TY - JOUR
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, A. F Maarten
AU - Knipscheer, Puck
AU - Perrakis, Anastassis
AU - Blomen, Vincent A.
AU - Brummelkamp, Thijn R.
N1 - Funding Information:
We thank R. Medema, J. van den Berg, H. Janssen, and members of the Brummelkamp laboratory for discussions; A. Fish for advice in performing biochemical assays; M. Stadnik-Spiewak for assisting in protein expression experiments; D. Peeper for CHL-1 cells; and T. Sixma for carefully reading the manuscript. Supported by NWO Vici Grant 016.Vici.170.033, KWF grant NKI2015-7609, the Cancer Genomics Center (CGC.nl), and the Ammodo KNAW Award 2015 for Biomedical Sciences (T.R.B.); the Netherlands Organization for Scientific Research (NWO) as part of the National Roadmap Large-scale Research Facilities of the Netherlands, Proteins@Work project number 184.032.201 (O.B.B. and M.A.); and VIDI grant 723.012.102 (M.A.). The HAP1 cell line is available from T.R.B. under a material transfer agreement with the Netherlands Cancer Institute. Sequencing data have been deposited in the NCBI Sequence Read Archive (www.ncbi.nlm.nih.gov.sra) under accession number SRP119153. Processed screen results are accessible in an interactive database (https://phenosaurus.nki.nl/).
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 - Angiogenic Proteins
KW - Biocatalysis
KW - Carboxypeptidases
KW - Carrier Proteins
KW - Cell Cycle Proteins
KW - Haploidy
KW - Humans
KW - Neovascularization, Physiologic
KW - Tubulin
KW - Tyrosine
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
UR - https://www.scopus.com/pages/publications/85034439895
U2 - 10.1126/science.aao5676
DO - 10.1126/science.aao5676
M3 - Article
C2 - 29146869
AN - SCOPUS:85034439895
SN - 0036-8075
VL - 358
SP - 1453
EP - 1456
JO - Science
JF - Science
IS - 6369
ER -