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

Vasohibins encode tubulin detyrosinating activity.

Author information

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.

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.

PMID:
29146869
DOI:
10.1126/science.aao5676
[Indexed for MEDLINE]

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