An efficient mammalian transfer RNA target for bleomycin
An efficient mammalian transfer RNA target for bleomycin
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DOI：
10.1021/ja066187x
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发表时间：
2006-11-22
影响因子：
15
通讯作者：
Hecht, Sidney M.
中科院分区：
文献类型：
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作者：
Tao, Zhi-Fu;Konishi, Kazuhide;Hecht, Sidney M.
长期以来，抗肿瘤抗生素博来霉素一直被认为是在 DNA 裂解水平上发挥其治疗作用。最近，有证据表明 RNA 切割也可能很重要，并且可能涉及一种或多种转移 RNA。为了定义那些可能代表博莱霉素作用的重要位点的 tRNA，我们分离了鸡肝 tRNA，并鉴定了最容易受到 Fe(II)·BLM 氧化裂解的同工受体。两个鸡肝 tRNA（tRNA3Lys 和 tRNAPhe）被发现能够被 Fe(II)·BLM 非常方便地切割，并且两者都主要在 U66 处切割。结果表明，tRNA3Lys 的裂解受 Mg2+ 生理浓度的影响最小。鸡肝 tRNA3Lysis 与人 tRNA3Lys 序列相同。这些发现支持关键 tRNA（例如 tRNA3Lysin）在博莱霉素介导其抗肿瘤活性的机制中可能发挥的作用。
The antitumor antibiotic bleomycin has long been believed to exert its therapeutic effects at the level of DNA cleavage. Recently, evidence has been presented to suggest that RNA cleavage may also be important and that one or more transfer RNAs may be involved. To define those tRNAs that may represent important loci for the action of bleomycin, we have fractionated chicken liver tRNAs and identified those isoacceptors most susceptible to oxidative cleavage by Fe(II)·BLM. Two chicken liver tRNAs, tRNA3Lysand tRNAPhe, were found to be cleaved with exceptional facility by Fe(II)·BLM, and both were cleaved predominantly at U66. The cleavage of tRNA3Lyswas shown to be minimally affected by physiological concentrations of Mg2+. Chicken liver tRNA3Lysis identical in sequence with human tRNA3Lys. These findings support a possible role for a critical tRNA such as tRNA3Lysin the mechanism by which bleomycin mediates its antitumor activity.