β-subunit of nuclear pore-targeting complex (importin-β) can be exported from the nucleus in a Ran-independent manner

β-subunit of nuclear pore-targeting complex (importin-β) can be exported from the nucleus in a Ran-independent manner
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DOI:
10.1074/jbc.274.7.3946
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发表时间:
1999-02-12
影响因子:
4.8
通讯作者:
Yoneda, Y
Yoneda, Y
中科院分区:
生物学2区
文献类型:
--
作者:
Kose, S;Imamoto, N;Yoneda, Y

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importin-α的核输出是由GAS介导的,GAS与importin-β相关,而importin-β的输出机制仍不清楚。在本研究中,我们证明 importin-β 的核输出是由该分子的核孔复合物结合结构域介导的,对瘦霉素 B 不敏感表明其输出不是由富含亮氨酸的核输出信号特异性受体 CRM1 介导的。此外,与 GTPase 缺陷型 Ran 突变体 (G19V) 共注射不会抑制 importin-a 的核输出。细胞系 tsBN2 的 RCC1 基因中含有温度敏感点突变,该基因编码 Ran 的鸟嘌呤核苷酸交换因子。在不允许的温度下,即使同时注射 Ran-GAP1(Ran 的 GTP 酶激活蛋白),importin-β 也会从这些细胞的细胞核中输出。这些结果不仅支持了Importin-β的核输出不需要Ran依赖性GTP水解的观点,而且表明核RanGTP对其输出不是必需的。因此,我们提出:importin-beta 可以以独立于 Ran 的方式单独从细胞核中回收。
The nuclear export of importin-alpha is mediated by GAS, which is related to importin-beta, whereas the mechanism for the export of importin-beta remains unclear. In this study, we demonstrate that the nuclear export of importin-beta is mediated by the nuclear pore complex-binding domain of this molecule, Insensitivity to leptomycin B indicates that its export is not mediated by a leucine-rich nuclear export signal-specific receptor, CRM1. Furthermore, the nuclear export of importin-a was not inhibited by co-injection with a GTPase-deficient Ran mutant (G19V), The cell line tsBN2 contains a temperature-sensitive point mutation in the RCC1 gene, which encodes a guanine nucleotide exchange factor of Ran. At the nonpermissive temperature, importin-beta was exported from the nucleus of these cells, even when Ran-GAP1, a GTPase-activating protein for Ran, was co-injected. These results not only provide support for the view that Ran-dependent GTP hydrolysis is not required for the nuclear export of importin-beta but also indicate that nuclear RanGTP is not essential for its export. As a result, we propose: that importin-beta can be recycled from the nucleus alone in a Ran-independent manner.