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The Survivin–Crm1 interaction is essential for chromosomal passenger complex localization and function

机译:Survivin–Crm1相互作用对于染色体乘客复合体的定位和功能至关重要

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摘要

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.
机译:Aurora-B,Borealin,INCENTP(内部着丝粒蛋白)和Survivin的染色体乘客复合物(CPC)协调有丝分裂过程中必需的染色体和细胞骨架事件。在这里,我们显示核出口受体Crm1通过与富含哺乳动物亮氨酸的核出口信号(NES)相互作用而在将CPC束缚在着丝粒上至关重要,该信号在所有哺乳动物Survivin蛋白中均在进化上保守。我们显示,通过用细霉素B或RNA干扰介导的Crm1耗竭治疗抑制Survivin-Crm1相互作用可防止着丝粒靶向Survivin。 NES突变导致Survivin-Crm1相互作用的遗传失活会影响有丝分裂期间Survivin和CPC的正确定位和功能。相比之下,CPC组装似乎不需要Survivin-Crm1相互作用。我们的报告显示了Survivin–Crm1界面的功能意义,并提供了有丝分裂效应器Crm1和CPC之间的新型链接。

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