NIMA PROTEIN KINASE IN MITOTIC REGULATION

有丝分裂调节中的 NIMA 蛋白激酶

• 批准号: 2444724
• 负责人: STEPHEN A OSMANI
• 金额: $ 23.48万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-07-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2444724
• 关键词: Aspergillus; DNA replication; X ray; alleles; cell cycle; cell growth regulation; cyclins; enzyme activity; gene expression; genetic promoter element; genetic regulation; genetic regulatory element; immunoprecipitation; laboratory rabbit; microinjections; molecular cloning; nucleic acid sequence; polymerase chain reaction; posttranslational modifications; protein degradation; protein kinase; protein structure function; tissue /cell culture; ubiquitin; western blottings

DESCRIPTION: The proposed experiments are designed to continue the PI's studies of the NimA protein kinase of the filamentous fungus, Aspergillus nidulans. Previous work, almost entirely from the PI's laboratory, has demonstrated that NimA is required for passage through mitosis and is regulated by complex mechanisms involving phosphorylation and degradation. There is some evidence for NimA homologues in other eukaryotes, suggesting that this kinase is generally important in the control of eukaryotic mitosis. In the present application, the PI proposes an extensive series of experiments that will address several aspects of NimA function. There are five specific aims: (1) Genetic and biochemical approaches will be used to identify proteins that interact with NimA. Significant progress has already been made toward the characterization of SonA, an extragenic suppressor of a NimA mutation. (2) The PI proposes to study the role of ubiquitination in the mitotic degradation of NimA. (3) Phosphorylation sites on NimA will be mapped and mutated to determine their role in NimA regulation. (4) The role of NimA in the S phase checkpoint will be explored. Preliminary experiments suggest that inhibition of DNA synthesis may block mitotic entry through inhibition of NimA. The proposed experiments will characterize the control of NimA gene expression by Cdc2 and the control of NimA phosphorylation by BimE, a protein also implicated in NimA control during S phase arrest. (5) Experiments are proposed to further define the precise function of NimA in mitosis, with an emphasis on its role in spindle asembly.

描述：拟议的实验旨在继续PI 丝状真菌的NIMA蛋白激酶的研究 尼杜兰人。 以前的工作几乎完全来自PI的实验室 证明Nima是通过有丝分裂所必需的，并且 受涉及磷酸化和降解的复杂机制调节。 在其他真核生物中有一些证据表明NIMA同源物，这表明 这种激酶通常在控制真核生物中很重要 有丝分裂。 在本应用中，PI提出了一系列的一系列 将解决NIMA功能的几个方面的实验。 有 五个具体目的：（1）遗传和生化方法将用于 识别与NIMA相互作用的蛋白质。 取得了重大进展 是为了表征Sona的特征 NIMA突变。 （2）PI提议研究泛素化的作用 NIMA的有丝分裂降解。 （3）NIMA上的磷酸化位点将是 映射和突变以确定其在NIMA调节中的作用。 （4）角色 将探索S相检查点中的NIMA。 初步实验 表明抑制DNA合成可能会通过 抑制NIMA。 提出的实验将表征控制 通过CDC2表达NIMA基因的表达，并控制NIMA磷酸化 Bime，一种蛋白质也与NIMA相对的蛋白质相关。 （5） 提出了实验以进一步定义NIMA的精确功能 有丝分裂的重点是它在纺锤体中的作用。