CHARACTERIZATION OF PROTEINS THAT INTERACT WITH THE CELL-CYCLE REGULATORY PROTEIN RAN/TC4
CHARACTERIZATION OF PROTEINS THAT INTERACT WITH THE CELL-CYCLE REGULATORY PROTEIN RAN/TC4
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DOI：
10.1038/366585a0
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发表时间：
1993-12-09
期刊：
影响因子：
64.8
通讯作者：
RUSH, MG
中科院分区：
文献类型：
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作者：
COUTAVAS, E;REN, MD;RUSH, MG
人类RAS相关核蛋白RAN/TC4(参考文献1-4)是一个保守的GTP酶家族的原型，它可以调节细胞周期进程5-8和信使RNA转运9。RAN被认为经历了GTP结合和水解的严格控制的循环，作为GTP酶开关10，11，其GTP和GDP结合的形式与调节器和效应器进行不同的相互作用。一种已知的调节蛋白RCC1(参考文献12，13)与RAN相互作用催化鸟嘌呤核苷酸交换，RCC1和RAN都是内在检查点控制的组成部分，可以防止过早地启动有丝分裂。为了测试和扩展GTP酶开关模型，我们搜索了RAN特异性GTP酶激活蛋白(GAP)和假定的效应因子(与RAN/TC4-GTP特异性相互作用的蛋白质)。我们报道了RAN缺口的鉴定及其用于研究突变的RAN蛋白的GTP水解性，以及RAN/TC4-GTP特异性结合蛋白的鉴定和克隆。
THE human Ras-related nuclear protein Ran/TC4 (refs 1-4) is the prototype of a well conserved family of GTPases that can regulate both cell-cycle progression5-8 and messenger RNA transport9. Ran has been proposed to undergo tightly controlled cycles of GTP binding and hydrolysis, to operate as a GTPase switch10,11 whose GTP- and GDP-bound forms interact differentially with regulators and effectors. One known regulator, the protein RCC1 (refs 12, 13), interacts with Ran to catalyse guanine nucleotide exchange, and both RCC1 and Ran are components of an intrinsic checkpoint control that prevents the premature initiation of mitosis. To test and extend the GTPase-switch model, we searched for a Ran-specific GTPase-activating protein (GAP), and for putative effectors (proteins that interact specifically with Ran/TC4-GTP). We report here the identification of a Ran GAP and its use to characterize the GTP-hydrolysing properties of mutant Ran proteins, and the identification and cloning of a binding protein specific for Ran/TC4-GTP.