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, Maarten
AU - Knipscheer, Puck
AU - Perrakis, Anastassis
AU - Blomen, Vincent A
AU - Brummelkamp, Thijn R
N1 - Copyright © 2017, American Association for the Advancement of Science.
PY - 2017/11/16
Y1 - 2017/11/16
N2 - Tubulin is subjected to a number of posttranslational modifications to generate heterogeneous microtubules. The modifications include removal and ligation of the carboxy-terminal tyrosine of ⍺-tubulin. Whereas enzymes for most modifications have been assigned, the enzymes responsible for detyrosination, an activity observed forty years ago, have remained elusive. We applied a haploid genetic screen 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 carboxy-terminal tyrosine of ⍺-tubulin. Vasohibins played a cell-type dependent role in detyrosination, but 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 carboxy-terminal tyrosine of ⍺-tubulin. Whereas enzymes for most modifications have been assigned, the enzymes responsible for detyrosination, an activity observed forty years ago, have remained elusive. We applied a haploid genetic screen 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 carboxy-terminal tyrosine of ⍺-tubulin. Vasohibins played a cell-type dependent role in detyrosination, but 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.
U2 - 10.1126/science.aao5676
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 -