STUDIES ON THE CONTROL OF CELL DIVISION IN YEAST

最近对细胞周期的研究进展导致了一个统一的 细胞周期调控假说。这一假设的核心是一个 蛋白激酶在芽殖酵母中称为CDC28，在分裂酵母中和 动物细胞为Cdc2。有人提出，无论是G1期还是S期 并且G2到M相的转变被控制在 这种蛋白激酶的激活。生物分子的差异激活 不同过渡期的CDC28蛋白激酶似乎是被介导的 通过与不同类别的正调控亚单位结合 被称为周期蛋白以及其他监管因素。这款车有 很大程度上被确认为发芽和分裂酵母，很可能 对所有真核生物都有效。 酿酒酵母目前的优势是拥有许多元素 参与G1和G2控制，已确定并可由遗传基因访问 分析。此外，已有可能制备活性酵母 从纯化的CDC28蛋白激酶组分中促进 高分辨率结构和功能分析，这是 酵母系统。我们计划继续我们过去的一些途径 在目前的研究计划中进行调查。具体来说，我们希望 仔细分析纯CDC28激酶的性质，以便更好地 了解它在体内的功能是如何调节的。该法规和 我们将研究G1和有丝分裂周期蛋白的性质。一个 将共同努力寻找BOT G1和有丝分裂关键 CDC28激酶的底物。最后，一些其他监管机构 直接或间接与CDC28激酶相互作用的元件 调节其G1和有丝分裂的功能将得到鉴定。这些 包括MIHI、CKS1和CDC37。因为它的高度保守性 细胞周期控制，这一研究过程中获得的信息 可能会对包括人类在内的所有真核生物提供信息。

Recent advances in research on the cell cycle have lead to a unifying hypothesis of cell cycle control. Central to this hypothesis is a protein kinase known in budding yeast as Cdc28 and in fission yeast and animal cells as Cdc2. It has been proposed that both the G1 to S-phase and the G2 to M-phase transitions are controlled at the level of activation of this protein kinase. The differential activation of the Cdc28 protein kinase for the different transitions appears to be mediated by association with different classes of positive regulatory subunits known as cyclins as well as by other regulatory elements. This model has largely been confirmed for budding and fission yeast and it is likely to be valid for all eukaryotes. S. cerevisiae presently has the advantage of having many of the elements involved in G1 and G2 control identified and accessible to genetic analysis. Furthermore, it has been possible to prepare active yeast Cdc28 protein kinase from purified components to facilitate high-resolution structural and functional analyses, a unique feature of the yeast system. We plan to continue a number of our past avenues of investigation in the current research plan. Specifically, we wish to perform careful analysis of the properties of pure Cdc28 kinase to better understand how its functions are regulated in vivo. The regulation and properties of both G1 and mitotic cyclins will be investigated. A concerted effort will be applied to finding bot G1 and mitotic critical substrates of the Cdc28 kinase. Finally, a number of other regulatory elements that interact directly or indirectly with the Cdc28 kinase to regulate its G1 and mitotic functions will be characterized. These include MIHI,CKS1 and CDC37. Because of the highly conserved nature of cell cycle control, the information gained in the course of this research is likely to be informative for all eukaryotic organisms, including man.