REGULATION OF THE MITOSIS INHIBITING KINASE--WEEL

有丝分裂抑制激酶的调节

• 批准号: 2520478
• 负责人: MICHAEL N BODDY
• 金额: $ 2.62万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2520478
• 关键词: cell cycle; fungal genetics; protein kinase; protein structure function

The correct timing of mitosis is a critical element of the eukaryotic cell cycle. If mitosis initiates prematurely then damage to the genetic material transmitted to daughter cells can occur. Such genetic damage in multicellular organisms is a contributory factor in the initiation of cancer. This project aims to define the regulation of a key mitotic inhibitory kinase, Wee1. The regulation of Wee1 will be studied in Schizzosaccharomyces pombe, which represents an excellent model eukaryotic system for such studies. That is, the regulatory elements of fundamental processes in yeast are well conserved in man. The kinase activity(ies) responsible for inactivating Wee1 at mitosis is (are) to be identified. Cdc2 has been postulated to represent such a kinase however, preliminary data suggest that in S.pombe, Cdc2 is not a major contributor to this activity. Other potential candidates such as Plo1 or Cds1 will be tested as Wee1 inhibitory kinases. If these are excluded, the kinase activity(ies) associated with the N-terminus of Wee1 will be purified biochemically, by virtue of their affinity for GST-Wee1(N-terminus) fusion proteins. Once isolated, the kinase(s) can be rapidly tested for their roles in Wee1 and cell cycle control using yeast genetics and biochemical techniques. These studies will provide a more complete understanding of the regulation of mitosis and therefore oncogenesis.

有丝分裂的正确时机是真核生物的关键要素 细胞周期。 如果有丝分裂过早开始，则会损害遗传 可能会发生物质传递给子细胞的情况。 这样的基因损伤 在多细胞生物体中，它是启动的一个促成因素 癌症。 该项目旨在定义关键有丝分裂的调控 抑制性激酶，Wee1。 Wee1 的调控将在 Schizzosaccharomyces pombe，代表了一个优秀的模型 用于此类研究的真核系统。 也就是说，监管要素 酵母中的一些基本过程在人类中得到了很好的保存。 激酶 负责在有丝分裂时使 Wee1 失活的活动是 被识别。 Cdc2 被假定代表这样一种激酶 然而，初步数据表明，在粟酒裂殖酵母中，Cdc2 并不是主要的 本次活动的贡献者。其他潜在候选者，例如 Plo1 或 Cds1 将作为 Wee1 抑制激酶进行测试。 如果这些是 排除，与 N 末端相关的激酶活性 Wee1 将通过生化纯化，因为它们对 GST-Wee1（N 末端）融合蛋白。 一旦分离，激酶可以 使用以下方法快速测试它们在 Wee1 和细胞周期控制中的作用 酵母遗传学和生化技术。 这些研究将提供 对有丝分裂的调节有更全面的了解，因此 肿瘤发生。