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首页> 外文期刊>Parasitology >Leishmania donovani: proteasome-mediated down-regulation of methionine adenosyltransferase.
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Leishmania donovani: proteasome-mediated down-regulation of methionine adenosyltransferase.

机译：Leishmania donovani：蛋白酶体介导的蛋氨酸腺苷基转移酶的下调。

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SUMMARYMethionine adenosyltransferase (MAT) is an important enzyme for metabolic processes, to the extent that its product, S-adenosylmethionine (AdoMet), plays a key role in trans-methylation, trans-sulphuration and polyamine synthesis. Previous studies have shown that a MAT-overexpressing strain of Leishmania donovani controls AdoMet production, keeping the intracellular AdoMet concentration at levels that are compatible with cell survival. This unexpected result, together with the fact that MAT activity and abundance changed with time in culture, suggests that different regulatory mechanisms acting beyond the post-transcriptional level are controlling this protein. In order to gain an insight into these mechanisms, several experiments were carried out to explain the MAT abundance during promastigote cell growth. Determination of MAT turnover in cycloheximide (CHX)-treated cultures resulted in a surprising 5-fold increase in MAT turnover compared to CHX-untreated cultures. This increase agrees with a stabilization of the MAT protein, whose integrity was maintained during culture. The presence of proteasome inhibitors, namely MG-132, MG-115, epoxomycin and lactacystin in the culture medium prevented MAT degradation in both MAT-overexpressing and 'mock-transfected' leishmanial strains. The role of the ubiquitin (Ub) pathway in MAT down-regulation was supported using immunoprecipitation experiments. Immunoprecipitated MAT cross-reacted with anti-Ub antibodies, which provides evidence of a proteasome-mediated down-regulation of the leishmanial MAT abundance.
机译：概述蛋氨酸腺苷基转移酶（MAT）是代谢过程中的重要酶，其程度是S-腺苷甲硫氨酸（AdoMet）在反甲基化，反硫化和多胺合成中起关键作用。先前的研究表明，过表达MAT的利什曼原虫（Leishmania donovani）菌株控制AdoMet的产生，将细胞内A​​doMet的浓度保持在与细胞存活率相适应的水平。这一出乎意料的结果，加上MAT的活性和丰度随着培养时间的变化而变化，这一事实表明，超出转录后水平的不同调控机制正在控制这种蛋白质。为了深入了解这些机制，进行了一些实验来解释前鞭毛体细胞生长过程中MAT的丰度。与未经CHX处理的培养物相比，用环己酰亚胺（CHX）处理的培养物测定MAT转换可导致MAT转换数惊人地增加5倍。这种增加与MAT蛋白的稳定相符，后者在培养过程中保持了完整性。培养基中蛋白酶体抑制剂MG-132，MG-115，环氧霉素和乳胞素的存在阻止了MAT过度表达和“模拟转染”的利什曼病菌株中的MAT降解。免疫沉淀实验支持泛素（Ub）通路在MAT下调中的作用。免疫沉淀的MAT与抗Ub抗体交叉反应，这提供了蛋白酶体介导的利什曼菌MAT丰度下调的证据。

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