Nuclear import of the ran exchange factor, RCC1, is mediated by at least two distinct mechanisms.
Nuclear import of the ran exchange factor, RCC1, is mediated by at least two distinct mechanisms.
复制标题
RAN交换因子RCC1的核进口至少由两种不同的机制介导。
DOI：
10.1083/jcb.149.4.835
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发表时间：
2000-05-15
影响因子：
7.8
通讯作者：
Macara, I G
中科院分区：
文献类型：
--
作者：
Nemergut, M E;Macara, I G
RCC 1是Ran GTdR的唯一已知的鸟嘌呤核苷酸交换因子，是一种能结合染色质的分子量为45 kD的核蛋白。一个重要的问题是RCC 1如何穿过核膜。我们现在表明，核RCC 1是不容易出口间期细胞和进口的RCC 1到核质是非常迅速的。导入可以通过至少两种不同的机制进行。第一种是由RCC 1的NH 2-末端结构域（NTD）内的碱性残基介导的经典输入途径。该途径依赖于预先存在的Ran梯度和能量，并且优先使用输入蛋白-α的输入蛋白-α3同种型。第二条途径不受RCC 1的NTD介导。这种新的途径不需要输入蛋白-α或输入蛋白-β或任何其他可溶性因子的体外添加;然而，这种途径是饱和的，并且仅对经典输入途径的抑制剂的子集敏感。此外，RCC 1的核输入不需要预先存在的Ran梯度或能量。我们推测，这第二个输入途径的演变，以确保RCC 1永远不会在细胞质中积累。
RCC1, the only known guanine-nucleotide exchange factor for the Ran GTPase, is an ∼45-kD nuclear protein that can bind chromatin. An important question concerns how RCC1 traverses the nuclear envelope. We now show that nuclear RCC1 is not exported readily in interphase cells and that the import of RCC1 into the nucleoplasm is extremely rapid. Import can proceed by at least two distinct mechanisms. The first is a classic import pathway mediated by basic residues within the NH2-terminal domain (NTD) of RCC1. This pathway is dependent upon both a preexisting Ran gradient and energy, and preferentially uses the importin-α3 isoform of importin-α. The second pathway is not mediated by the NTD of RCC1. This novel pathway does not require importin-α or importin-β or the addition of any other soluble factor in vitro; however, this pathway is saturable and sensitive only to a subset of inhibitors of classical import pathways. Furthermore, the nuclear import of RCC1 does not require a preexisting Ran gradient or energy. We speculate that this second import pathway evolved to ensure that RCC1 never accumulates in the cytoplasm.