Interplay between the Polo and Scant/Greatwall mitotic kinases

Polo 和 Scant/Greatwall 有丝分裂激酶之间的相互作用

• 批准号: G0501718/1
• 负责人: David Glover
• 金额: $ 201.26万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0501718%2F1
• 关键词: Interplay; between; Polo; Scant; Greatwall

Summary of Public Engagement in ScienceThe process of cell division has been highly conserved throughout evolution. This means that simple cells like yeasts use many of the same molecules to regulate cell division as do our own cells. The process whereby enzymes called protein kinases modify cellular proteins though addition of phosphates is commonly used to change the functions of proteins as cells proceed through their division cycles. This was first demonstrated by the Nobel Prize winning finding that the major cell cycle protein kinase, the cyclin dependent kinase, is so highly conserved that the human enzyme will rescue a deficiency of the corresponding enzyme in yeast cells. We use the fruit-fly, Drosophila, in our research because the cells of this multi-cellular organism have a division apparatus that closely resembles that found in human cells. Some 15 years ago we discovered two protein kinases of Drosophila, termed Polo and Aurora, that regulate the function of this division apparatus. We now know that elevated expression of the human counterparts of these two enzymes contributes to the development of tumours. Indeed inhibitors of these molecules are now being developed by pharmaceutical companies for use in cancer therapy. The present research aims for a better understanding of the roles of not only Polo kinase but also a novel mitotic kinase, Scant/Greatwall, that appears to participate in common processes as Polo. To this end we continue to use the fruit-fly as a model firstly because it offers sophisticated genetic tools for studying regulatory pathways. Secondly we are able to follow the behaviour of its division apparatus in living cells in order to study the effects of interfering with the function of individual proteins. Our findings can be rapidly translated to the regulation of cell division in human tumour cells. We anticipate that the work will lead to finding new proteins that regulate the cell division cycle, several of which might be valid targets for the future development of anti-cancer agents. In any event, an improved knowledge of the underlying biology behind the cell division process will contribute to the rational design of new agents to combat proliferative cell disease.

公众参与科学的总结细胞分裂的过程在整个进化过程中一直高度保守。这意味着像酵母这样的简单细胞使用许多与我们自己的细胞相同的分子来调节细胞分裂。当细胞进行分裂周期时，称为蛋白激酶的酶通过添加磷酸盐来修饰细胞蛋白质的过程通常用于改变蛋白质的功能。诺贝尔奖获得者的发现首先证明了这一点，即主要的细胞周期蛋白激酶（细胞周期蛋白依赖性激酶）是如此高度保守，以至于人类酶可以挽救酵母细胞中相应酶的缺陷。我们在研究中使用果蝇，因为这种多细胞生物的细胞具有与人类细胞中的分裂装置非常相似的分裂装置。大约 15 年前，我们发现了果蝇的两种蛋白激酶，称为 Polo 和 Aurora，它们调节该分裂装置的功能。我们现在知道，这两种酶的人类对应物的表达升高有助于肿瘤的发展。事实上，制药公司现在正在开发这些分子的抑制剂用于癌症治疗。本研究旨在更好地了解 Polo 激酶以及一种新型有丝分裂激酶 Scant/Greatwall 的作用，它似乎参与了与 Polo 一样的常见过程。为此，我们首先继续使用果蝇作为模型，因为它为研究调控途径提供了复杂的遗传工具。其次，我们能够追踪活细胞中分裂装置的行为，以研究干扰单个蛋白质功能的影响。我们的发现可以快速转化为人类肿瘤细胞细胞分裂的调节。我们预计这项工作将导致寻找调节细胞分裂周期的新蛋白质，其中一些可能是未来开发抗癌药物的有效靶标。无论如何，提高对细胞分裂过程背后的生物学基础的了解将有助于合理设计新药物来对抗增殖性细胞疾病。