A novel class of RanGTP binding proteins.
A novel class of RanGTP binding proteins.
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DOI：
10.1083/jcb.138.1.65
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发表时间：
1997-07-14
期刊：
影响因子：
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通讯作者：
Izaurralde E
中科院分区：
文献类型：
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作者：
Görlich D;Dabrowski M;Bischoff FR;Kutay U;Bork P;Hartmann E;Prehn S;Izaurralde E
importin-α/β复合物和GTPase Ran通过经典的核定位信号介导蛋白质的核输入。尽管Ran也参与了许多其他过程，如细胞周期进程，但Ran的直接功能迄今为止仅被证明用于输入蛋白介导的核输入。我们现在已经确定了一整类1020个潜在的Ran靶标，它们共享与输入蛋白-β的Ran结合位点相关的序列基序。我们已经证实了其中一些特定的RanGTP结合，即两个新的因素，RanBP 7和RanBP 8，CAS，Pse 1 p和Msn 5 p，和细胞周期调节Cse 1 p从酿酒酵母。我们更详细地研究了RanBP 7。与importin-β类似，它阻止RanGAP 1激活Ran's GTP酶并抑制RanGTP上的核苷酸交换。RanBP 7直接与核孔复合物结合，在那里它与输入蛋白-β、转运蛋白竞争结合位点，显然还与mRNA和U snRNA输出的介体竞争结合位点。此外，我们提供的证据RanBP 7的RAN依赖的运输周期，并证明RanBP 7可以跨越核膜迅速和在两个方向。在这些结果的基础上，我们提出RanBP 7可能代表了一种携带未知货物的核转运因子，这也适用于这一类相关的RanGTP结合蛋白。
The importin-α/β complex and the GTPase Ran mediate nuclear import of proteins with a classical nuclear localization signal. Although Ran has been implicated also in a variety of other processes, such as cell cycle progression, a direct function of Ran has so far only been demonstrated for importin-mediated nuclear import. We have now identified an entire class of ∼20 potential Ran targets that share a sequence motif related to the Ran-binding site of importin-β. We have confirmed specific RanGTP binding for some of them, namely for two novel factors, RanBP7 and RanBP8, for CAS, Pse1p, and Msn5p, and for the cell cycle regulator Cse1p from Saccharomyces cerevisiae. We have studied RanBP7 in more detail. Similar to importin-β, it prevents the activation of Ran's GTPase by RanGAP1 and inhibits nucleotide exchange on RanGTP. RanBP7 binds directly to nuclear pore complexes where it competes for binding sites with importin-β, transportin, and apparently also with the mediators of mRNA and U snRNA export. Furthermore, we provide evidence for a Ran-dependent transport cycle of RanBP7 and demonstrate that RanBP7 can cross the nuclear envelope rapidly and in both directions. On the basis of these results, we propose that RanBP7 might represent a nuclear transport factor that carries an as yet unknown cargo, which could apply as well for this entire class of related RanGTP-binding proteins.