Tzima Ellie, Schimmel Paul
Skaggs Institute for Chemical Biology, Departments of Chemistry and Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Trends Biochem Sci. 2006 Jan;31(1):7-10. doi: 10.1016/j.tibs.2005.11.002. Epub 2005 Nov 16.
Human tyrosyl- and tryptophanyl-tRNA synthetases (TyrRS and TrpRS, respectively) link protein synthesis to signal-transduction pathways, including angiogenesis. Fragments of TyrRS stimulate angiogenesis, whereas those of TrpRS (T2-TrpRS) inhibit angiogenesis. Thus, these two synthetases acquired opposing activities during evolution, possibly as a coordinated mechanism for regulating angiogenesis. The recent identification of the cellular target of T2-TrpRS sheds light into the mechanism of angiogenesis inhibition. This mechanism provides a molecular basis for the lack of effect of T2-TrpRS on the normal vasculature. With these features, we suggest that this fragment of a tRNA synthetase might safely be used to arrest neovascularization of tumors. In particular, an anti-angiogenesis agent that stops the growth of tumor vessels without affecting normal vessels might serve as an adjunct to cytotoxic therapy.
人类酪氨酰 - 和色氨酰 - tRNA合成酶（分别为TyrRS和TrpRS）将蛋白质合成与信号转导途径联系起来，包括血管生成。TyrRS的片段刺激血管生成，而TrpRS的片段（T2-TrpRS）抑制血管生成。因此，这两种合成酶在进化过程中获得了相反的活性，可能是作为调节血管生成的一种协调机制。最近对T2-TrpRS细胞靶点的鉴定揭示了血管生成抑制的机制。这种机制为T2-TrpRS对正常脉管系统无影响提供了分子基础。基于这些特性，我们认为这种tRNA合成酶的片段可能安全地用于阻止肿瘤的新生血管形成。特别是，一种能阻止肿瘤血管生长而不影响正常血管的抗血管生成剂可能作为细胞毒性疗法的辅助手段。
