2. Academic Validation
  3. Vasohibins encode tubulin detyrosinating activity

Vasohibins encode tubulin detyrosinating activity

  • Science. 2017 Dec 15;358(6369):1453-1456. doi: 10.1126/science.aao5676.
Joppe Nieuwenhuis 1,  Athanassios Adamopoulos 1,  Onno B Bleijerveld 1,  Abdelghani Mazouzi 1,  Elmer Stickel 1,  Patrick Celie 1,  Maarten Altelaar 1 2,  Puck Knipscheer 3 4,  Anastassis Perrakis 1,  Vincent A Blomen 5,  Thijn R Brummelkamp 5 4 6
Affiliations

Affiliations

  • 1 Division of Biochemistry, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, Netherlands.
  • 2 Biomolecular Mass Spectrometry and Proteomics, Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, 3584 CH Utrecht, Netherlands.
  • 3 Hubrecht Institute-KNAW, University Medical Center Utrecht, 3584 CT Utrecht, Netherlands.
  • 4 CGC.nl, Plesmanlaan 121, 1066 CX Amsterdam, Netherlands.
  • 5 Division of Biochemistry, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, Netherlands. vincent.blomen@scenicbiotech.com t.brummelkamp@nki.nl.
  • 6 CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.
PMID: 29146869 DOI: 10.1126/science.aao5676
Abstract

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.

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