Di Fiore Barbara, Ciciarello Marilena, Lavia Patrizia
CNR Institute of Molecular Biology and Pathology, Section of Genetics, University La Sapienza, Rome, Italy.
Cell Cycle. 2004 Mar;3(3):305-13. Epub 2004 Mar 1.
The Ran GTPase has important roles in nucleocytoplasmic transport, cell cycle progression, nuclear organization and nuclear envelope (NE) assembly. In this review, we discuss emerging evidence that implicate the Ran GTPase system in mitotic control in mammalian cells. Recent work indicates that members of the Ran network control two fundamental aspects of the mammalian mitotic apparatus: (i) centrosome and spindle pole function, and (ii) kinetochore function. It is also emerging that, after NE breakdown, specific Ran network components assemble in local combinations at crucial sites of the mitotic apparatus. In the light of these findings, the original notion that nucleotide-bound forms of the Ran GTPase are distributed along a unique "gradient" in mitotic cells should be re-examined. Available data also suggest that the Ran system is deregulated in certain cellular contexts: this may represent a favoring condition for the onset and propagation of mitotic errors that can predispose cells to become genetically unstable and facilitate neoplastic growth.
Ran GTP酶在核质运输、细胞周期进程、细胞核组织及核膜（NE）组装中发挥着重要作用。在本综述中，我们讨论了一些新出现的证据，这些证据表明Ran GTP酶系统参与哺乳动物细胞的有丝分裂调控。近期研究表明，Ran网络的成员控制着哺乳动物有丝分裂装置的两个基本方面：（i）中心体和纺锤体极功能，以及（ii）动粒功能。同样逐渐明确的是，在核膜破裂后，特定的Ran网络组件会在有丝分裂装置的关键部位以局部组合的形式组装。鉴于这些发现，有必要重新审视最初的观点，即Ran GTP酶的核苷酸结合形式在有丝分裂细胞中沿独特的“梯度”分布。现有数据还表明，Ran系统在某些细胞环境中失调：这可能是有丝分裂错误发生和传播的有利条件，而有丝分裂错误会使细胞易于发生基因不稳定并促进肿瘤生长。
