The human homologue of yeast CRM1 is in a dynamic subcomplex with CAN/Nup214 and a novel nuclear pore component Nup88
The human homologue of yeast CRM1 is in a dynamic subcomplex with CAN/Nup214 and a novel nuclear pore component Nup88
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DOI：
10.1093/emboj/16.4.807
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发表时间：
1997-02-17
期刊：
影响因子：
11.4
通讯作者：
Grosveld, G
中科院分区：
文献类型：
--
作者：
Fornerod, M;vanDeursen, J;Grosveld, G
致癌核孔蛋白CAN/Nup 214在脊椎动物细胞中是必需的。它的消耗导致有缺陷的核蛋白输入，抑制信使RNA输出和细胞周期停滞。我们最近发现，CAN协会与88和112 kDa的蛋白质，我们现在已经克隆和表征。88 kDa蛋白是一种新的核孔复合物（NPC）组分，我们将其命名为Nup 88。CAN从NPC的消耗导致Nup 88的伴随损失，表明Nup 88到NPC的定位依赖于CAN结合。112 kDa蛋白是酵母CRM 1的人类同源物，酵母CRM 1是已知维持正确染色体结构所需的蛋白质。这种人CRM 1（hCRM 1）定位于NPC以及核质。CAN的FG-重复区域的核过表达，包含其hCRM 1相互作用结构域，导致hCRM 1从NPC中耗尽。在缺乏CAN的CAN-/-小鼠胚胎中，hCRM 1保留在核膜中，表明这种蛋白质也可以与其他含有重复序列的核孔蛋白结合。最后，hCRM 1与importin-β（一种与核孔蛋白重复区相互作用的细胞质转运因子）共享一个具有显著同源性的结构域。我们认为hCRM 1是一种可溶性核转运因子，与NPC相互作用。
The oncogenic nucleoporin CAN/Nup214 is essential in vertebrate cells. Its depletion results in defective nuclear protein import, inhibition of messenger RNA export and cell cycle arrest. We recently found that CAN associates with proteins of 88 and 112 kDa, which we have now cloned and characterized. The 88 kDa protein is a novel nuclear pore complex (NPC) component, which we have named Nup88. Depletion of CAN from the NPC results in concomitant loss of Nup88, indicating that the localization of Nup88 to the NPC is dependent on CAN binding. The 112 kDa protein is the human homologue of yeast CRM1, a protein known to be required for maintenance of correct chromosome structure. This human CRM1 (hCRM1) localized to the NPC as well as to the nucleoplasm. Nuclear overexpression of the FG-repeat region of CAN, containing its hCRM1-interaction domain, resulted in depletion of hCRM1 from the NPC. In CAN-/- mouse embryos lacking CAN, hCRM1 remained in the nuclear envelope, suggesting that this protein can also bind to other repeat-containing nucleoporins. Lastly, hCRM1 shares a domain of significant homology with importin-beta, a cytoplasmic transport factor that interacts with nucleoporin repeat regions. We propose that hCRM1 is a soluble nuclear transport factor that interacts with the NPC.