中国科技核心期刊
CN:31-1600/Q
ISSN:1004-0374
“健康与疾病的免疫”国际学术研讨会通知      关于有网站冒充本刊网站的声明
《生命科学》 2011, 23(11): 1069-1075
Ran及其结合与调控蛋白在核膜装配过程中的调控作用
吕学龙,祁 燃,吕全龙,张传茂*
(北京大学生命科学学院,生物膜与膜工程国家重点实验室,细胞增殖与调控教育部重点实验室,北京 100871)
摘 要:核膜在细胞周期中呈现高度的动态性:在细胞分裂的前中期,核膜崩解并分散到细胞质中;在细胞分裂的后期,核膜开始在染色体的表面重新装配,最终形成完整的核膜结构。近期的研究发现,Ran GTP 酶、物质转运蛋白importin β、内层核膜蛋白LBR(lamin B receptor) 以及核孔复合体蛋白nucleoporins在核膜重建的过程中起关键性调控作用,并受到细胞周期调控因子p34cdc2 激酶的调节。LBR 是一个八次跨膜的膜蛋白,主要定位于内层核膜。在细胞分裂的早期,随着核膜崩解,LBR 与核膜崩解而生成的小膜泡一起分散到细胞质中;在细胞分裂的后期,通过LBR 与importin β 相互结合,含有LBR 的膜泡被importin β 携带至染色质的表面参与核膜重建。目前已知p34cdc2 激酶对LBR 与importin β 介导的核膜重建起重要调控作用。Nucleoporins 是核孔复合体主要组分。随核膜崩解,核孔复合体解聚成nucleoporins,分散到细胞质中,或结合到其他亚细胞成分上。细胞分裂后期,核孔复合体伴随核膜装配而组装。
关键词:核膜;LBR ;importin β ;Ran GTP 酶;p34cdc2 激酶
 
Ran GTPase and its binding proteins regulate the nuclear envelope assembly
LÜ Xue-Long, QI Ran, LÜ Quan-Long, ZHANG Chuan-Mao*
(The MOE Key Laboratory of Cell Proliferation and Differentiation and the State Key Laboratory of Bio-membrane and Membrane Bioengineering, College of Life Sciences, Peking University, Beijing 100871, China)
Abstract: Ran, a Ras-like nuclear GTPase, plays a pivital role in the regulataion of the nuclear envelope assembly under the cooperation of its binding proteins RanGAP1, RCC1, importins, etc.. LBR(lamin B receptor), a chromatin and lamin B binding protein in the inner nuclear membrane, targets the membrane precursor vesicles to the chromatin mediated by importin β during the nuclear envelope (NE) assembly. It was found that the aa 69-90 of LBR sequence are required to bind importin β at aa 45-462, and the binding is essential for the NE membrane precursor vesicle targeting to the chromatin. It is also demonstrated that this binding is cell cycle-regulated and dependent on the phosphorylation of LBR S71 by p34cdc2 kinase. LBR depletion by RNAi , or perturbation of the interaction of LBR with importin β, causes the NE assembly failure and abnormal chromatin decondensation of the daughter cell nuclei, leading to the daughter cell death at early G1 phase by apoptosis. importin β also targets the nuceoporins to the chromatin regulated by Ran and its binding proteins and regulators.
Key words: nuclear envelope; LBR; importin β; RanGTP; p34cdc2
 
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