Disease relevance of Mtap

• Molecular characterization of 5'-deoxy-5'-methylthioadenosine phosphorylase-deficient mutant clones of murine lymphoma cell line R1.1 [1].
• Similar changes in polyamine metabolism were observed in a secondary mutant deficient in MTA phosphorylase, but resistant to MTA toxicity [2].
• The two lines are murine lymphocytic leukemia cells which differ in their ability to metabolize 5'-methylthioadenosine, the by-product of polyamine biosynthesis: L5178Y cells contain a specific 5'-methylthioadenosine phosphorylase; L1210 cells do not [3].
• Overexpression of MSAP enhanced the motility of glioma cells measured in matrigel invasion chambers and using a scratch assay [4].
• An analog of MTA, 5'-deoxy-5'-(hydroxyethylthio)adenosine (HETA), is a substrate for trypanosome MTA phosphorylase and is active in vitro and in vivo against Trypanosoma brucei brucei, an agent of bovine trypanosomiasis [5].

High impact information on Mtap

• It is apparent, however, that the presence or absence of methylthioadenosine phosphorylase does not substantially modulate the antiproliferative activity of ornithine decarboxylase inhibitors.(ABSTRACT TRUNCATED AT 400 WORDS)[3]
• We report altered expression of genes encoding ribosomal protein S3a and methylthioadenosine phosphorylase, suggesting such cellular growth and proliferation perturbations may occur in homozygous CBS-deficient mice liver [6].
• To test this theory, various purified preparations of bovine liver methylthioadenosine phosphorylase were used to artificially increase the specific activity of methylthioadenosine phosphorylase in horse serum [7].
• The growth responses of 5-deoxy-5-methylthioribose on a 5'-deoxy-5'-methylthioadenosine phosphorylase containing cell line (BW5147) and the methylthioadenosine phosphorylase-deficient cell line (L1210D) were examined [7].
• The enzyme methylthioadenosine phosphorylase functions in both purine and polyamine metabolism is dividing mammalian cells [8].

Chemical compound and disease context of Mtap

• Here we show that MRLC-interacting protein (MIR)-interacting saposin-like protein (MSAP) enhances cell spreading in fibroblasts and migration of rat C6 glioma cells through increases in MRLC phosphorylation [4].

Biological context of Mtap

• Biochemical genetic analysis of the role of methylthioadenosine phosphorylase in a murine lymphoid cell line [8].
• To determine the effects of the loss of this enzyme on cell growth and metabolism, we selected two methylthioadenosine phosphorylase-deficient mutant clones of the transplantable murine T lymphoma cell line R1 [8].
• The present results show that MSAP controls glioma cell migration via enhancement of MRLC phosphorylation [4].
• Thus, MSAP is a novel modulator of cell motility that influences migration of glioma cells and possibly other tumors [4].
• Downregulation of MSAP by RNA interference significantly decreased glioma cell migration and phosphorylation of MRLC [4].

Anatomical context of Mtap

• The MTA phosphorylase-containing tumor cell lines, especially of human origin, were found to be more sensitive to treatment by these analogues [9].
• Carp MSAP is exclusively transcribed in testis, while mouse meichroacidin message is present in gonads of both sexes, although especially enriched in testis [10].
• In mouse, meichroacidin is expressed in male germ cells of meiotic stages, while carp MSAP is expressed during late spermiogenesis and accumulated in mature spermatozoa, in which MSAP is localized to the basal body and flagellum [10].
• MTAP expression was determined in liver, bone marrow, small intestinal mucosa, and P388 cells [11].
• The use of methylthioadenosine phosphorylase activity to select for human chromosome 9 in interspecies and intraspecies hybrid cells [12].

Associations of Mtap with chemical compounds

• 5'-Deoxy-5'-(methylthio)adenosine (MTA), a key by-product of polyamine biosynthesis, is cleaved by MTA phosphorylase and is salvaged as adenine and, through conversion of the ribose moiety, methionine [5].
• Compound 9 was a potent competitive inhibitor of MTA phosphorylase with a Ki value of 3.3 microM and was also a substrate, with activity approximately 53% that of MTA [13].
• In contrast, 5'-methylthiotubercidin caused a large accumulation of extracellular 5'-methylthioadenosine with a concomitant smaller increase intracellularly in 5'-methylthioadenosine phosphorylase-containing cells [14].
• The antiproliferative effects of 5'-methylthioadenosine and the 5'-methylthioadenosine analogs, 5'-isobutylthioadenosine, 5'-deoxyadenosine and 5'-methylthiotubercidin were examined using two mouse cell lines, one 5'-methylthioadenosine phosphorylase-deficient the other containing 5'-methylthioadenosine phosphorylase [14].

References