COACTIVATION OF RANGTPASE AND INHIBITION OF GTP DISSOCIATION BY RAN GTP-BINDING PROTEIN RANBP1
COACTIVATION OF RANGTPASE AND INHIBITION OF GTP DISSOCIATION BY RAN GTP-BINDING PROTEIN RANBP1
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DOI：
10.1002/j.1460-2075.1995.tb07049.x
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发表时间：
1995-02-15
期刊：
影响因子：
11.4
通讯作者：
PONSTINGL, H
中科院分区：
文献类型：
--
作者：
BISCHOFF, FR;KREBBER, H;PONSTINGL, H
RCC1（染色体凝聚的调节剂）刺激Ras相关的核蛋白Ran上的鸟嘌呤核苷酸解离。两种多肽都是涉及调节DNA复制、有丝分裂的开始和退出、mRNA加工和运输以及蛋白质输入到核中的调节途径的组分。在寻找RCC 1- Ran信号途径的其他成员时，我们已经鉴定了23、45和300 kDa的蛋白质，其与Ran-GTP紧密结合，但不与Ran-GDP紧密结合。纯化的可溶性23 kDa Ran结合蛋白RanBP 1不激活RanGTP酶，但使由RanGTP酶激活蛋白RanGAP 1诱导的GTP水解增加一个数量级。在不存在RanGAP的情况下，它强烈抑制RCC 1诱导的Ran结合GTP的交换。此外，它与无核苷酸的RCC 1-Ran形成稳定的复合物，由于这些性质，它与鸟嘌呤二磷酸解离抑制剂明显不同，鸟嘌呤二磷酸解离抑制剂优先阻止蛋白结合的GDP的交换，并且在某些情况下显示出抑制GAP诱导的GTP水解。RanBP 1是调节Ras相关蛋白对GTP的结合和水解的新蛋白质类的第一个成员。
RCC1 (the regulator of chromosome condensation) stimulates guanine nucleotide dissociation on the Ras-related nuclear protein Ran, Both polypeptides are components of a regulatory pathway that has been implicated in regulating DNA replication, onset of and exit from mitosis, mRNA processing and transport, and import of proteins into the nucleus, In a search for further members of the RCC1- Ran signal pathway, we have identified proteins of 23, 45 and 300 kDa which tightly bind to Ran-GTP but not Ran-GDP, The purified soluble 23 kDa Ran binding protein RanBP1 does not activate RanGTPase, but increases GTP hydrolysis induced by the RanGTPase-activating protein RanGAP1 by an order of magnitude, In the absence of RanGAP, it strongly inhibits RCC1-induced exchange of Ran-bound GTP. In addition, it forms a stable complex with nucleotide-free RCC1-Ran, With these properties, it differs markedly from guanine diphosphate dissociation inhibitors which preferentially prevent the exchange of protein-bound GDP and in some cases were shown to inhibit GAP-induced GTP hydrolysis, RanBP1 is the first member of a new class of proteins regulating the binding and hydrolysis of GTP by Ras-related proteins.