The mobile FG nucleoporin Nup98 is a cofactor for Crm1-dependent protein export.

The mobile FG nucleoporin Nup98 is a cofactor for Crm1-dependent protein export.
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DOI:
10.1091/mbc.e09-12-1041
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发表时间:
2010-06-01
影响因子:
3.3
通讯作者:
Yoneda Y
Yoneda Y
中科院分区:
生物学3区
文献类型:
--
作者:
Oka M;Asally M;Yasuda Y;Ogawa Y;Tachibana T;Yoneda Y

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Nup98是一种可移动的核孔蛋白,在细胞核中形成不同的点。我们的研究结果表明,Nup98在crm1介导的核输出中起着新的穿梭辅因子的作用。Nup98是一种可移动的核孔蛋白,在细胞核中形成不同的点,尽管Nup98在核运输中的作用已被提出,但其确切功能尚不清楚。在这里,我们发现Nup98在crm1介导的核蛋白输出中起重要作用。用leptomycin B(一种核输出受体Crm1的特异性抑制剂)处理后,细胞核而非细胞质中egfp标记的Nup98点迅速消失。突变分析表明,Nup98在物理和功能上通过其n端苯丙氨酸-甘氨酸(FG)重复区以依赖于rangtp的方式与Crm1相互作用。此外,Nup98-Crm1复合物的活性由RanBP3调节,RanBP3是已知的crm1介导的核输出的辅助因子。最后,胞质微注射抗nup98抑制了crm1依赖的细胞核蛋白输出,同时在细胞核中积累了抗nup98。这些结果清楚地表明,Nup98与RanBP3一起作为crm1介导的核输出的新型穿梭辅因子发挥作用。
Nup98 is a mobile nucleoporin that forms distinct dots in the nucleus. Our results show that Nup98 functions as a novel shuttling cofactor in Crm1-mediated nuclear export. Nup98 is a mobile nucleoporin that forms distinct dots in the nucleus, and, although a role for Nup98 in nuclear transport has been suggested, its precise function remains unclear. Here, we show that Nup98 plays an important role in Crm1-mediated nuclear protein export. Nuclear, but not cytoplasmic, dots of EGFP-tagged Nup98 disappeared rapidly after cell treatment with leptomycin B, a specific inhibitor of the nuclear export receptor, Crm1. Mutational analysis demonstrated that Nup98 physically and functionally interacts with Crm1 in a RanGTP-dependent manner through its N-terminal phenylalanine-glycine (FG) repeat region. Moreover, the activity of the Nup98-Crm1 complex was modulated by RanBP3, a known cofactor for Crm1-mediated nuclear export. Finally, cytoplasmic microinjection of anti-Nup98 inhibited the Crm1-dependent nuclear export of proteins, concomitant with the accumulation of anti-Nup98 in the nucleus. These results clearly demonstrate that Nup98 functions as a novel shuttling cofactor for Crm1-mediated nuclear export in conjunction with RanBP3.
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发表时间: 2005-12-05
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