Vasohibins encode tubulin detyrosinating activity

Science. 2017 Dec 15;358(6369):1453-1456. doi: 10.1126/science.aao5676. Epub 2017 Nov 16.


Tubulin is subjected to a number of posttranslational modifications to generate heterogeneous microtubules. The modifications include removal and ligation of the C-terminal tyrosine of ⍺-tubulin. The enzymes responsible for detyrosination, an activity first observed 40 years ago, have remained elusive. We applied a genetic screen in haploid human cells to find regulators of tubulin detyrosination. We identified SVBP, a peptide that regulates the abundance of vasohibins (VASH1 and VASH2). Vasohibins, but not SVBP alone, increased detyrosination of ⍺-tubulin, and purified vasohibins removed the C-terminal tyrosine of ⍺-tubulin. We found that vasohibins play a cell type-dependent role in detyrosination, although cells also contain an additional detyrosinating activity. Thus, vasohibins, hitherto studied as secreted angiogenesis regulators, constitute a long-sought missing link in the tubulin tyrosination cycle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenic Proteins / genetics
  • Angiogenic Proteins / metabolism*
  • Biocatalysis
  • Carboxypeptidases / genetics
  • Carboxypeptidases / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Haploidy
  • Humans
  • Neovascularization, Physiologic
  • Tubulin / metabolism*
  • Tyrosine / metabolism*


  • Angiogenic Proteins
  • Carrier Proteins
  • Cell Cycle Proteins
  • SVBP protein, human
  • Tubulin
  • VASH1 protein, human
  • VASH2 protein, human
  • Tyrosine
  • Carboxypeptidases
  • tyrosyltubulin carboxypeptidase