A functional proteomics approach links the ubiquitin-related modifier Urm1 to a tRNA modification pathway
A functional proteomics approach links the ubiquitin-related modifier Urm1 to a tRNA modification pathway
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DOI：
10.1073/pnas.0808756105
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发表时间：
2008-11-25
影响因子：
11.1
通讯作者：
Ploegh, Hidde L.
中科院分区：
文献类型：
--
作者：
Schlieker, Christian D.;Van der Veen, Annemarthe G.;Ploegh, Hidde L.
Urm1是一种高度保守的功能未知的泛素相关修饰物。细胞Urm1水平的降低会导致HeLa细胞严重的胞质分裂缺陷，导致增大的多核细胞的聚集。为了了解潜在的机制，我们应用了功能蛋白质组学的方法，发现了一种将Urm1与tRNA修饰途径联系起来的酶活性。与泛素(Ub)和许多Ub样修饰物不同，Urm1通常连接到蛋白质靶标上，Urm1通过一种不寻常的机制激活，产生一种硫羧酸盐中间体，在tRNA硫化反应中充当硫供体。这一机制使人想起原核生物硫载体所使用的机制，从而定义了古老的Ub祖细胞和真核细胞的Ub/Ub样修饰系统之间的进化联系。
Urm1 is a highly conserved ubiquitin-related modifier of unknown function. A reduction of cellular Urm1 levels causes severe cytokinesis defects in HeLa cells, resulting in the accumulation of enlarged multinucleated cells. To understand the underlying mechanism, we applied a functional proteomics approach and discovered an enzymatic activity that links Urm1 to a tRNA modification pathway. Unlike ubiquitin (Ub) and many Ub-like modifiers, which are commonly conjugated to proteinaceous targets, Urm1 is activated by an unusual mechanism to yield a thiocarboxylate intermediate that serves as sulfur donor in tRNA thiolation reactions. This mechanism is reminiscent of that used by prokaryotic sulfur carriers and thus defines the evolutionary link between ancient Ub progenitors and the eukaryotic Ub/Ub-like modification systems.