Fornerod M, van Deursen J, van Baal S, Reynolds A, Davis D, Murti K G, Fransen J, Grosveld G
Department of Genetics, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
EMBO J. 1997 Feb 17;16(4):807-16. doi: 10.1093/emboj/16.4.807.
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.
致癌核孔蛋白CAN/Nup214在脊椎动物细胞中至关重要。其缺失会导致核蛋白输入缺陷、信使核糖核酸输出受抑制以及细胞周期停滞。我们最近发现CAN与88 kDa和112 kDa的蛋白质相关联，我们现已对其进行克隆和表征。88 kDa的蛋白质是一种新型核孔复合体（NPC）成分，我们将其命名为Nup88。从NPC中去除CAN会导致Nup88随之丢失，这表明Nup88在NPC上的定位依赖于CAN结合。112 kDa的蛋白质是酵母CRM1的人类同源物，已知该蛋白质是维持正确染色体结构所必需的。这种人类CRM1（hCRM1）定位于NPC以及核质中。CAN的FG重复区域（包含其与hCRM1相互作用的结构域）在细胞核中过表达，导致hCRM1从NPC中耗尽。在缺乏CAN的CAN-/-小鼠胚胎中，hCRM1保留在核膜中，这表明该蛋白质也可以与其他含重复序列的核孔蛋白结合。最后，hCRM1与importin-β有一个显著同源的结构域，importin-β是一种与核孔蛋白重复区域相互作用的细胞质转运因子。我们提出hCRM1是一种与NPC相互作用的可溶性核转运因子。
