Usp39 is essential for mitotic spindle checkpoint integrity and controls mRNA-levels of aurora B
Usp39 is essential for mitotic spindle checkpoint integrity and controls mRNA-levels of aurora B
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DOI：
10.4161/cc.7.17.6553
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发表时间：
2008-09-01
期刊：
影响因子：
4.3
通讯作者：
Medema, Rene H.
中科院分区：
文献类型：
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作者：
van Leuken, Renske J.;Luna-Vargas, Mark P.;Medema, Rene H.
准确的染色体分离依赖于有丝分裂纺锤体检查点。该检查点的作用是限制有丝分裂中后期促进复合物 (APC/C) 的泛素连接酶活性，直到所有染色体双极附着在有丝分裂纺锤体上。我们进行了基于功能性 RNAi 的筛选，以确定参与有丝分裂进展的去泛素化酶 (Dubs)。我们确定 Usp39 是维持纺锤体检查点和支持成功胞质分裂所需的新因子。引人注目的是，尽管 Usp39 明显包含泛素蛋白酶结构域，但我们发现 Usp39 完全缺乏 Dub 活性。然而，与之前描述的 Usp39 在 mRNA 加工中的作用一致，我们观察到 Usp39 耗尽后 Aurora B-mRNA 水平出现特异性降低。尽管我们发现外源表达的 Aurora B cDNA 不足以挽救 Usp39 耗尽细胞的检查点缺陷，但 Aurora B 表达已恢复。我们的观察表明，Usp39 参与 Aurora B 和其他 mRNA 的剪接，这对于纺锤体检查点的正常功能至关重要。
Accurate chromosome segregation relies on the mitotic spindle checkpoint. This checkpoint acts to restrict ubiquitin ligase activity of the Anaphase-promoting complex (APC/C) in mitosis until all chromosomes are bipolarly attached to the mitotic spindle. We performed a functional RNAi-based screen to identify De-ubiquitinating enzymes (Dubs) involved in mitotic progression. We identified Usp39 as a new factor required to maintain the spindle checkpoint and support successful cytokinesis. Strikingly, although Usp39 clearly contains an ubiquitin-protease domain, we show that Usp39 is entirely deprived of Dub activity. However, consistent wilt a previously described role for Usp39 in mRNA processing, we observed specific reduction in Aurora B-mRNA levels after depletion of Usp39. Although we find that exogenously expressed Aurora B cDNA is not sufficient to rescue the checkpoint defect of Usp39-depleted cells, Aurora B expression is restored. Our observations suggest Usp39 to be involved in splicing of Aurora B and other mRNAs that are essential for proper spindle checkpoint function.