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一种抗癌的S-腺苷同型半胱氨酸(SAH)类似物:5'-脱氧5'-S-异丁基腺苷(SIBA)对体外和全细胞中tRNA甲基化的抑制作用。

Inhibition of tRNA methylation in vitro and in whole cells by an oncostatic S-adenosyl-homocysteine (SAH) analogue: 5'-deoxy 5'-S-isobutyl adenosine (SIBA).

作者信息

Vedel M, Robert-Géro M, Legraverend M, Lawrence F, Lederer E

出版信息

Nucleic Acids Res. 1978 Aug;5(8):2979-89. doi: 10.1093/nar/5.8.2979.

Abstract

A high increase in the amount of methylated tRNA bases was found in vivo in Rous sarcoma virus infected and transformed chick embryo fibroblasts in comparison with normal cells, tRNA methylases extracted from transformed cells showed also higher activity in vitro with a heterologous substrate. 5'-deoxy-5'-S-isobutyl adenosine, (a structural analogue of S-adenosyl-L homocysteine), which inhibits virus-induced cell transformation, inhibits also the increase of incorporation of labelled methyl groups into tRNA in infected and transformed cells. When normal cells are grown in the presence of this inhibitor, undermethylated tRNAs are obtained. The effect of the drug is different in normal, infected and transformed cells. The methylation of the different bases is inhibited in vitro and in vivo to various extent. The effect of this substance on tRNA methylation may be the cause of its inhibitory effect on cell transformation.

摘要

与正常细胞相比,在劳斯肉瘤病毒感染并转化的鸡胚成纤维细胞中发现,体内甲基化的tRNA碱基量有显著增加。从转化细胞中提取的tRNA甲基化酶在体外对异源底物也表现出更高的活性。5'-脱氧-5'-S-异丁基腺苷(S-腺苷-L-高半胱氨酸的结构类似物)可抑制病毒诱导的细胞转化,同时也抑制感染和转化细胞中标记甲基掺入tRNA的增加。当正常细胞在这种抑制剂存在的情况下生长时,会得到甲基化不足的tRNA。该药物对正常细胞、感染细胞和转化细胞的作用不同。不同碱基的甲基化在体外和体内受到不同程度的抑制。这种物质对tRNA甲基化的影响可能是其对细胞转化产生抑制作用的原因。

相似文献

5
Effects of 5'deoxy-5'-methylthioadenosine on the metabolism of S-adenosyl methionine.
Biochem Biophys Res Commun. 1983 Jul 18;114(1):214-21. doi: 10.1016/0006-291x(83)91615-7.

本文引用的文献

6
Studies on inhibitors of mammalian tRNA methylases.哺乳动物tRNA甲基化酶抑制剂的研究。
FEBS Lett. 1971 Jul 15;16(1):13-16. doi: 10.1016/0014-5793(71)80672-5.

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