Bischoff F R, Klebe C, Kretschmer J, Wittinghofer A, Ponstingl H
Division for Molecular Biology of Mitosis, German Cancer Research Center, Heidelberg, Federal Republic of Germany.
Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2587-91. doi: 10.1073/pnas.91.7.2587.
The nuclear Ras-related protein Ran binds guanine nucleotide and is involved in cell cycle regulation. Models of the signal pathway predict Ran to be active as Ran.GTP at the initiation of S phase upon activation by the nucleotide exchange factor RCC1 and to be inactivated for the onset of mitosis by hydrolysis of bound GTP. Here a nuclear homodimeric 65-kDa protein, RanGAP1, is described, which we believe to be the immediate antagonist of RCC1. It was purified from HeLa cell lysates and induces GTPase activity of Ran, but not Ras, by more than 3 orders of magnitude. The Ran mutant Q69L, modeled after RasQ61L, which is unable to hydrolyze bound GTP, is insensitive to RanGAP1.
细胞核内与Ras相关的蛋白Ran结合鸟嘌呤核苷酸并参与细胞周期调控。信号通路模型预测，在核苷酸交换因子RCC1激活后，Ran在S期开始时以Ran.GTP形式处于活性状态，并在有丝分裂开始时通过结合的GTP水解而失活。本文描述了一种65 kDa的细胞核同源二聚体蛋白RanGAP1，我们认为它是RCC1的直接拮抗剂。它从HeLa细胞裂解物中纯化得到，可诱导Ran而非Ras的GTPase活性提高3个数量级以上。以不能水解结合的GTP的RasQ61L为模型构建的Ran突变体Q69L对RanGAP1不敏感。
