The Survivin-Crm1 interaction is essential for chromosomal passenger complex localization and function
The Survivin-Crm1 interaction is essential for chromosomal passenger complex localization and function
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DOI：
10.1038/sj.embor.7400824
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发表时间：
2006-12-01
期刊：
影响因子：
7.7
通讯作者：
Stauber, Roland H.
中科院分区：
文献类型：
--
作者：
Knauer, Shirley K.;Bier, Carolin;Stauber, Roland H.
Aurora-B、Borealin、INCENP（内着丝粒蛋白）和Survivin的染色体乘客复合物（CPC）协调有丝分裂期间的基本染色体和细胞骨架事件。在这里，我们表明，核输出受体Crm 1是至关重要的参与拴系CPC的着丝粒通过相互作用与亮氨酸丰富的核输出信号（内斯），进化上保守的所有哺乳动物生存蛋白。我们发现，抑制Survivin-Crm 1相互作用的治疗与链霉素B或RNA干扰介导的Crm 1耗尽阻止着丝粒靶向的Survivin。通过内斯的突变使Survivin-Crm 1相互作用的遗传失活影响Survivin和CPC在有丝分裂期间的正确定位和功能。相比之下，CPC组装似乎不需要Survivin-Crm 1相互作用。我们的报告显示了Survivin-Crm 1接口的功能意义，并提供了一个新的有丝分裂效应器Crm 1和CPC之间的联系。
The chromosomal passenger complex (CPC) of Aurora-B, Borealin, INCENP (inner centromere protein) and Survivin coordinates essential chromosomal and cytoskeletal events during mitosis. Here, we show that the nuclear export receptor Crm1 is crucially involved in tethering the CPC to the centromere by interacting with a leucine-rich nuclear export signal (NES), evolutionarily conserved in all mammalian Survivin proteins. We show that inhibition of the Survivin-Crm1 interaction by treatment with leptomycin B or by RNA-interference-mediated Crm1 depletion prevents centromeric targeting of Survivin. The genetic inactivation of the Survivin-Crm1 interaction by mutation of the NES affects the correct localization and function of Survivin and the CPC during mitosis. By contrast, CPC assembly does not seem to require the Survivin-Crm1 interaction. Our report shows the functional significance of the Survivin-Crm1 interface and provides a novel link between the mitotic effector Crm1 and the CPC.