Source:http://linkedlifedata.com/resource/pubmed/id/12660248
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
22
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pubmed:dateCreated |
2003-5-26
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pubmed:abstractText |
In mammals, methionine adenosyltransferase (MAT), the enzyme responsible for S-adenosylmethionine (AdoMet) synthesis, is encoded by two genes, MAT1A and MAT2A. In liver, MAT1A expression is associated with high AdoMet levels and a differentiated phenotype, whereas MAT2A expression is associated with lower AdoMet levels and a dedifferentiated phenotype. In the current study, we examined regulation of MAT2A gene expression by l-methionine availability using HepG2 cells. In l-methionine-deficient cells, MAT2A gene expression is rapidly induced, and methionine adenosyltransferase activity is increased. Restoration of l-methionine rapidly down-regulates MAT2A mRNA levels; for this effect, l-methionine needs to be converted into AdoMet. This novel action of AdoMet is not mediated through a methyl transfer reaction. MAT2A gene expression was also regulated by 5'-methylthioadenosine, but this was dependent on 5'-methylthioadenosine conversion to methionine through the salvage pathway. The transcription rate of the MAT2A gene remained unchanged during l-methionine starvation; however, its mRNA half-life was significantly increased (from 100 min to more than 3 h). The effect of l-methionine withdrawal on MAT2A mRNA stabilization requires both gene transcription and protein synthesis. We conclude that MAT2A gene expression is modulated as an adaptive response of the cell to l-methionine availability through its conversion to AdoMet.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
30
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pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
19885-90
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:12660248-Carcinoma, Hepatocellular,
pubmed-meshheading:12660248-Humans,
pubmed-meshheading:12660248-Liver Neoplasms,
pubmed-meshheading:12660248-Methionine,
pubmed-meshheading:12660248-Methionine Adenosyltransferase,
pubmed-meshheading:12660248-RNA, Messenger,
pubmed-meshheading:12660248-S-Adenosylmethionine,
pubmed-meshheading:12660248-Tumor Cells, Cultured
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pubmed:year |
2003
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pubmed:articleTitle |
L-methionine availability regulates expression of the methionine adenosyltransferase 2A gene in human hepatocarcinoma cells: role of S-adenosylmethionine.
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pubmed:affiliation |
Laboratorio de Proteómica, Genómica y Bioinformática, and División de Hepatología y Terapia Génica, Universidad de Navarra, Facultad de Medicina, 31008 Pamplona, Spain.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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