Ran-binding protein 3 is a cofactor for Crm1-mediated nuclear protein export.

Ran-binding protein 3 is a cofactor for Crm1-mediated nuclear protein export.
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DOI:
10.1083/jcb.153.7.1391
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发表时间:
2001-06-25
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Macara IG
Macara IG
中科院分区:
其他
文献类型:
--
作者:
Lindsay ME;Holaska JM;Welch K;Paschal BM;Macara IG

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Crm 1是核浆转运受体的核浆转运蛋白家族的成员,通过与货物和Ran:GTP形成三元复合物介导蛋白质从细胞核的输出。该复合物通过核孔移位并在胞质溶胶中解离。酵母蛋白Yrb 2 p参与该途径并结合Crm 1,但其作用机制尚未确定。我们发现,人类直系同源的Yrb 2 p,RAN结合蛋白3(RanBP 3),作为一个辅因子Crm 1介导的出口透化细胞测定。RanBP 3直接结合Crm 1,复合物对Ran:GTP和货物都具有增强的亲和力。RanBP 3通过Crm 1依赖的机制穿梭于细胞核和细胞质之间,Crm 1-RanBP 3-NES-Ran:GTP四元复合物可与核孔蛋白结合。我们推断,这个复杂的易位通过核孔的细胞质中,它是由RanBP 1和Ran GTP酶激活蛋白分解。
Crm1 is a member of the karyopherin family of nucleocytoplasmic transport receptors and mediates the export of proteins from the nucleus by forming a ternary complex with cargo and Ran:GTP. This complex translocates through the nuclear pores and dissociates in the cytosol. The yeast protein Yrb2p participates in this pathway and binds Crm1, but its mechanism of action has not been established. We show that the human orthologue of Yrb2p, Ran-binding protein 3 (RanBP3), acts as a cofactor for Crm1-mediated export in a permeabilized cell assay. RanBP3 binds directly to Crm1, and the complex posseses an enhanced affinity for both Ran:GTP and cargo. RanBP3 shuttles between the nucleus and the cytoplasm by a Crm1-dependent mechanism, and the Crm1–RanBP3-NES-Ran:GTP quarternary complex can associate with nucleoporins. We infer that this complex translocates through the nuclear pore to the cytoplasm where it is disassembled by RanBP1 and Ran GTPase–activating protein.
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