Vasohibins encode tubulin detyrosinating activity

Joppe Nieuwenhuis; Athanassios Adamopoulos; Onno B Bleijerveld; Abdelghani Mazouzi; Elmer Stickel; Patrick Celie; Maarten Altelaar; Puck Knipscheer; Anastassis Perrakis; Vincent A Blomen; Thijn R Brummelkamp

doi:10.1126/science.aao5676

Vasohibins encode tubulin detyrosinating activity

Joppe Nieuwenhuis, Athanassios Adamopoulos, Onno B Bleijerveld, Abdelghani Mazouzi, Elmer Stickel, Patrick Celie, Maarten Altelaar, Puck Knipscheer, Anastassis Perrakis, Vincent A Blomen, Thijn R Brummelkamp

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

169 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1453-1456
Number of pages	4
Journal	Science
Volume	358
Issue number	6369
DOIs	https://doi.org/10.1126/science.aao5676
Publication status	Published - 15 Dec 2017

Keywords

Journal Article
Research Support, Non-U.S. Gov't

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title = "Vasohibins encode tubulin detyrosinating activity",

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.",

keywords = "Journal Article, Research Support, Non-U.S. Gov't",

author = "Joppe Nieuwenhuis and Athanassios Adamopoulos and Bleijerveld, {Onno B} and Abdelghani Mazouzi and Elmer Stickel and Patrick Celie and Maarten Altelaar and Puck Knipscheer and Anastassis Perrakis and Blomen, {Vincent A} and Brummelkamp, {Thijn R}",

note = "Copyright {\textcopyright} 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.",

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doi = "10.1126/science.aao5676",

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T1 - Vasohibins encode tubulin detyrosinating activity

AU - Nieuwenhuis, Joppe

AU - Adamopoulos, Athanassios

AU - Bleijerveld, Onno B

AU - Mazouzi, Abdelghani

AU - Stickel, Elmer

AU - Celie, Patrick

AU - Altelaar, Maarten

AU - Knipscheer, Puck

AU - Perrakis, Anastassis

AU - Blomen, Vincent A

AU - Brummelkamp, Thijn R

PY - 2017/12/15

Y1 - 2017/12/15

N2 - 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.

AB - 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.

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

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DO - 10.1126/science.aao5676

M3 - Article

C2 - 29146869

SN - 0036-8075

VL - 358

SP - 1453

EP - 1456

JO - Science

JF - Science

IS - 6369

ER -

Vasohibins encode tubulin detyrosinating activity

Abstract

Keywords

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