Seki T, Hayashi N, Nishimoto T
Department of Molecular Biology, Graduate School of Medical Science, Kyushu University, Fukuoka.
J Biochem. 1996 Aug;120(2):207-14. doi: 10.1093/oxfordjournals.jbchem.a021400.
RCC1 is a chromosomal protein that functions as a GEF of the nuclear G protein Ran, which GTPase activity is enhanced by RNA1 located in the cytoplasm. RCC1 has no preference for GTP or GDP-bound Ran, so that GTP-Ran formation in vivo is regulated by relative concentrations of GTP/GDP and regulatory proteins interacting with RCC1, Ran, and RNA1. Proteins possessing the special Ran-binding motif have been found to be conserved in species ranging from yeasts to mammalians. The finding of RanBP2/NUP358 clearly indicates the involvement of the Ran pathway in the nuclear pore transport function, in agreement with the finding that both rcc1- and rna1- show defects in this process. However, loss of RCC1 induces premature initiation of mitosis, resulting in G1 arrest with the micronuclei possessing mitotic condensed chromosomes. How both the cell cycle and nucleocytoplasmic transport are regulated by the RCC1-Ran pathway is a major question.
RCC1是一种染色体蛋白,作为核G蛋白Ran的鸟嘌呤核苷酸交换因子(GEF)发挥作用,其GTP酶活性由位于细胞质中的RNA1增强。RCC1对结合GTP或GDP的Ran没有偏好,因此体内GTP-Ran的形成受GTP/GDP的相对浓度以及与RCC1、Ran和RNA1相互作用的调节蛋白调控。已发现具有特殊Ran结合基序的蛋白质在从酵母到哺乳动物的物种中保守。RanBP2/NUP358的发现清楚地表明Ran途径参与核孔转运功能,这与rcc1和rna1在此过程中均表现出缺陷的发现一致。然而,RCC1的缺失会诱导有丝分裂过早启动,导致G1期停滞,微核中含有有丝分裂浓缩染色体。RCC1-Ran途径如何调节细胞周期和核质运输是一个主要问题。