中文摘要
细胞分裂增殖是生物界赖以存在的最基本生命活动。在细胞分裂之前,已完成基因组复制的细胞核需要去组装,核膜崩解,染色质凝聚,纺锤体装配,为细胞分裂奠定基础。有关细胞分裂起始机制和细胞核去组装的机制研究一直是国际生物学研究领域最前沿的课题,也是相关医学领域的研究基础。深入了解其分子机理,不仅对深入认识生命活动的实质有着极其重要的理论意义,同时对深入认识相关疾病的发生发展和相关药物的筛选等至关重要。我们以往在细胞增殖调控和肿瘤发生机理研究方面已做了不少开创性研究工作,在细胞分裂起始和细胞核去组装方面做了许多深入研究,获得了一些比较深入的认识,尤其在细胞分裂调控关键性蛋白激酶如CDKs、Aurora和PLK激酶等酶活性调控机制以及激酶信号传递通路研究方面取得了实质性研究进展。本项目拟在以往工作的基础上,应用自己建立的爪蟾卵非细胞体系和细胞体系等实验手段,深入研究细胞分裂起始和细胞核去组装的分子机理。
英文摘要
Cell proliferation, or the cell division cycle, is fundamental to existence of life. It is a well-coordinated process regulated by a variety of factors through distinct passways. The mitotic entry is part of this process under a well-organized and yet to be recognized mechanism, although many aspects of it have been extensively studied and found that a number of the mitotic kinases take crucial roles. Furthermore, during the mitotic entry, the cell nucleus with duplicated genomes undergoes disassembly, the nuclear envelope breaks down, the nuclear pore complex and the nuclear lamina disassemble, the chromatin condenses into chromosomes and the mitotic spindle assembles, all of which are essential for the proper cell division, although the mechanisms of these processes largely remain to be elucidated. Over the past decade, we have focused our study on the cell cycle regulation, especially on the mitotic entry and exit under the regulation of mitotic kinases such as CDKs, Auroras and PLKs and the nuclear reconstruction, and have achieved many progresses. In this study, we will focus on the mechanisms of mitotic entry and the nuclear disassembly through using the established approaches such as cell-free and in vivo systems in the lab to investigate the important signal transduction pathways and regulatory networks. The final goal of this project will be to get insight into a deep understanding of the mechanisms underlying the mitotic entry and the nuclear disassembly and contribute to the understanding of the related diseases therapy.
