Vasohibins encode tubulin detyrosinating activity
Vasohibins encode tubulin detyrosinating activity
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DOI：
10.1126/science.aao5676
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发表时间：
2017-12-15
期刊：
影响因子：
56.9
通讯作者：
Brummelkamp, Thijn R.
中科院分区：
文献类型：
--
作者：
Nieuwenhuis, Joppe;Adamopoulos, Athanassios;Brummelkamp, Thijn R.
微管蛋白受到许多翻译后修饰以产生不均匀的微管。修饰包括去除和连接α -微管蛋白的c端酪氨酸。负责去酪氨酸的酶，一种40年前首次观察到的活动，仍然难以捉摸。我们在单倍体人类细胞中应用基因筛选来寻找微管蛋白去酪氨酸的调节因子。我们确定了SVBP，一种调节血管泌素（VASH1和VASH2）丰度的肽。血管球蛋白，而不是单独的SVBP，增加了α -微管蛋白的去酪氨酸，纯化的血管球蛋白去除了α -微管蛋白的c端酪氨酸。我们发现vasohibin在去酪氨酸中发挥细胞类型依赖的作用，尽管细胞也含有额外的去酪氨酸活性。因此，血管新生蛋白，迄今为止研究的作为分泌血管生成调节剂，构成了微管蛋白酪氨酸化周期中寻找已久的缺失环节。
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 alpha-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 alpha-tubulin, and purified vasohibins removed the C-terminal tyrosine of alpha-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.