 5 degrees C and 20 degrees C were isolated from a cDNA library prepared from the chilling-tolerant japonica-type cultivar Yukihikari. The full-length OsSAMDC cDNA consists of 1560 bp, with the longest ORF encoding a polypeptide of 398 amino acids. Southern analysis indicated that there are two types of gene for SAMDC in the Yukihikari genome. Analysis of the expression of OsSAMDC by Northern hybridization revealed relatively high levels of mRNA in the leaves, nodes and internodes. We also analyzed the response of OsSAMDC to various abiotic stress treatments and plant hormones. Upon exposure to cold stress (5 degrees C) the level of OsSAMDC transcripts in the cold-resistant Yukihikari genotype continued to increase for up to 72 h. In contrast, there was no change in OsSAMDC transcription in the susceptible indica cultivar TKM9 under the same conditions. Ethephon induced the accumulation of OsSAMDC transcripts to similar extents in both genotypes. Examination of polyamine levels in the cold-resistant Yukihikari genotype revealed that spermidine levels were elevated during the course of cold treatment. These results suggest that the induction of the OsSAMDC gene in response to cold may be used as a molecular marker for the ability of rice seedlings to withstand exposure to low temperatures.
Mol Genet Genomics 2004 Mar
PMID:Differential expression of an S-adenosyl-L-methionine decarboxylase gene involved in polyamine biosynthesis under low temperature stress in japonica and indica rice genotypes. 1472 83

The suggestion has been made that polyamines may be involved in the control of cell death, since exceedingly high or low levels induce apoptosis in different cell systems. For a deeper insight into the relationship between apoptosis and polyamine metabolism, we investigated in vitro the effect on rat thymocytes of mitoguazone (MGBG, which inhibits S-adenosylmethionine decarboxylase, i.e. a key enzyme in the polyamine biosynthetic pathway). Thymocytes were selected as an especially suitable model system, since they undergo spontaneous apoptosis in vivo and can be easily induced to apoptose in vitro by etoposide, used here as an apoptogenic agent. MGBG protected thymocytes from both spontaneous and drug-induced apoptosis, and this protective effect was associated with a decrease in polyamine oxidase activity and total polyamine levels.
Cell Mol Life Sci 2004 Nov
PMID:Administration of the antitumor drug mitoguazone protects normal thymocytes against spontaneous and etoposide-induced apoptosis. 1554 80

In the malaria parasite, the two main regulatory activities of polyamine biosynthesis, ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC) occur in a single bifunctional protein. The AdoMetDC domain was modeled using the human and potato X-ray crystal structures as templates. Three parasite-specific inserts and the core active site region was identified using a structure-based alignment approach. The domain was modeled without the two largest inserts, to give a root mean square deviation of 1.85 angstroms from the human template. Contact with the rest of the bifunctional complex is predicted to occur on one face of the Plasmodium falciparum AdoMetDC (PfAdoMetDC) domain. In the active site there are four substitutions compared to the human template. One of these substitutions may be responsible for the lack of inhibition by Tris, compared to mammalian AdoMetDC. The model also provides an explanation for the lack of putrescine stimulation in PfAdoMetDC compared to mammalian AdoMetDC. A network of residues that connects the putrescine-binding site with the active site in human AdoMetDC is conserved in the malarial and plant cognates. Internal basic residues are found to assume the role of putrescine, based on the model and site-directed mutagenesis: Arg11 is absolutely required for normal activity, while disrupting Lys15 and Lys215 each cause 50% inhibition of AdoMetDC activity. These novel features of malarial AdoMetDC suggest possibilities for the discovery of parasite-specific inhibitors.
J Mol Graph Model 2006 Jan
PMID:Novel properties of malarial S-adenosylmethionine decarboxylase as revealed by structural modelling. 1625 47


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