RanGTPase: A Key Regulator of Nucleocytoplasmic Trafficking.
RanGTPase: A Key Regulator of Nucleocytoplasmic Trafficking.
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DOI：
10.4255/mcpharmacol.09.19
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Huang Y
中科院分区：
文献类型：
--
作者：
Lui K;Huang Y
RanGTP酶属于小GTP酶的Ras超家族。它具有独特的酸性C-末端DEDDDL基序，主要定位于细胞核。已知RanGT β调节核质运输以及有丝分裂纺锤体和核膜形成。RAN定向的核质运输是一个能量依赖的定向过程，也依赖于核输入或输出信号。Ran-directed nucleocytoplasmic trafficking也由几种细胞组分促进，包括RanGT β、核转运蛋白、NTF 2和核孔蛋白。GTP结合的Ran不对称地分布在细胞核中，而GDP结合的Ran主要分布在细胞质中。在RanGEF和RanGAP的控制下，RanGTcycle在GDP和GTP绑定状态之间循环，使其能够以准确的空间和时间方式穿梭货物。RanGTP结合的Ran在细胞核中解离importin：cargo复合物并将importin回收到细胞质中，从而在核输入中发挥作用。同样，RanGTP酶在核输出中发挥作用，其方式为核GTP结合的Ran触发Ran：输出蛋白：货物三聚体复合物的聚集，然后将其转运至细胞质，而RanGTP水解为RanGDP在细胞质中释放输出货物。据报道，RanGT β对细胞活力至关重要，其过表达与肿瘤发生有关。因此，RanGT在调节关键细胞事件中起着至关重要的作用，其表达的改变可能导致癌症的发展和/或进展。
RanGTPase belongs to the Ras superfamily of small GTPases. It possesses a distinctive acidic C-terminal DEDDDL motif and predominantly localizes to the nucleus. RanGTPase is known to regulate nucleocytoplasmic trafficking as well as mitotic spindle and nuclear envelope formation. Ran-directed nucleocytoplasmic trafficking is an energy-dependent directional process that also depends on nuclear import or export signals. Ran-directed nucleocytoplasmic trafficking is also facilitated by several cellular components, including RanGTPase, karyopherins, NTF2 and nucleoporins. GTP-bound Ran is asymmetrically distributed in the nucleus, while GDP-bound Ran is predominantly cytoplasmic. Controlled by RanGEF and RanGAP, RanGTPase cycles between the GDP- and GTP-bound states enabling it to shuttle cargoes in an accurate spatial and temporal manner. RanGTPase plays a role in the nuclear import in such a way that GTP-bound Ran dissociates importin:cargo complex in the nucleus and recycles importin back to cytoplasm. Likewise, RanGTPase plays a role in the nuclear export in such a way that nuclear GTP-bound Ran triggers the aggregation of Ran:exportin:cargo trimeric complex which is then transported to cytoplasm while hydrolysis of RanGTP to RanGDP releases the export cargoes in cytoplasm. RanGTPase has been reported to be essential for cell viability and its over-expression is linked to tumorigenesis. Thus, RanGTPase plays a crucial role in regulating key cellular events and alterations in its expression may lead to cancer development and/or progression.