Inhibition of tumor angiogenesis by a natural fragment of a tRNA synthetase

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use*
  • Humans
  • Neoplasms / blood supply*
  • Neovascularization, Pathologic / prevention & control*
  • Peptide Fragments / therapeutic use*
  • Tryptophan-tRNA Ligase / therapeutic use*
  • Tyrosine-tRNA Ligase / therapeutic use*


  • Angiogenesis Inhibitors
  • Peptide Fragments
  • Tyrosine-tRNA Ligase
  • Tryptophan-tRNA Ligase