L-methionine availability regulates expression of the methionine adenosyltransferase 2A gene in human hepatocarcinoma cells
L-methionine availability regulates expression of the methionine adenosyltransferase 2A gene in human hepatocarcinoma cells
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DOI：
10.1074/jbc.m211554200
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发表时间：
2003-05-30
影响因子：
4.8
通讯作者：
Avila, MA
中科院分区：
文献类型：
--
作者：
Martínez-Chantar, ML;Latasa, MU;Avila, MA
在哺乳动物中，甲硫氨酸腺苷转移酶（MAT）是负责S-腺苷甲硫氨酸（S-adenosylmethionine，MAT）合成的酶，由两个基因MAT 1A和MAT 2A编码。在肝脏中，MAT 1A表达与高的α-Met水平和分化表型相关，而MAT 2A表达与较低的α-Met水平和去分化表型相关。在目前的研究中，我们研究了MAT 2A基因表达的调节L-甲硫氨酸的可用性使用HepG 2细胞。在L-甲硫氨酸缺陷细胞中，MAT 2A基因表达被快速诱导，并且甲硫氨酸腺苷转移酶活性增加。L-甲硫氨酸的恢复迅速下调MAT 2A mRNA水平;为了达到这种效果，L-甲硫氨酸需要转化为蛋氨酸。这种新的行动，甲硫氨酸是不介导的甲基转移反应。MAT 2A基因表达也受5 '-甲硫基腺苷调节，但这依赖于5'-甲硫基腺苷通过补救途径转化为甲硫氨酸。MAT 2A基因的转录速率在L-甲硫氨酸饥饿期间保持不变;然而，其mRNA半衰期显著增加（从100 min增加到3 h以上）。L-甲硫氨酸停药对MAT 2A mRNA稳定的影响需要基因转录和蛋白质合成。我们的结论是，MAT 2A基因的表达是调制作为一个适应性反应的细胞L-甲硫氨酸的可用性，通过其转换为蛋氨酸。
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.